AML - CR1

1
BASSO GRADO A piccoli linfociti B follicolare,
prevalentemenete a piccole cellule clivate C
follicolare misto, piccole cellule clivate e
grandi cellule
GRADO INTERMEDIO D follicolare, prevalenza di
grandi cellule E diffuso, a piccole cellule
clivate F diffuso, misto a piccole e grandi
cellule G diffuso a grandi cellule
ALTO GRADO H immunoblastico I linfoblastico J
piccole cellule non clivate (burkitt)
2
Table 1. International Lymphoma Study Group
Classification
T/NK-Cell Lymphoma Precursor T-lymphoblastic T-cel
l chronic lymphocytic leukemia Large granular
lymphocyte leukemia Mycosis fungoides Peripheral
T cell, unspecified Medium-sized Mixed medium
and large cell Large cell Lymphoepithelioid Hepato
splenic Subcutaneous panniculitic Angioimmunoblast
ic Angiocentric, nasal Intestinal Adult T-cell
lymphoma/leukemia Anaplastic large cell
(including null phenotype) Anaplastic large cell,
Hodgkins-like Unclassifiable low
grade Unclassifiable high grade
B-Cell Lymphoma Precursor B-lymphoblastic Small
lymphocytic (CLL) Lymphoplasmacytic Mantle
cell Follicle center, follicular Grade 1 Grade
2 Grade 3 Follicle center diffuse, small
cell Marginal zone B-cell, MALT type Marginal
zone B-cell, nodal Marginal zone B-cell,
splenic Hairy cell leukemia Plasmacytoma Diffuse
large B-cell Diffuse mediastinal large
B-cell Burkitts High grade B-cell,
Burkitt-like Unclassifiable low
grade Unclassifiable high grade
Blood, Vol 89, No 11 (June 1), 1997 pp 3909-3918
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International Prognostic Index
(I.P.I.) Fattore assente presente stadio I-I
I III-IV LDH normali elevate performance
status 0-1 2 o gt Categoria - rischio RC
OS 5 anni basso 0 92 83 int.
basso 1 78 69 int. alto 2 57 46 alto 3
46 32
Shipp et al., NEJM 329, 387-394. 1993
4
Shipp N Engl J Med 329, 987, 1993
OS and IPI Age adjusted index, patients lt 69 (n
1274)
28-2-99
SONO TROPPPO BASSE
5
Shipp N Engl J Med 329, 987, 1993
OS and IPI Age adjusted index, patients lt 69 (n
1274)
SONO TROPPPO BASSE
28-2-99
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Fisher
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EFS
Fisher RI, et al. New Engl J Med 328, 1002, 1993
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Overall survival
Fisher RI, et al. New Engl J Med 328, 1002, 1993
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Gianni
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De vita, NEJM review Hodgkin
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Philip
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Philip T. et al. New Engl J Med 333, 1540, 1995
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Philip T. et al. New Engl J Med 333, 1540, 1995
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Haioun
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Survival benefit of High-Dose Therapy in
Poor-Risk Aggressive Non-Hodgkins Lymphoma
Final Analysis of the Prospective LNH87-2
Protocol A Groupe dEtude des Lymphomes de
lAdulte Study Haioun C, Lepage E, Gisselbrecht
C et al. J Clin Oncol 18, 3025, 2000
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LNH87-2 median follow-up of 8 years final
analysis randomized study - consolidative
sequential CHT (ifosfamide, etoposide,
asparaginase, and cytarabine) vs - HDT
using cyclophosphamide, carmustine, and etoposide
(CBV regimen) followed by stem-ceIl
transplantation
Haioun C., et al. J Clin Oncol 18, 3025, 2000
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• in patients with
• aggressive NHL
• in first complete remission after induction
• higk/intermediate and high-risk patients
  identified by the age-ad justed internationai
  prognostic index.

