Donor Cell Acute Myeloid Leukemia after Transplant for Follicular Lymphoma
Authors: Williams Lacey S. , Lai Catherine E. 
Published: November 2019

Donor cell leukemia is postulated to account for up to 5% of all leukemia "relapses" after hematopoietic stem cell transplant (SCT), though in many cases this is the first leukemia diagnosis for the patient if their transplant was for non-leukemia primary diseases. The rarity of the condition and heterogeneity of disease create challenges in diagnosis and management. In the present case, donor cell leukemia (DCL) developed in a 68-year-old female after allogeneic SCT 18 years earlier for follicular lymphoma. Only one other case of DCL after transplantation for follicular lymphoma has been reported (Boulton-Jones et al., Bone Marrow Transplantation, 2005). Furthermore, this case is atypical in that the presentation occurred many years after transplantation, since very few cases of DCL occur more than 15 years after original transplant.
Case
In 1993, the patient was diagnosed with stage IIIA follicular lymphoma at age 50. She achieved a complete remission with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) for 4 years. She relapsed in 1998 and received treatment with fludarabine and mitoxantrone. In 1999, she enrolled in a toxitumomab clinical trial (NCT00268203) but discontinued therapy secondary to side effects. Due to persistent disease, she proceeded with SCT and received EPOCH-F (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and fludarabine) prior to allogeneic SCT from her brother in 2000 (6/6 HLA match), augmented with TH2 cells. She received graft versus host disease (GVHD) prophylaxis with cyclosporine, however her post transplant course was complicated by engraftment syndrome and gastrointestinal and skin GVHD.
In 2019, she presented to hematology for evaluation of worsening chronic neutropenia and thrombocytopenia persistent for three years, noted during work-up for symptomatic cholelithiasis. Bone marrow biopsy revealed acute myeloid leukemia (AML) with a hypocellular marrow with 30% blasts and myelodysplasia related changes. Her cytogenetics showed 46XY, +1, der(1;7)(q10;p10)/47,sl,+8/46,XY. FISH analyses demonstrated deletion 7q31 D7S486 locus in 156/200 cells (78%). NGS panel showed IDH1 (VAF16%) and U2AF1 (VAF 26%) mutations. Based on cytogenetics and chimerism studies showing 100% donor, the patient was diagnosed with donor-derived AML secondary to allogeneic SCT from her brother. The brother currently has no known hematologic problems.
The patient was treated with CPX-351 (liposomal cytarabine and daunorubicin) and achieved a complete remission, followed by consolidation with CPX-351. Given her complex cytogenetics and poor prognosis, the patient proceeded to non-myeloablative haploidentical peripheral blood SCT from her son, with post-transplant cyclophosphamide. She subsequently had complications of neutropenic fever and C. dificile colitis, with progressive colitis leading to her death on day 22 after SCT.
Discussion
Though cytogenetic and molecular studies along with functional status assist clinicians in treatment decisions for DCL patients, the benefits and risks of treatment remain difficult to balance for this unique subset of leukemia. Of patients that achieve remission for greater than 18 months, many undergo second allogeneic SCT, however a similar number of patients have remissions of at least 18 months treated with chemotherapy alone (Wiseman, Biology of Blood and Bone Marrow Transplantation, 2011). In 15 reported cases that went to SCT, approximately 50% lived longer than 12 months after their DCL diagnosis. Second allogeneic SCT is often favored after initial remission in patients with good performance status due to high risk for relapse. This case illustrates the challenge in management of donor cell leukemia, a rather rare entity with very few cases in the literature developing greater than 15 years after transplant. Limited robust evidence favoring a particular treatment supports the need for further prospective studies.

Disclosures
Lai: Agios: Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Speakers Bureau; Astellas: Speakers Bureau.