Acute leukemia of donor origin arising after stem cell transplantation for acute promyelocytic leukemia.

We report a patient with PML/RARalpha-positive acute promyelocytic leukemia (APL) who developed PML/RARalpha-negative acute myeloid leukemia 37 months after allogeneic bone marrow (BMT) transplant for molecular relapse. Features of myelodysplasia were noted 11 months earlier, chimerism testing by analysis of short tandem repeats was consistent with development of myelodysplasia and acute leukemia within cells of donor origin. To our knowledge, this is the first report of donor cell leukemia following BMT for APL. We hypothesize that replicative stress may lead to the development of some cases of donor cell acute leukemia.

Transplantation-associated thrombotic microangiopathy is associated with transplantation from unrelated donors, acute graft-versus-host disease and venoocclusive disease of the liver.

Transplantation-associated thrombotic microangiopathy (TA-TMA) has been associated with significantly reduced survival following allogeneic bone marrow transplantation. In this study we describe the course and response to plasma exchange therapy of TA-TMA as well as risk factors for its' development. Twenty-five patients who underwent plasma exchange therapy were matched to fifty control patients selected for transplant indication and stage of disease at the time of transplant. Transplant indications were acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, aplastic anemia, myelodysplastic syndrome and multiple myeloma. Groups were well balanced with respect to disease status, age at time of transplant and use of radiation-based conditioning. TA-TMA was diagnosed a median of 27 days after transplantation and neurological abnormalities were present in ten cases. Patients received a median of 10 (range 2-43) plasma exchange treatments. Hematological responses were recorded in eight cases. Risk factors for the development of TA-TMA included transplantation from unrelated donors (p = 0.002), hepatic venoocclusive disease (VOD) (p = 0.034), grade 2-4 acute graft-versus-host disease (GVHD) (p = 0.042) and bacteremia with diphtheroid organisms (p = 0.009). Only hepatic VOD (p = 0.0026) and grade 2-4 acute GVHD (p = 0.0436) remained significant risk factors for later development of TA-TMA in a multivariate logistic regression model. The median survival of patients with TA-TMA was 66 (range 32-733) days while that of unaffected patients was 742 (range 15-2392) days after transplantation. Only one patient with TA-TMA remains alive 733 days after transplantation.

Influence of one human leukocyte antigen mismatch on outcome of allogeneic bone marrow transplantation from related donors.

This study compares the clinical outcomes of 60 consecutive patients who received an allogeneic blood or marrow stem cell transplant (BMT) from one Human Leukocyte Antigen (HLA) mismatched related donors with those of 120 matched patients who had HLA identical sibling donors. The control patients were matched for diagnosis, disease status, conditioning regimen, and age at BMT. All patients received standard CYA and MTX for GVHD prophylaxis. The probability of overall survival (OS) at 5 years was 35% in the study group compared to 56% in the control group. The relapse rates and acute GVHD rates did not differ between the two groups. Graft failure was a significant problem in the study group compared to the control group (13 vs. 0%, p < 0.0001). All cases of graft failure occurred in patients with a mismatch in the host-versus-graft direction. BMT-related deaths were also increased in the study group. Forty percent of deaths were caused by infection in the study group vs. 19% in the control group (p < 0.01). In conclusion, the OS of patients receiving marrow/stem cells from one antigen mismatched related donors was inferior to that of controls with HLA-identical related donors. There was an increase in mortality related to infections occurring in the setting of an increased frequency of graft failure in these patients.

Complete remission of tumour with interleukin 2 therapy in a patient with non-Hodgkin's lymphoma post allogeneic bone marrow transplant associated with polyclonal T-cell bone marrow lymphocytosis.

A patient with low-grade non-Hodgkin's lymphoma (NHL) who relapsed shortly after an allogeneic bone marrow transplant (BMT) is reported. The patient was treated with interleukin 2 (IL-2), which resulted in a flare-up of graft-versus-host disease followed by disease control, with disappearance of peripheral lymphadenopathy. Sequential bone marrow testing showed the disappearance of bone marrow involvement with disease but occurrence of T-cell aggregates post IL-2 that were identified as polyclonal by molecular methods. The patient remains in complete remission 37 months following allogeneic BMT.