Haioun C., et al. J Clin Oncol 18, 3025, 2000
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916 eligible patients
451 with two or three risk factors.
277 (61) reached complete remission 236
randomized
125 patients HDT
111 sequential CHT
Haioun C., et al. J Clin Oncol 18, 3025, 2000
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8 year OS ABMT 64 (95 CI 55-73) CHT 49 (95
CI 39-59)
Haioun C., et al. J Clin Oncol 18, 3025, 2000
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8 year DFS ABMT 55 (95 CI 46-64) CHT 39
(95 CI 30-48)
ABMT
CHT
Haioun C., et al. J Clin Oncol 18, 3025, 2000
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Conclusion On the basis of the final analysis
of this prospectively treated series of patients,
retrospectively analyzed on the basis of the
International Prognostic Index, we hypotesize
that HDT benefits patients at higher risk who
achieve complete remission after induction
treatment
Haioun C., et al. J Clin Oncol 18, 3025, 2000
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T - cell
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Peripheral T-CeII Lymphoma - - JAMES O. ARMITAGE
MD, JOHN P GREER. MD.t ALEXANDRA M. LEViNE.
MDDENNIS D. WEISENBURGER. MD. SILVIA C.
FORMENTI, MD. MAWT1N BAST. BS?, SUE CONLEY, BA.
JENE PIERSON. BS, JAMES UNDER. MD, JOHN B.
COUSAR. MD AND BHARAT N. NATHWANI, MD Cancer
63158-163, 1989.
Clinical data were reviewed from 134 cases of
peripheral T-cell lymphoma diagnosed in three
centers. The median age of the patients was 57
years (range, 4-97 yasrs), 59 were male, and 36
patients (27) had a history of a preceeding
disorder of the immune system. The tumors were
grooped histologically into large cell (43),
mixed large and small cell (40), sud small cell
(17). The stage at diagnosis was I(7), II
(21), III (22), and IV (50). B symptoms were
present in 57. The most frequent sites of
extranodal involvement were bone marrow (35),
skin (13), and lung (11). Eighty patients were
treated with a multiagent chemotherapy regimen
with proven curative potential in aggressive
non-Hodgkins lymphomas and the remainder of the
patients received less intensive chemotherapy (36
patients), radiotherapy (9 patients), or no
treatment (9 patients). Fifty percent of the
Intensively treated patients achieved complete
remission and the actuarial 4-years survival was
45. However, the 4-year disease free survival in
patients with Stage IV disease was only 10.
Although peripheral T-cell lymphomas appeared
similar in many ways to their B-cell counterpart,
disease-free survival by stage was low and
patients with Stage IV disease had an especially
poor outlook.
41
Armitage, Cancer 63158-163, 1989.
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Table 3. Distribution of NHL Cases by the
Consensus Diagnosis Diffuse large
B-cell 422 30.6 Follicular 304
22.1 Marginal zone B-cell, MALT 105 7.6
Peripheral T-cell 96 7.0 Small
B-lymphocytic (CLL) 93 6.7 Mantle
cell 83 6.0 Primary mediastinal large
B-cell 33 2.4 Anaplastic large
T/null-cell 33 2.4 High grade B-cell,
Burkitt-like 29 2.1 Marginal zone B-cell,
nodal 25 1.8 Precursor T-lymphoblastic 23 1.
7 Lymphoplasmacytoid 16 1.2 Marginal zone
B-cell, splenic 11 lt 1 Mycosis
fungoides 11 lt 1 Burkitts 10 lt 1
Blood, Vol 89, No 11 (June 1), 1997 pp 3909-3918
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Table 6. Patient Characteristics by Histologic
Type Median Stage Marr PI PI 5-yr
5-yr Diagnosis Male Age 1 or 2 Pos
0/1 4/5 OAS FFS Follicular, all grades
42 59 33 42 39 6 72 40 Mantle
cell 74 63 19 63 19 19 27 11 Marginal zone
B-cell, MALT 45 61 66 14 38 5 74 60 Marginal
zone B-cell, nodal 41 58 18 41 36 9 57 29 Small
lymphocytic 53 65 6 73 17 10 51
25 Lymphoplasmacytoid 53 63 20 73 20 13 59 25 Dif
fuse large B-cell 55 64 51 17 31 16 46 41 Primary
mediastinal large B-cell 34 37 66 3 44 9 50 48 Bur
kitts 89 31 56 33 44 22 44 44 Burkitt-like 59 55
50 21 25 18 47 43 T-lymphoblastic 74 25 13 43 35
22 26 24 Peripheral T-cell, all
types 56 61 18 37 14 27 25 18 Anaplastic large
T/ null-cell 69 33 50 12 50 19 77 58
Blood, Vol 89, No 11 (June 1), 1997 pp 3909-3918
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Table 7. Survival by Histologic Type and the
International Prognostic Index immunologic data.
For other types, such as the lymphoplas-macytoid,
nodal marginal zone B-cell, and high-grade B-cell
5-yr OAS 5-yr FFS Burkitt-like lymphomas,
imprecise histologic criteria and the Index Index
Index Index lack of specific immunologic markers
led to a diagnostic Consensus Diagnosis 0/1 4/5
0/1 4/5 accuracy of only 53 to 65. Further
definition of these Follicular, all grades 84 17
55 6 entities is clearly needed. Because the need
for immunophe- Mantle cell 57 0 27 0 notyping
cannot be predicted before biopsy, it is vital
that Marginal zone B-cell, MALT 89 40 83 0 each
patient have tissue available for
immunophenotyping Marginal zone B-cell, nodal 76
50 30 0 and other special studies to facilitate
proper patient care. In Small lymphocytic (CLL)
76 38 35 13 many cases, this will require
communication between the Diffuse large B-cell 73
22 63 19 oncologist, the surgeon, and the
pathologist. Primary mediastinal large B-cell 77
0 69 0 The 13 major types of NHL shown in Fig 1
made up over High grade B-cell, Burkitt-like 71 0
71 0 Precursor T-lymphoblastic 29 40 29 40 90 of
the cases in our study, with diffuse large
B-cell Peripheral T-cell, all types 36 15 27 10
lymphoma and follicular lymphoma comprising over
50 Anaplastic large T/null-cell 81 83 49 83 of
the cases and the newly recognized entities
comprising 21 of the cases (Table 3). The
clinical features of the Abbreviations PI,
International Prognostic Index OAS, overall
sur-vival FFS, failure-free survival CLL,
chronic lymphocytic leukemia. various lymphoma
types were remarkably different, as were
Blood, Vol 89, No 11 (June 1), 1997 pp 3909-3918
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MACOP-B vs ProMACE-MOPP in the treatment of
advanced diffuse NHL results of a prospective
randomized trial by the non-Hodgkin's Lymphoma
Cooperative Study Group. ProMACE-MOPP MACOP-B
CR 49.1 52.3 3-year OS 45.2 52.3 3
-yearPFS 36.4 36.1 CONCLUSION No
significant differences in terms of efficacy
and/or toxicity between ProMACE-MOPP and MACOP-B
are evident. These results are consistent with
recent randomized trials showing that the
new-generation aggressive regimens are no better
than previous ones.
Sertoli-MR et-al J-Clin-Oncol. 1994 12(7) 1366
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Follicular low grade lymphoma
Patients No 91 5 years survival 66 median
