Emily Andersen, CNP AMG Hematology and Bone Marrow Transplant Objectives PTLD Incidence Risk factors Presentation Treatment/Chemotherapy Prognosis Anemia and Pancytopenia Risk.
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Emily Andersen, CNP AMG Hematology and Bone Marrow Transplant Objectives PTLD Incidence Risk factors Presentation Treatment/Chemotherapy Prognosis Anemia and Pancytopenia Risk factors/types Presentation Treatment Incidence Who? Patients exposed to systemic immunosuppression EBV naïve at highest risk More common in heart and lung transplants (10%) Second most common malignancy in adult transplant recipients; most common malignancy in pediatric transplant recipients What? Expansion of recipient origin B cells latently infected with EBV May compromise graft function Parker et al. (2010) Incidence Where? HEENT most common, although it can occur anywhere May even present in transplanted organ When? First year most common, but onset and duration are variable amongst patients Why? “Impairment of EBV-specific, cytotoxic T-cell function by systemic immunosuppression” Largely EBV-driven – crosses from infection to Parker et al. (2010) malignancy Smith (2010) 5-yr incidence of non-Hodgkin lymphoma Relative risk of NHL: Heart-lung 239.5 Lung 58.6 Heart 27.6 Liver 29.9 Pancreas 34.9 DD kidney Tx 12.6 Risk Factors Transplant type Small bowel > Lung > Heart/lung > Heart > Liver > Kidney Immunosuppressive regimen Cyclosporine vs Tacrolimus Intensity of immunosuppression Age Under 10 and over 60 years of age Parker et al. (2010) Approximate Frequency of PTLD in patients by organ transplanted and age Organ Adults (%) Pediatric (%) Kidney 1.0 – 2.3 1.2 – 10.1 Liver 1.0 – 2.8 4.0 – 15.0 Heart 1.0 – 6.3 6.4 – 19.5 Heart/Lung 2.4 – 5.8 6.4 – 19.5 Lung 4.2 – 10.0 6.4 – 19.5 Small bowel 20 30 Parker et al. (2010) Presentation Not a “typical” presentation Usually no lymphadenopathy May or may not have constitutional symptoms Presenting symptoms linked to site of involvement HEENT GI tract Bone marrow Parker et al. (2010) Diagnosis Biopsy Surgical excisional biopsy is preferred over core needle biopsy Histopathological evaluation Imaging Ultrasound MRI CT scan PET scan Parker et al. (2010) Treatment/Chemotherapy Dependent on many factors Age Co-morbidities Aggressiveness of PTLD Treatment Reduction in immunosuppression Antiviral therapy Rituxan Rituxan + combination chemotherapy (R-CHOP) Elstrom et al. (2006) Parker et al. (2010) Prognosis Caillard et al. (2006) Anemia and Pancytopenia Variety of causes/types Passenger lymphocyte syndrome Drug-induced cytopenias Viral infections Smith (2010) Passenger Lymphocyte Syndrome Caused by ABO-mismatch Abrupt onset at 1-3 weeks Decreased Hgb, haptoglobin Increased LDH, bilirubin Positive direct antiglobulin test Treatment Supportive care Self-limiting after ~3 months Smith (2010) Drug-induced Cytopenias Can be caused by numerous drugs Drug not specific to SOT Bactrim Drugs specific to SOT Antivirals Immunosuppressants Smith (2010) Viral infections Opportunistic infections Parvovirus B19 CMV Human herpes virus 6 Smith (2010) Conclusions PTLD Severity, prognosis, and treatment widely vary Biopsy, imaging, and Hematology/Oncology consult Rituxan or R-CHOP shown to be effective but have higher risk of side effects Anemia and cytopenias Many differentials to consider Must identify source to treat appropriately Case Study O.L. – 7o y/o WM 3 months s/p kidney transplant from deceased donor Radiation nephritis (history of lymphoma 1982) Transplant complicated by steroid induced psychosis Maintained on low-dose Myfortic and Tacrolimus Baseline Crt 1.3-1.5 Neutropenia – Bactrim and Valcyte held Presents with tremor, increasing crt, thrombocytopenia, unintentional weight loss, GI complaints Case Study What further tests would you order? What things about his presentation are concerning? Case Study Labs CBC WBC 4.9 Hgb 7.9 Hct 24.6 Plt 37 BMP Na+ 130 K+ 3.8 BUN 28 Crt 2.7 CMV Positive for infection Case Study Imaging CT chest/abd/pelvis Stable mild adenopathy to the mesentary Mild acute diverticulitis New right renal transplant No significant recurrent adenopathy below the diaphragm. No significant thoracic adenopathy. Enlarge mediastinal lymph node? Causing extrinsic compression of esophagus Bone marrow biopsy No evidence of lymphoma Case Study Patient underwent esophageal ultrasound for further assessment of lymph nodes Abnormal mediastinal lymph node discovered FN biopsy performed CD 10 positive B-cell lymphoma Kidney biopsy performed to r/o rejection Atypical lymphocytic proliferation Case Study What is your differential diagnosis? What is the next step? What things do you need to consider in deciding on a treatment plan? Case Study Patient treated with Rituxan 375mg/m2 weekly x 4 weeks CHOP not given d/t patient’s health status, co- morbidities Steroids with Rituxan lowered d/t patient’s history of steroid-induced psychosis IV Ganciclovir for CMV infection Immunosuppression decreased to low dose Tacrolimus only (goal level 3-5) Case Study Patient tolerated Rituxan infusions well with the exception of some transient worsening confusion d/t steroid pre-meds PET scan performed Some response and reduction to lymph nodes with Rituxan Some residual hypermetabolism in mediastinal lymph nodes Patient given two options Four additional cycles of Rituxan Watchful waiting with repeat PET scan in 3-4 months Case Study Repeat PET scan 3 months later New bulky adenopathy in the retroperitoneum Tacrolimus discontinued and patient started on everolimus Patient had received one dose of Rituxan upon his return to our clinic Patient still not candidate for CHOP therapy Decided to proceed with Rituxan/Treanda – received one cycle and had confusion d/t steroids Patient/family decided to hold off on more treatment Case Study Repeat PET scan 3 months later Complete resolution of lymphoma in the chest Marked improvement in the lymphadenopathy in the retroperitoneum Continued with watchful waiting Repeat PET scan 3 months later Aggressive recurrence with large mass in the chest and worsening disease in the retroperitoneum Patient decided against further treatment and opted for comfort cares/hospice References Elstrom, R.L., Andreadis, C., Aqui, N.A., Ahya, V.N., Bloom, R.D., Brozena, S.C., . . . Tsai, D.E. (2006). Treatment of PTLD with Rituximab or Chemotherapy. American Journal of Transplantation, 6, 569-576. Parker, A., Bowles, K., Bradley, J.A., Emery, V., Featherstone, C., Gupte, G., . . . Newstead, C. (2010). Diagnosis of post-transplant lymphoproliferative disorder in solid organ transplant recipients – BCHS and BTS Guidelines. British Journal of Hematology, 149, 675-692. Smith, E. (2010). Hematologic disorders after solid organ transplant. American Society of Hematology, 281-286.