Cold agglutinin syndrome following allogeneic transplant

1
Cold agglutinin syndrome following allogeneic
transplant

• Joshua Field
• January 13, 2006

2
Case

• 57 year-old man with a history of chronic
  lymphocytic leukemia (CLL).
• Diagnosed in 1993.
• Lymphocytosis and adenopathy.
• Treated with ProMACE-CytaBOM Procarbazine,
  mechlorethamine, adriamycin, cyclophosphamide,
  etoposide, cytarabine, leuvorin, methotrexate.
• Achieved a remission.

3
Case

• Relapsed 1997.
• Thereafter
• Chlorambucil
• CVP
• Fludarabine
• Rituximab
• Cyclophosphamide, fludarabine, rituximab
• Referred for an allogeneic transplant.
• Workup allogeneic transplant
• ZAP70
• cytogenetics 48 XY, trisomy 12, 19 in 5
  metaphases, deletion 7 in 1 metaphase.

4
Case

• 8/19/05 Day 0 Fludarabine, busulfan,
  thymoglobulin 6/6 matched sibling transplant.
• Reduced conditioning regimen
• Previous therapy
• Graft versus tumor effect
• OPos into OPos
• Course complicated by fevers with thymoglobulin.
• Discharged on 8/30/05 on FK-506.

5
Case

• 9/4/05 Day 17 presented with malaise and
  fevers.
• 2-3 day history of fatigue.
• Poor PO intake.
• Low-grade fevers 100.8.
• Admitted to 5900 and bloodwork sent.

6
Case
MCV 100.6
9.8
100
136
35
38
76
0.8
5.0
25
T. bilirubin 1.8
PT 14.3
AST 315
INR 1.06
ALT 255
PTT 31
LDH 1981
7
Washed, Warmed
8
Case
9
(No Transcript)
10
Hospital Admission
11
Case

• Additional labs
• Reticulocyte 2.5
• Haptoglobin lt7

12
Peripheral smear
13
Autologous Cells
14
(No Transcript)
15
(No Transcript)
16
Cold agglutinin syndrome

• Less common than WAIMA.
• Average age 66.
• Symptoms and signs
• Key is the thermal amplitude.
• Acrocyanosis
• Hemoglobinuria
• Anemia pallor, fatigue, dyspnea, weakness.
• Splenomegaly.

17
Cold agglutinin syndrome

• Idiopathic
• Secondary
• Non-malignant
• Mycoplasma
• EBV
• Malignant lymphoproliferative disorders.
• Post-transplant?

18
Cold agglutinin syndrome

• Laboratory findings
• Autoagglutination intense at 4C, reversible at
  37C.
• DAT IgG-C3 (100).
• Smear agglutinated red cells, less spherocytes,
  polychromasia.
• Hemolysis
• IgM target I, i, Pr
• Course typically chronic, mild to moderate
  anemia (Hgb 9-12 g/dL).

19
(No Transcript)
20
Treatment

• Avoid cold
• Steroids not terribly effective
• Immunosuppression
• Chlorambucil 2-4 mg/day
• Rituximab
• Fludarabine
• Plasma exchange
• Cumbersome warm room, blood, inpatient.
• Effects short-term
• Splenectomy ineffective
• CLL
• 5
• Treat the CLL.

21
Post-transplant hemolysis

• ABO
• Minor incompatibility O?A
• Passenger lymphocyte syndrome day 10
• Major incompatibility A?O
• Microangiopathy
• TTP
• DIC
• Autoimmune hemolysis
• CAIHA
• WAIHA

22
Minor incompatibility

• Manipulation of product plasma reduce lt 300 cc
  (less if titers gt 256)
• Check isohemagglutinin titers of donor.
• Antibodies produced by lymphocytes in infused
  product
• DAT positive 4-18 days post transplant.
• Typically
• IgG mediated
• Direct to ABO
• Anti-A or B titers pre-transplant do not predict
  hemolysis (Hows, et al. Blood, 1986).
• Treatment
• Supportive
• Severe hemolysis consider plasma or red cell
  exchange.

23
Major incompatibility

• Manipulation of product
• Red cell reduced lt 10 cc
• Check isohemagglutinin titers in recipient.
• Stussi, et al. Bone Marrow Transplantation, 2002.
• Delayed red cell engraftment (P0.0001)
• Pure red cell aplasia (6).
• No overall effect on survival, engraftment of
  other cell lines or GVHD.
• Worel, et al. Transplantation, 2000.
• Delayed red cell engraftment (32 days vs. 20
  days)
• Pure red cell aplasia (3)
• Treatment is plasma exchange.

24
Post-transplant autoimmune hemolysis

• Incidence following transplant 3 (Abou-Elella,
  et al. Transfusion, 1995).
• From where does the antibody arise? (Chen, et al.
  Bone Marrow Transplantation, 1997)
• Donor antibodies
• 2 groups of patients cold antibody (2-6 months
  post-transplant), warm antibody (12-18 months
  post-transplant)
• Correlates to the production of IgM and IgG by
  engrafted B cells.
• T cell depletion

25
Case

• Diagnosed with cold agglutinin syndrome.
• Previously initiated on steroids due to presumed
  GVHD.
• Transfusion medicine consulted for consideration
  of plasma exchange.
• Performed 8 procedures while as an inpatient,
  approximately qod.
• 1.5 L all albumin exchange.
• Room heated to 90F.
• Received warmed PRBCs.

26
Case

• Treated with anti-CD52 monoclonal antibody
  campath.
• 5 doses daily SQ.
• Treated with rituximab anti-CD20 monoclonal
  antibody.
• Day 30 STR 87 donor 13 patient
• Day 100 STR gt95 donor

27
PEX
Day 0
Campath
Rituxan
28
(No Transcript)