overall survival 111 months 5
years survival sex male 57 female 73 0.0
3 age lt 70 67 gt 70 28 0.004 Stage I
or II 89 III or IV 57 0.06 B
symptoms yes 41 no 69 0.03
Morel et al., Ann Hematol 66, 303, 1993
70
Intermediate/ high-grade lymphomasresponse rate
treatment No O.R. C.R CHOP 225
80 44 m-BACOD 223 82 48 Pro-MACE-C
ytaBOM 233 87 56 MACOP-B 218 83 51
Fisher et al, NEJM 328, 1002, 1993
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Intermediate/ high-grade lymphomasresponse rate
treatment No O.R. C.R CHOP 225
80 44 m-BACOD 223 82 48 Pro-MACE-C
ytaBOM 233 87 56 MACOP-B 218 83 51
Fisher et al, NEJM 328, 1002, 1993
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Intermediate/ high-grade lymphomas3 years
overall survival
treatment No CHOP 225 54 m-BACO
D 223 52 P0.9 Pro-MACE-CytaBOM 233 50 M
ACOP-B 218 50
Fisher et al, NEJM 328, 1002, 1993
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Intermediate/ high-grade lymphomas3 years
overall survival
treatment No CHOP 225 54 m-BACO
D 223 52 P0.9 Pro-MACE-CytaBOM 233 50 M
ACOP-B 218 50
Fisher et al, NEJM 328, 1002, 1993
74
Intermediate/ high-grade lymphomas3 years D.F.S.
treatment No CHOP 225 41 m-BAC
OD 223 46 P0.35 Pro-MACE-CytaBOM 233 46
MACOP-B 218 41
Fisher et al, NEJM 328, 1002, 1993
75
Intermediate/ high-grade lymphomas3 years D.F.S.
treatment No CHOP 225 41 m-BAC
OD 223 46 P0.35 Pro-MACE-CytaBOM 233 46
MACOP-B 218 41
Fisher et al, NEJM 328, 1002, 1993
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Abstract 575 (EBMT) Allogeneic stem cell
transplantation for advanced hodgkin's disease
The M.D. Anderson experience P. Anderlini, B.
Andersson, J. Gajewski, S. Giralt, R. Mehra, D.
Claxton, N. Ueno, I. Khouri, D. Przepiorka, M.
Donato, M. Körbling, R. Champlin M.D. Anderson
Cancer Center, Houston, USA Since 1989 a total
of nine allogeneic bone marrow (alloBMT) or blood
stem cell transplantation (alloSCT) for
relapsed/refractory Hodgkin's disease (HD) from
HLA-identical related donors have been performed
at MDACC. The results are as follows
89
Time period 1989-1996 1996-present Stem cell
source AlloBMT (n 5) AlloSCT (n 4). Median
patient age (yrs) 27 (23-41) 30
(21-35) Conditioning regimen CBV (n 3),
Bu-Cy (n 3), Bu-Cy (n 2) other (n
1) Status at transplant Refr (n 1) Rel 2 or
3 (n 4) rel 2/3 (n 2), other (n
2) Prior autologous BMT 4/5 3/4 Outcome Expir
ed 5/5 Alive 4/4 (4 within 6 mos) (2 in
remission) Median follow-up (mos) n.a. 7
(2-10) P. Anderlini, e t al. EBMT 1998
90
The causes of death in the alloBMT pts. were
relapse (n 1), transplant-related mortality
(TRM) (n 3) and unknown (n 1). Conclusions
(1) As reported in the literature (mainly from
registry data), alloBMT in relapsed/refractory HD
was associated with high TRM and relapse rates.
(2) The reason for the seemingly improved early
TRM and short-term outcome recently seen in
allografted HD patients at MDACC is unclear.
Several factors, such as better supportive care,
FK506-based GVHD prophylaxis and possibly the
introduction of alloSCTs and IV busulfan may be
responsible for this very encouraging trend. P.
Anderlini, e t al. EBMT 1998
91
patients number 42 median age 33
(16-56) follicular large cell 6 diffuse
mixed 5 diffuse large cell 21 immunoblastic 10
stage III-IV 37 (88) bulky gt 8 cm 36
(86) IPI High 25 (60) IPI HI 17 (40)
Nademanee, Blood 90, 3844, 1997
92
standard intensive n. 34 33 median
age 49 (19-60) 37 (23-60) centroblastic 18
19 immunoblastic 2 1 T cell 4 3 unclassifi
ed 5 8 Ki-1 3 1 other 2 1 bulky 2
2/34 18/33 stage IV 27/34 25/33 adverse
features 2 23/34 15/33 adverse features
3 11/34 18/33
Pettengel J Clin Oncol 14, 586, 1996
93
standard intensive number 60 61 median
age 49(19-60) 45 (18-60) large cleaved
(G) 37 37 l.c. with LG component 5 6 immunobl
astic 16 7 anaplastic 2 11 stage
II 17 18 stage III-IV 43 43 bulky gt
10cm 26 31 bone marrow 10 15 adverse
features 0-1 16 23 adverse features 2-3 44 38
Cortelazzo Br J Haematol 99, 379, 1997
94
CHOP m-BACOD ProMACE MACOP-B CytaBOM nu
mber 225 223 233 218 age (median) 56
(15-79) 57 (18-81) 54 (17-81) 57 (19-79)
gt65 26 25 27 24 Bulky 40 41 41 40 Ma
rrow 25 26 27 27 LDH gt250
45 43 42 43 WF group D-E 14 15 15 14
F-G-H 81 82 81 82 J 5 4 4 4
Fisher, NEJM 328, 1002, 1993
95
standard (50) intensive (48) age 35
(17-60) 34 (18-59) group G 88 91 group
H 12 10 T cell 0 0 stage
I-II 32 28 stage III-IV 68 72 Marrow 0
0 Bulky 70 76 IPI L-IL 2 0 IPI
HI-H 74 94
Gianni et al, NEJM 336, 1290, 1997
96
TI Comparison of a second-generation
combination chemotherapeutic regimen (m-BACOD)
with a standard regimen (CHOP) for advanced
diffuse non-Hodgkin's lymphoma AU Gordon-LI
Harrington-D Andersen-J Colgan-J Glick-J
Neiman-R Mann-R Resnick-GD Barcos-M
Gottlieb-A et-al AD Northwestern University
Medical School, Department of Medicine, Chicago,
IL 60611. SO N-Engl-J-Med. 1992 Nov 5
327(19) 1342-9 AB In 1984, the Eastern
Cooperative Oncology Group began a randomized
controlled clinical trial of patients with
advanced (stage III or IV) diffuse mixed or
diffuse large-cell lymphoma to determine whether
complete-remission rates, survival, and toxicity
differed when patients were treated with CHOP as
compared with m-BACOD.
97
From July 1984 through January 1988, 392 patients
were enrolled. After a median follow-up of four
years, there were no significant differences in
rates of complete remission, time to treatment
failure, disease-free survival, or overall
survival in the patients treated with CHOP as
compared with those treated with m-BACOD.
However, there was more severe and
life-threatening pulmonary, infectious, and
hematologic toxicity associated with the m-BACOD
regimen. CONCLUSIONS. For patients with stage
III or IV diffuse mixed or diffuse large-cell
lymphoma, CHOP is superior to m-BACOD.
Gordon-LI et al. N-Engl-J-Med. 1992 Nov 5
327(19) 1342-9
98
TI Randomized comparison of MACOP-B with CHOP
in patients with intermediate-grade non-Hodgkin's
lymphoma. The Australian and New Zealand Lymphoma
Group. AU Cooper-IA Wolf-MM Robertson-TI
Fox-RM Matthews-JP Stone-JM Ding-JC Dart-G
Matthews-J Firkin-FC et-al AD Department
of Haematology and Medical Oncology, Peter
MacCallum Cancer Institute, Melbourne, Victoria,
Australia. SO J-Clin-Oncol. 1994 Apr 12(4)
769-78 Between October 1986 and June 1991, 304
patients were randomized to compare complete
response rates, time to failure, survival, and
toxicity for patients with intermediate-grade NHL
treated with CHOP versus those treated with
MACOP-B, in a multicenter, randomized controlled
trial performed by 22 centers of the Australian
and New Zealand Lymphoma Group (ANZLG).
99

