Chest Radiology Conference 7202

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Chest Radiology Conference7/2/02

• Kenneth T. Horlander, MD
• Emory University

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X Year Old Male With Fever, Malaise, and Cough

• This admission presented to EUH 6/15/02.
• 54 year old man, Heart Transplant 1/15/02.
• Symptoms including fever, non-productive cough,
  and malaise all started approximately 1 month
  prior to admission and have been getting
  progressively worse.

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• Social 50 pack-year history previous smoker,
  quit 5 years ago
• Physical Exam 97 on 2l n/c,
• A-a gradient 30
• Lung exam revealed prolonged expiratory phase.
• No clubbing, cyanosis, nor edema
• No lymphadenopathy

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Tissue Is The Issue
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• Transthoracic needle biopsy one of the pleural
  based lesions lymphosytes flow cytometry
  showed CD-20 positive Lymphocytes B cells,
  Monoclonal.
• Open biopsy via mediastinoscopy was performed
  architecture seen rubbery white mass with areas
  of necrosis.
• Diagnosis Monomorphic Diffuse Large B Cell
  Lymphoma. EBV positive (LMP-1 antigen).

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Pathology
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Necrosis
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Discussion
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Lymphoproliferative Disorders Following Solid
Organ Transplant

• Most common malignancy complicating organ
  transplant
• 21 of all malignancies (5 in general
  population)
• Non-Hodgkins lymphoma 95 (65 in gen. Pop.)
• Mostly large cell, b-cell, 70 extranodal
  involvement

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Lymphoproliferative Disorders Following Solid
Organ Transplant

• B cell proliferation induced by infection with
  Epstein Barr virus in setting of chronic
  immunosuppression
• Recipient origin PTLD multisystem disease,
  presents at 76 months, 5 of 8 died
• Donor origin PTLD limited to allograft,
  presents at 5 months, regresses after reduction
  of immunosuppression

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Lymphoproliferative Disorders Following Solid
Organ Transplant

• 3 types
• -Benign polyclonal B cell lymphoproliferation
  infectious mononucleosis-type acute illness. 2-8
  weeks after induction or antirejection therapy,
  normal cytogenetics (55 of cases).
• -Polyclonal B cell lymphoproliferation with
  evidence of early malignant transformation, ie
  clonal cytogenetic abnormalities and
  immunoglobulin gene transformation (30).
• Monoclonal B cell proliferation - malignant
  transformation, immunoglobulin gene
  transformation (15) similar to AIDS related
  lymphomas.

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Lymphoproliferative Disorders following Solid
Organ Transplant

• 50 with extranodal masses GI, lung, skin,
  liver, CNS (20-25), allograft,
• If not due to EBV more virulent (mean survival
  1 month vs 37 mo).
• PTLD 2-6 in heart transplant, 1-3 in renal,
  1-2 in liver 1 overall (30-50x higher than
  general population.
• Higher in those that are more immunosuppressed,
  more if on both cyclosporin and azathioprine, or
  with any antithymocyte Ab (OKT3, or
  antilymphocyte serum).
• More often in the first year, greatest in heart
  transplant.
• Heart transplant more likely to see PTLD in heart
  or lungs (18 vs 6.8).

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Lymphoproliferative Disorders Following Solid
Organ Transplant

• If lung transplant EBV seronegative convert
  then 42 get PTLD.
• Excisional tissue biopsy is required for full
  characterization.
• PATH disruption of the architecture, mono or
  oligoclonal populations (cellular or viral
  markers), EBV infection of many cells.
• Avoid steroid use pre-diagnosis (alters the
  histopath and radiologic evaluation).

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Lymphoproliferative Disorders following Solid
Organ Transplant

• Prevention! Reduction and removal of agents for
  graft acceptance.
• gangcyclovir, acyclovir.
• TREATMENT type 1 2) reduction of
  immunosuppression. Type 3) if severly ill stop
  all immunosuppression, prednisone reduced to 7.5
  10mg / day. Less ill limited disease reduce
  cyclosporin and prednisone by 50 and stop
  Azathioprine (or tacrolimus), another 50
  reduction in 2 weeks if needed.

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Lymphoproliferative Disorders following Solid
Organ Transplant

• Antiviral therapy no good efficacy evidence,
  some anecdotel case reports. Lack of thymidine
  kinase expression in EBV cells due to viral
  latency makes viral therapy alone ineffective.
• Surgical resection localized monoclonal disease.
• Chemotherapy maybe useful in the monoclonal
  form. CHOP (cyclophosphamide, doxyrubicin,
  vincristine, prednisone) tried, as well as
  others.
• Radiation therapy for localized disease, and
  those with CNS disease.

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Lymphoproliferative Disorders following Solid
Organ Transplant

• Interferon alpha has antiviral activity.
  Remission has been seen in case reports. Largest
  series 16 patients 8 got total regression, 7
  failed and then got chemo, 1 didnt get full
  course. At end, 1 died of uncontrolled PTLD
• Ongoing trial evaluating a sequential approach
• - Reduce immunosuppression
• - Interferon alpha
• - ProMACE-cytoBOM plus GM-CSF

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Lymphoproliferative Disorders following Solid
Organ Transplant

• Anti-b cell antibodies anti-cd21 and anti-cd24.
  61 remission, 8 relapse
• Anti-cd20 rituximab
• IVIG in combination with other therapies
• Adoptive immunotherapy lymphokine activated
  autologous natural killer cells (can precipitate
  rejection)

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Lymphoproliferative Disorders Following Solid
Organ Transplant

• PROGNOSIS overall survival rates of 25 35.
  T-cell have extremely poor prognosis. Monoclonal
  have 80 mortality.
• Performance status and whether limited or more
  than one site these were 2 factors that
  predicted prognosis in a multivariate analysis.
  If 1 of these median survival 34 months, if 2
  then 1 month.

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Lymphoproliferative Disorders Following Solid
Organ Transplant
References

• Paya, CV et al. ASTS/ASTP EBV-PTLD task force and
  the mayo clinic organized international Concensus
  development meeting. Transplantation
  1999681517.
• Penn, I. Cancers complicating organ transplant.
  NEJM 1990 3231767.
• Nalesnik, MA et al. The diagnosis and treatment
  of posttransplant lymphoproliferative disorders.
  Curr Probl Surg 1988 25367.

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