• RESULTS
• There was no significant difference in complete
  response rates (51 for MACOP-B v 59 for CHOP),
  failure-free survival, or overall survival in the
  two treatment arms.
• Toxicity was significantly more severe with
  MACOP-B.
• CHOP remains the standard chemotherapy for this
  disease, against which all new regimens should be
  compared.

Cooper-IA et al. J-Clin-Oncol. 1994 Apr 12(4)
769-78
100
CASISTICA

CASISTICA

• Pazienti 17
• sesso
• maschi 9
• femmine 8
• Età
• media 39 (20-58)
• mediana 41

• Stato al trapianto
• RC 1 10
• RP 5
• Recidiva gt2 2
• Patologia
• LNH 11
• MdH 2
• LLA 2
• LMA 1
• MM 1

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PATOLOGIE
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TI Benefit of autologous bone marrow
transplantation over sequential chemotherapy in
poor-risk aggressive non-Hodgkin's lymphoma
updated results of the prospective study LNH87-2.
Groupe d'Etude des Lymphomes de l'Adulte. AU
Haioun-C Lepage-E Gisselbrecht-C Bastion-Y
Coiffier-B Brice-P Bosly-A Dupriez-B
Nouvel-C Tilly-H Lederlin-P Biron-P Briere-J
Gaulard-P Reyes-F AD Hopital Henri Mondor,
Creteil, France. SO J-Clin-Oncol. 1997 Mar
15(3) 1131-7 PURPOSE To compared consolidative
sequential treatment (ifosfamide, etoposide,
asparaginase, and cytarabine) versus the
high-dose regimen of cyclophosphamide,
carmustine, and etoposide (CBV) followed by
autotransplantation in patients with aggressive
non-Hodgkin's lymphoma in first complete
remission.
104
541 patients in complete remission were assigned
to receive consolidation by either sequential
chemotherapy (n 273) or autotransplant (n
268). In the higher risk population 5 years
estimated DFS OS CBV 59
65 CHT 39 52 P .01 P
.06 CONCLUSION Dose-intensive consolidation
therapy should be considered for patients at
higher risk who achieve complete remission after
induction treatment. Haioun-C et
al-J-Clin-Oncol. 1997 Mar 15(3) 1131-7
105
TI Single and double autotransplants for
relapsing/refractory Hodgkin's disease results
of two consecutive trials. AU Ahmed-T
Lake-DE Beer-M Feldman-EJ Preti-RA Seiter-K
Helson-L Mittelman-A Kancherla-R Ascensao-J
Akhtar-T Cook-P Goldberg-R Coleman-M AD
Division of Oncology and Hematology, New York
Medical College, Valhalla 10595, USA. SO
Bone-Marrow-Transplant. 1997 Mar 19(5) 449-54
AB Patients with refractory disease were
offered a second transplant with different
conditioning in the absence of progression or
excessive toxicity. 45 refractory patients (24
with primary refractory disease and 21 with
refractory relapse) received a second cycle.
After the first cycle , 12 were in CR and 11 in
PR and 10 of these 11 in PR achieved a durable CR
with the second transplant.
106

• The CR rate is 37 in patients with refractory
  relapse and 19 in those with primary refractory
  disease.
• At a median follow-up of 4 years, median survival
  is 45 months.
• Progression-free survival of the refractory
  patients who could receive a second cycle was
  similar to that of patients with sensitive
  disease.
• Conclusion
• A sequential transplant strategy is feasible.
• A subgroup of patients with refractory disease
  can achieve long-term survival after sequential
  BMT.
• Ahmed-T et al. Bone-Marrow-Transplant. 1997 Mar
  19(5) 449-54

107
BEC-2 BCNU 400 mg/m2 day -5 VP-16 1800 mg/m2
day -5 cyclophosphamide 2500 mg /m2 days -5 and
-4 TMJ Thiotepa 250 mg/m2 days -7, -6,
-5 Mitoxantrone 40 mg/m2 day -7 Carboplatin
330 mg/m2 days -7, -6, -5 Ahmed-T et al.
Bone-Marrow-Transplant. 1997 Mar 19(5) 449-54
108
CONDIZIONAMENTO

REGIME DI CONDIZIONAMENTO

• BEAM 12
• CBV 1
• BuCy 1
• MTM 2
• HD L-PAM 1

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RISULTATI

• ATTECCHIMENTO 17/17 (100)
• VIVI 17/17 (100)
• in remissione 15/17
• in recidiva 2/17 (12)
• T.R.M. 0/17 (0)
• Follow-up
• media 5 mesi (1-10)
• mediana 5 mesi

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Linfomi
- conta CD34 - colonie - citogenetica -
diagnostica molecolare
diagnosi
CHOP 4 cicli
Cy 4gr/m2 G-CSF
HD CHT (BEAM)
PBPCs
reinfusione
- criopreservazione
111
NHL INTERMEDIATE/HIGH GRADEAUTOGRAFTING
PFS
100
CR 1 n 563
63
80
60
40
CR 2 n 472
36
20
years
1
2
3
4
5
6
7
8
EBMT registry 1995
112
NHL at relapsedisease free survival

80
60
40
sensitive relapse
20
resistant relapse
1
2
3
4
5
6
7
8
years after transplantation
113
Trapianto Autologo

• Perché nei linfomi?

114
TI Autologous bone marrow transplantation in
poor-prognosis intermediate-grade and high-grade
B-cell non-Hodgkin's lymphoma in first remission
a pilot study. AU Freedman-AS Takvorian-T
Neuberg-D Mauch-P Rabinowe-SN Anderson-KC
Soiffer-RJ Spector-N Grossbard-M Robertson-MJ
et-al AD Division of Tumor Immunology,
Dana-Farber Cancer Institute, Boston, MA 02115.
SO J-Clin-Oncol. 1993 May 11(5) 931-6
115
AB Twenty-six patients with advanced-stage
diffuse intermediate/high-grade B-cell NHL
(including 16 patients with diffuse small
cleaved-cell DSC) were selected at presentation
by histologic and clinical characteristics to
have less than a 25 probability of long-term DFS
with conventional treatment. After induction
chemotherapy, 16 patients were in complete
remission (CR) and 10 were in a minimal disease
state. Patients were then treated with high-dose
cyclophosphamide, total-body irradiation (TBI),
and anti-B-cell monoclonal antibody-purged ABMT.
Freedman-AS et al. , J-Clin-Oncol. 1993 May
11(5) 931-6
116

• RESULTS
• no acute in-hospital treatment deaths occurred.
• The median follow-up period for the 21 patients
  who are alive and disease-free is 32 months.
• The DFS rate is estimated to be 85 at 28 months
  and thereafter.
• CONCLUSION This pilot study suggests that
  consolidation of first remission with ABMT may
  improve the long-term DFS rate for diffuse
  intermediate/high-grade NHL patients at high risk
  for relapse.
• Freedman-AS et al. , J-Clin-Oncol. 1993 May
  11(5) 931-6

117
A phase II multicenter trial of high-dose
sequential chemotherapy and peripheral blood stem
cell transplantation as initial therapy for
patients with high-risk non-Hodgkin's lymphoma.
Schenkein-DP et al. (Tupper Research
Institute, New England Medical Center, Boston,
MA, USA). Biol-Blood-Marrow-Transplant. 1997
Oct 3(4) 210-6
118
Thirty-two patients with high-risk NHL (defined
by the age-adjusted international index)
underwent HDS chemotherapy followed by PBSC
transplantation. HDS consisted of Phase I
(adriamycin, vincristine, and prednisone) Phase
II (cyclophosphamide, filgrastim G-CSF, and
PBSC harvest) Phase III (methotrexate,
leucovorin, vincristine Phase IV (etoposide,
filgrastim G-CSF) and Phase V (mitoxantrone,
melphalan, autologous peripheral blood stem cell
infusion, and filgrastim G-CSF). Radiation
therapy was given to sites of previous bulk
disease, 2400 cGy, (D 30-100). Schenkein-DP
et al. Biol-Blood-Marrow-Transplant. 1997 Oct
3(4) 210-6
119
TRM 6.25 median follow-up 18.8 months
(4-44) OS at 18 months 78 (95 CI 37-90) RFS
at 18 months 67 (95 CI 46-88) High-dose
sequential chemotherapy with initial PBSC
transplantation is well tolerated and appears
effective in high-risk NHL. Superior results were
noted in patients with intermediate grade versus
those with small noncleaved or lymphoblastic NHL.
Schenkein-DP et al. Biol-Blood-Marrow-Transplant.
1997 Oct 3(4) 210-6
120
TI Autotransplantation for relapsed or
refractory non-Hodgkin's lymphoma (NHL)
long-term follow-up and analysis of prognostic
factors. AU Rapoport-AP et. al. AD
Department of Medicine, University of Rochester,
School of Medicine and Dentistry, NY, USA. SO
Bone-Marrow-Transplant. 1997 May 19(9) 883-90
121
AB One hundred and thirty-six patients
autografted for relapsed or refractory
non-Hodgkin's lymphoma (NHL) were evaluated to
assess long-term event-free survival and to
identify important prognostic factors. Patients
were treated with 1-3 cycles o DHAP or other
regimens until a complete response was obtained
or there was no significant change and riceived
high-dose therapy (primarily carmustine (BCNU),
etoposide, cytarabine, and cyclophosphamide
(BEAC)) followed by unpurged autologous stem
cell rescue. Rapoport-AP et. al.
Bone-Marrow-Transplant. 1997 May 19(9) 883-90
122
TRM 4.4. 5-year EFS 34 (95 CI
24-44) median FU 3 years (range 0-7.5
years). New strategies are needed to reduce
the high rate of relapse (50-60) following
auto-transplantation for relapsed or refractory
NHL.
Rapoport-AP et al. Bone-Marrow-Transplant. 1997
May 19(9) 883-90
123
TI Primary diffuse large B-cell lymphoma of
the mediastinum outcome following high-dose
chemotherapy and autologous hematopoietic cell
transplantation. AU Sehn-LH Antin-JH
Shulman-LN Mauch-P Elias-A Kadin-ME Wheeler-C
AD Hematology-Oncology Division, Brigham and
Women's Hospital, Boston, MA, USA. SO Blood.
1998 Jan 15 91(2) 717-23 AB We performed a
retrospective analysis of 35 patients with
primary diffuse large B-cell lymphoma of the
mediastinum treated with high-dose
cyclophosphamide, carmustine, and etoposide (CBV)
plus autologous hematopoietic cell
transplantation to determine outcome and
prognostic features for progression-free survival
(PFS).
124
Patients transplanted in first response had an
estimated 5-year PFS rate of 83, compared with
58 and 27 for primarily refractory and relapsed
patients, respectively (P .02). The strongest
predictor of PFS was chemotherapy responsiveness
immediately before transplantation.
Sehn-LH et al., Blood. 1998 Jan 15 91(2)
717-23
125
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126
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129
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130
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131
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132
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133
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135
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136
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137
AGGRESSIVE REAL Working Formulation Kiel Li
neage Follicular center D. Follicular Centrobla
stic B (grade III) predominantly (follicular)
large cell Mantle cell E Diffuse small
Centrocytic B cleaved cells F. Diffuse
mixed small and large cell Diffuse large G.
Diffuse large Centroblastic B B-cell
cell (diffuse) H. Large
cell immunoblastic Primary mediastinal G.
Diffuse large Large cell. B (thymic) B
cell cell sclerosing B cell
lympohoma of mediastinum
138
AGGRESSIVE REAL Working Formulation Kiel L
ineage Peripheral F. Diffuse mixed Lymphoepitel
iod, T-cell small and large cell pleiomorphic
(small. T G. Diffuse large cell medium
or H. Large cell large cell) immunoblastic
Angioimmunoblastic Angioimmunoblastic T T
cell Adult T cell Pleiomorphic T lymphoma/le
ukemia (small, medium or large cell HTLV
) Angiocentric Pleiomorphic T Intestinal T
cell (small, medium or large cell
139
AGGRESSIVE REAL Working Formulation Kiel L
ineage Anaplastic H. Large cell Large cell T
(70) large cell immunoblastic anaplastic null
(30) (Ki-1) Lymphoblaastic I.
Lymphoblastic Lymphoblastic T (90) lymphoma
B (10) Lymphoblastic Leukemia Burkitts
J. Small non cleaved Burkitts B (95)
cell Burkitts T (5)
140
HDT auto HSCs prolunga il DFS (studi
randomizzati)

• NHL at relapse (Philip et al., N Eng l J Med 333,
  1540, 1995)
• AML RC1 (Zittoun et al., N Engl J Med 332, 217,
  1995)
• MM at diagnosis (Attal et al., N Engl J Med 335,
  91, 1996)
• NHL at diagnosis (Gianni) N Engl J Med 336, 1290,
  1997

141
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142
TI Chlorambucil/prednisone vs. CHOP in
symptomatic low-grade non-Hodgkin's lymphomas a
randomized trial from the Lymphoma Group of
Central Sweden. AU Kimby-E Bjorkholm-M
Gahrton-G Glimelius-B Hagberg-H Johansson-B
Johansson-H Juliusson-G Jarnmark-M
Lofvenberg-E et-al AD Dept of Medicine,
Danderyd Hospital, Sweden. SO Ann-Oncol.
1994 5 Suppl 2 67-71 AB Two hundred
fifty-nine previously untreated patients with
low-grade non-Hodgkin's lymphomas (NHLs), Ann
Arbor stages III and IV, entered a randomized
multicenter trial comparing the therapeutic
effect of chlorambucil/prednisone (ChP) vs. CHOP.
All patients had symptomatic disease.
143
ChP CHOP N. 132 127 R.R. (CRPR at 8
months) 36 60 p lt 0.01 3 -year
survival 59 64 n.s. 5-year
survival 41 44 n.s. corrected 5-year
survival 49 54 n.s. median survival
months 46 52 n.s. After correction for
intercurrent deaths Kimby-E et al., Ann-Oncol.
1994 5 Suppl 2 67-71
144
The median survival time from diagnosis was 68
months, with no differences between the treatment
groups. In all histological subgroups (CLL, IC,
CC, and CB-CC), a higher remission rate was seen
with the CHOP regimen but with no statistically
significant influence on survival. Comparing
patients below and above 65 years of age, no
significant difference in survival was noted
between the two treatment groups. The results
do not support the use of intensive chemotherapy
as first-line therapy in symptomatic low-grade
NHL. Kimby-E et al., Ann-Oncol. 1994 5 Suppl
2 67-71
145
BEAM chemotherapy followed by autologous stem
cell support in lymphoma patients analysis of
efficacy, toxicity and prognostic factors.
Caballero-MD, et al. Bone-Marrow-Transplant. 20,
451, 1997 AB Patients with NHL (n 112)
received BEAM followed by infusion of bone marrow
(n 55), peripheral blood stem cells (n 79) or
both (n 14) 78 were in CR following ASCT,
including 25 out of 45 patients (56) who were
transplanted with active disease.
146
Only two of the 11 patients transplanted with
resistant disease achieved CR. In conclusion,
the present results demonstrate the efficacy and
low toxicity of the BEAM regimen in high-risk
lymphoma patients with sensitive disease. Other
strategies should be investigated for patients
with refractory lymphoma. Caballero-MD, et al.
Bone-Marrow-Transplant. 20, 451, 1997
147
TI Results of high-dose therapy and
autologous bone marrow/stem cell transplantation
during remission in poor-risk intermediate- and
high-grade lymphoma international index high and
high-intermediate risk group. AU
Nademanee-A et al. AD Department of
Hematology and Bone Marrow Transplantation, City
of Hope National Medical Center, Duarte, CA, USA.
- Bone Marrow Transplant Programme , Stanford
University Medical Center, Stanford, CA SO
Blood. 1997 Nov 15 90(10) 3844-52 AB We
have conducted a pilot study to investigate the
role of high-dose therapy and autologous bone
marrow/stem cell transplantation (ASCT) during
first complete or partial remission in 52
patients with poor-risk aggressive lymphoma..
148
patients number 42 median age 33
(16-56) follicular large cell 6 diffuse
mixed 5 diffuse large cell 21 immunoblastic 10
stage III-IV 37 (88) bulky gt 8 cm 36
(86) IPI High 25 (60) IPI HI 17 (40)
Nademanee, Blood 90, 3844, 1997
149
Thirty-nine were transplanted in first complete
remission and 13 in first partial remission after
conventional therapy. Conditioning regimens
consisted of total body irradiation (TBI)
administered as a single fraction 750 cGy in 3
patients and in fractionated doses for a total of
1,200 cGy in 44 patients, in combination with 60
mg/kg etoposide and 100 mg/kg cyclophosphamide.
Five patients with prior radiotherapy received
450 mg/m2 carmustine instead of TBI. Stem cell
sources were either bone marrow and/or peripheral
blood. No in vitro purging was used.
Nademanee-A et al., Blood. 1997 Nov 15 90(10)
3844-52
150

• FU median 44 months (1-113)
• estimated 3-year OS 84 (95 CI 70 to 92)
• estimated 3-year DFS 82 (95 CI, 68 to 91)
• These results suggest that high-dose therapy and
  ASCT during first remission may improve the
  survival and prognosis of patients with poor-risk
  intermediate- and high-grade lymphoma.
• A prospective randomized study comparing
  high-dose therapy and ASCT with conventional
  chemotherapy in IPI high-risk patients with
  aggressive non-Hodgkin's lymphoma should be
  undertaken.

Nademanee-A et al., Blood. 1997 Nov 15 90(10)
3844-52
151
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152
standard intensive n. 34 33 median
age 49 (19-60) 37 (23-60) centroblastic 18
19 immunoblastic 2 1 T cell 4 3 unclassifi
ed 5 8 Ki-1 3 1 other 2 1 bulky 2
2/34 18/33 stage IV 27/34 25/33 adverse
features 2 23/34 15/33 adverse features
3 11/34 18/33
Pettengel J Clin Oncol 14, 586, 1996
153
standard intensive number 60 61 median
age 49(19-60) 45 (18-60) large cleaved
(G) 37 37 l.c. with LG component 5 6 immunobl
astic 16 7 anaplastic 2 11 stage
II 17 18 stage III-IV 43 43 bulky gt
10cm 26 31 bone marrow 10 15 adverse
features 0-1 16 23 adverse features 2-3 44 38
Cortelazzo Br J Haematol 99, 379, 1997
154
CHOP m-BACOD ProMACE MACOP-B CytaBOM nu
mber 225 223 233 218 age (median) 56
(15-79) 57 (18-81) 54 (17-81) 57 (19-79)
gt65 26 25 27 24 Bulky 40 41 41 40 Mar
row 25 26 27 27 LDH gt250
45 43 42 43 WF group D-E 14 15 15 14
F-G-H 81 82 81 82 j 5 4 4 4
Fisher, NEJM 328, 1002, 1993
155
standard (50) intensive (48) age 35
(17-60) 34 (18-59) group G 88 91 group
H 12 10 T cell 0 0 stage
I-II 32 28 stage III-IV 68 72 Marrow 0
0 Bulky 70 76 IPI L-IL 2 0 IPI
HI-H 74 94
Gianni et al, NEJM 336, 1290, 1997
156
TI Autologous stem cell transplantation for
aggressive non-Hodgkin's lymphomas in first
complete or partial remission a retrospective
analysis of the outcome of 52 patients according
to the age-adjusted International Prognostic
Index. AU Fanin-R Silvestri-F Geromin-A
Infanti-L Sperotto-A Cerno-M Stocchi-R
Savignano-C Rinaldi-C Damiani-D Baccarani-M
AD Department of Medical and Morphological
Research, University Hospital, Udine, Italy. SO
Bone-Marrow-Transplant. 1998 Feb 21(3)
263-71
157
Fifty-two consecutive patients, aged less than 60
years, with intermediate- or high-grade NHL, and
at least one of the following adverse risk
factors bulky disease, B symptoms or Ann Arbor
stage III-IV, and at least a PR after CHT (and
radiotherapy (RT) on residual mediastinal mass
when required), underwent ASCT conditioned with
BAVC. Sixty-five percent (33/52) of the patients
achieved CR after CHT 69 (36/52) after CHT
RT 90 (47/52) after CHT /- RT ASCT. One
death during conditioning and three major toxic
events after ASCT were recorded. Overall survival
(OS) is 98 at 37 months (16-88) disease-free
survival (DFS) is 100 at 27 months (7-82).
Fanin-R. et al., Bone-Marrow-Transplant. 1998,
21, 263
158
Comparing the observed results with those
expected if patients were treated only with CHT,
the sequential treatment including ASCT conferred
an advantage in terms of CR rate of 14, 23 and
54, respectively, in the low-intermediate (LI),
high-intermediate (HI) and high (H)-risk groups,
respectively. The 2-year OS advantage is 10,
21, 31 and 63, respectively, and the 2-year DFS
advantage is 12, 26, 38 and 39, respectively.
Even more striking is the 5-year projected
advantage in the number of patients alive without
disease, even when considering only the low (L)
(P lt 0.0001) and the LI (P lt 0.0001) risk groups.
Fanin-R. et al., Bone-Marrow-Transplant. 1998,
21, 263
159

• For patients in the higher (HI H) risk groups,
  ASCT should be included in the initial plan of
  treatment as consolidation of first CR or PR
• The differences seen in this study suggest a
  formal comparison in a randomized study also for
  patients in the LI risk group.
• Fanin-R. et al., Bone-Marrow-Transplant. 1998,
  21, 263

160
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161
LINFOMI - Trapianto autologo 1
pazienti 51 sesso maschi 30 femmine 21 et
à media 42 mediana 43 range 15-65
ottobre 98
Dipartimento di Oncoematologia - Università di
Modena
162
LINFOMI - Trapianto autologo 2
Tipo istologico (WF) A-B-C 9
(17,6) D-E-F-G 31 (60,7) H-I-J 11
(21,5) Linea B 39 T 8 nd 4
Dipartimento di Oncoematologia - Università di
Modena
ottobre 98
163
LINFOMI - Trapianto autologo 3
stadio II 7 (13.7) III 12
(23,5) IV 32 (62.7) Bulky 33/50
(66) Midollo 19/46 (41,3)
Dipartimento di Oncoematologia - Università di
Modena
ottobre 98
164
Prospective randomized trial by the NHL
Cooperative Study Group 221 patients with
intermediate- high grade NHL (Working Formulation
F, G, H, K) 3 years CR OS PFS MACOP-B 52
52 36 ProMACE-MOPP 49 45 36 Conclusio
n NO significant differences Sertoli MR et al.
J Clin Oncol 12, 1366, 1994
165
MACOP-B /- radiatio therapy fo diffuse olarge
cell lymphoma. Analysis of the stanford results
according to prognostic indices. n 3 year
FFP 47 52 Compared to historical CHOP data
, MACOP-B does not appear to improve outcome for
patients with poor prognostic features Bartlett
NL, et al Cancer 71, 4034, 1993
166
Intermediate- high grade NHL 4 years n CR
RFS ProMECE-CytaBOM 106 62 59 MACOP-B 104
67 69 p 0.11 Silingardi V. et al,
Leuk-Lymphoma 17, 313, 1995
167
LINFOMI - Trapianto autologo 4
Linea prima 45 recidiva 6
Regime BEAM 41 HDS 7 TBI-Cy 1 altro 2
Dipartimento di Oncoematologia - Università di
Modena
ottobre 98
168
Università di Modena - Azienda Policlinico Diparti
mento di Scienze Mediche, Oncologiche e
Radiologiche
5-10-98
Linfomi 51
LINFOMI - Trapianto autologo 5
169
Università di Modena - Azienda Policlinico Diparti
mento di Scienze Mediche, Oncologiche e
Radiologiche
Trapianti 148
5-10-98
170
LINFOMI - Trapianto autologo 6
Stato pre-trapianto Risposta Valutati
44 Valutati 47 RC 27 (61,3) RC 46
(97,8) VGPR 6 (13,6) RP 1 RP 6 (13,6)
Refractory 1 n.v. (HDS) 7 n.v. (F.U.) 5
Dipartimento di Oncoematologia - Università di
Modena
ottobre 98
171
LINFOMI - Trapianto autologo 7
Pazienti 51 FU (dal trapianto) mesi mediana 21
(1-41) vivi 45/51 (88) vivi RC 43
(84) vivi Rec 2 (4) deceduti 6/51
(12) T.R.M. 1 (2) D.R.M. 5 (10) Totale
recidive 7/51 (14)
ottobre 98
Dipartimento di Oncoematologia - Università di
Modena
172
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173
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174
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175
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176

• Diversi studi ormai suggeriscono che
• HD-CHT è globalmente superiore in pazienti con
  malattia chemiosensibile
• la tossicità è accettabile
• Problemi
• conferma da studi prospettici randomizzati
• fattibile ?
• selezione dei pazienti (overtreatment, costi)
• individuare fattori di rischio
• timing e strategia allesordio o come
  consolidamento?
• Purging?
• non è la soluzione per pazienti con malattia
  refrattaria

177
High-Dose Therapy With Autologous Hematopoietic
Rescue for Follicular Low-Grade Non-Hodgkin's
Lymphoma By Philip J. Bierman, Julie M. Vose,
James R. Anderson, Michael R. Bishop, Anne
Kessinger, and James O. Armitage J Clin Oncol
15445-450. Patients and Methods We performed
a retrospective review of 100 patients undergoing
autologous transplantation for follicular
low-grade lymphoma between April 22, 1983 and
December 31, 1993.
178
Results Sixty-seven patients remained alive and
48 were failure-free. The median follow-up
duration of surviving patients was 2.6 years
(range, 1.0 to 11.7). There were eight (8)
deaths within 100 days of transplantation. Six
additional patients died of nonrelapse causes up
to 912 days after transplantation. Overall
survival at 4 years was estimated to be 65
(95 confidence interval CI, 54 to 75) and
failure-free survival was estimated to be 44
(95 CI, 33 to 55). There was no definite
evidence of a plateau in the failure-free
survival curve. J Clin Oncol 15445-450.
179
The only factor significantly associated with
overall survival and failure-free survival was
the number of chemotherapy regimen received
before transplantation. No significant
differences in outcome were observed between
patients with follicular small cleaved-cell
lymphoma and follicular mixed lymphoma, or
between patients who received peripheral-blood
stem-cell transplants and unpurged autologous
bone marrow transplants. Conclusion Prolonged
failure-free survival is possible following
high-dose therapy and autologous hematopoietic
rescue for follicular low-grade lymphoma. It is
unclear whether patients are cured with this
therapy or if survival is prolonged. J Clin
Oncol 15445-450.
180
Donor Leukocyte Infusions in 140 Patients With
Relapsed Malignancy After Allogeneic Bone Marrow
Transplantation By Robert H. Collins, Jr, Ofer
Shpilberg, William R. Drobyski, David L. Porter,
Sergio Giralt, Richard Champlin, Stacey A.
Goodman, Steven N. Wolff, Wendy Hu, Catherine
Verfaillie, Alan List, William Dalton, Nadine
Ognoskie, Angela Chetrit,
Joseph H. Antin, and John Nemunaitis Patients
and Methods We surveyed 25 North American BMT
programs regarding their use of donor leukocyte
infusions (DLI). Reports of 140 patients were
thus available for analysis.
181
Results Complete responses were observed in 60
(95 confidence interval CI, 51.9 to 68.1) of
chronic myelogenous leukemia (CML) patients who
received DLI and did not receive pre-DLI
chemotherapy response rates were higher in
patients with cytogenetic and chronic-phase
relapse (75.7 95 CI, 68.2 to 83.2) than in
patients with accelerated-phase (33.3 95 CI,
19.7 to 46.9) or blastic-phase (16.7 95 CI,
1.9 to 31.9) relapse. The actuarial probability
of remaining in complete remission at 2 years was
89.6. Complete remission rates in
acute myelogenous leukemia (AML) (n 39) and
acute lymphocytic leukemia (ALL) (n 11)
patients who had not received pre-DLI
chemotherapy were 15.4 (95 CI, 9.6 to 21.2)
and 18.2 (95 CI, 6.6 to 29.8),
respectively. Complete remissions were also
observed in two of four assessable myeloma
patients and two of five assessable myelodysplasia
patients. Complications of DLI included acute
graft-versus-host disease (GVHD) (60 95 CI,
51.4 to 68.6), chronic GVHD (60.7 95 CI,
50.3 to 71.1), and pancytopenia (18.6 95 CI,
12.2 to 25.0). Conclusion DLI results in
complete remissions in a high percentage of
patients with relapsed chronic-phase
CML. Complete remissions are observed less
frequently in patients with advanced CML and
acute leukemia. GVHD and pancytopenia occur
commonly GVHD is highly correlated with
response. J Clin Oncol 15433-444.
182
Hyper-CVAD and High-Dose Methotrexate/Cytarabine
Followed by Stem-Cell Transplantation An Active
Regimen for Aggressive Mantle-Cell Lymphoma By
Issa F. Khouri, Jorge Romaguera, Hagop
Kantarjian, J. Lynn Palmer, William C. Pugh,
Martin Korbling, Fredrick Hagemeister, Barry
Samuels, Alma Rodriguez, Sergio Giralt, Anas
Younes, Donna Przepiorka, David Claxton, Fernando
Cabanillas, and
Richard Champlin Purpose Diffuse and nodular
forms of mantle-cell lymphoma (MCL) are
consistently associated with poor prognosis. J
Clin Oncol 163803-3809.
183
In an effort to improve the outcome, we adopted a
treatment plan that consisted of four courses of
fractionated cyclophosphamide (CY) 1,800 mg/m2
administered with doxorubicin (DOX), vincristine
(VCR), and dexamethasone (Hyper-CVAD)
that alternated with high-dose methotrexate (MTX)
and cytarabine (Ara-C). After four courses,
patients were consolidated with high-dose CY,
total-body irradiation, and autologous or
allogeneic blood or marrow stem-cell
transplantation. Patients and Methods
Forty-five patients were enrolled 25 patients
were previously untreated, 43 patients had Ann
Arbor stage IV disease, and 42 patients had
marrow involvement. Forty-one patients had
diffuse histology, two patients had nodular, and
two patients had blastic variants. J Clin Oncol
163803-3809.
184
Results Hyper-CVAD/MTX-Ara-C induced a response
rate of 93.5 (complete response CR, 38
partial response PR, 55.5) after four cycles
of pretransplantation induction chemotherapy. All
patients who went on to undergo transplantation
achieved CRs. For the 25 previously untreated
patients, the overall survival (OS) and
event-free survival (EFS) rates at 3 years were
92 (95 confidence interval CI, 80 to 100) and
72 (95 CI, 45 to 98) compared with 25 (95 CI,
12 to 62 P .005) and 17 (95 CI, 10 to 43 P
.007), respectively, for the previously treated
patients. When compared with a historic control
group who received CHOP-like regimen, untreated
patients in the study had a 3-year EFS rate of
72 versus 28 (P .0001) and a better OS rate
(92 v 56 P .05). J Clin Oncol
163803-3809.
185
Treatment-related death occurred in five
patients all were previously treated and two
received allogeneic transplants. Conclusion
The Hyper-CVAD/MTX-Ara-C program followed by
stem-cell transplantation is a promising new
therapy for previously untreated patients with
MCL. J Clin Oncol 163803-3809.
186
International Prognostic Index
(I.P.I.) Fattore assente presente stadio I-I
I III-IV LDH normali elevate performance
status 0-1 2 o gt Categoria - rischio RC
OS 5 anni basso 0 92 83 int.
basso 1 78 69 int. alto 2 57 46 alto 3
46 32
Shipp et al., NEJM 329, 387-394. 1993
187
NHL - Overall Survival
high intermediate and high risk patients
64
49
p 0.4
Haioun et al, J Clin Oncol 18, 3025, 2000
188
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189
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190
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191
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192
BEAM chemotherapy followed by autologous stem
cell support in lymphoma patients analysis of
efficacy, toxicity and prognostic factors.
Caballero-MD, et al. Bone-Marrow-Transplant. 20,
451, 1997 AB Patients with NHL (n 112)
received BEAM followed by infusion of bone marrow
(n 55), peripheral blood stem cells (n 79) or
both (n 14) 78 were in CR following ASCT,
including 25 out of 45 patients (56) who were
transplanted with active disease.
193
BEAM chemotherapy followed by autologous stem
cell support in lymphoma patients analysis of
efficacy, toxicity and prognostic factors.
Caballero-MD, et al. Bone-Marrow-Transplant. 20,
451, 1997 AB Patients with NHL (n 112)
received BEAM followed by infusion of bone marrow
(n 55), peripheral blood stem cells (n 79) or
both (n 14) 78 were in CR following ASCT,
including 25 out of 45 patients (56) who were
transplanted with active disease.
194
Only two of the 11 patients transplanted with
resistant disease achieved CR. In conclusion,
the present results demonstrate the efficacy and
low toxicity of the BEAM regimen in high-risk
lymphoma patients with sensitive disease. Other
strategies should be investigated for patients
with refractory lymphoma. Caballero-MD, et al.
Bone-Marrow-Transplant. 20, 451, 1997
195
Gianni A.M. et al.
N Engl J Med 336, 1290, 1997
MACOP-B
HDS-CHT
RC
70
96
P0.001
FFP
49
84
Plt0.001
FFR
70
88
P0.055
EFS
49
76
P0.004
OS 7 years
55
81
P0.09
196
Only two of the 11 patients transplanted with
resistant disease achieved CR. In conclusion,
the present results demonstrate the efficacy and
low toxicity of the BEAM regimen in high-risk
lymphoma patients with sensitive disease. Other
strategies should be investigated for patients
with refractory lymphoma. Caballero-MD, et al.
Bone-Marrow-Transplant. 20, 451, 1997
197
6 year OS PFS ProMACE CytaBOM 46 34 MACO
P-B 41 32 m-BACOD 40 36 CHOP 42
33
Fisher, Cancer Chemother Pharmacol 1997, 40suppl
S42
198
6 year OS PFS ProMACE CytaBOM 46 34 MACO
P-B 41 32 m-BACOD 40 36 CHOP 42
33
Fisher, Cancer Chemother Pharmacol 1997, 40suppl
S42
199
Quali approcci sperimentali?
1. aumentare la dose intensity dei farmaci già in
uso nei protocolli standard
2. Terapia sovramassimale e rescue con
progenitori emopoietici autologhi (midollo o
periferiche)
3. Nuovi farmaci (ndr)
oggi monoclonali allogenico
Fisher, Cancer Chemother Pharmacol 1997, 40suppl
S42
200
Quali approcci sperimentali?
1. aumentare la dose intensity dei farmaci già in
uso nei protocolli standard
2. Terapia sovramassimale e rescue con
progenitori emopoietici autologhi (midollo o
periferiche)
3. Nuovi farmaci (ndr)
oggi monoclonali allogenico
Fisher, Cancer Chemother Pharmacol 1997, 40suppl
S42
201

• Se un paziente non vuole partecipare ad uno
  studio clinico, il CHOP rimane il gold standard
• poiché i pazienti guariti dalla chemioterapia
  sono lt50, sono giustificati approcci terapeutici
  sperimentali per migliorare la nostra possibilità
  di curarare la malattia

Fisher, Cancer Chemother Pharmacol 1997, 40suppl
S42
202

• Se un paziente non vuole partecipare ad uno
  studio clinico, il CHOP rimane il gold standard
• poiché i pazienti guariti dalla chemioterapia
  sono lt50, sono giustificati approcci terapeutici
  sperimentali per migliorare la nostra possibilità
  di curarare la malattia

Fisher, Cancer Chemother Pharmacol 1997, 40suppl
S42
203
Philip et al., N Eng l J Med 333, 1540, 1995)
215 patients at relapse
DHAP
BM harvesting
DHAP
responders (109)
N.R. out
DHAP X 4
ABMT
NHL PARMA protocol
204
ABMT vs CHT in relapsed CHT sensitive NHL

• rispetto alla terapia convenzionale il trapianto
  autologo porta ad un aumento della OS e della EFS
• per il futuro dovremmo condurre studi che
  consentano di stabilire se la tossicità può
  essere ridotta dallimpiego di cellule staminali
  periferiche e di fattori di crescita

Philip NEJM 333, 1540, 1995
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