Improved Survival in Patients with Refractory Cytopenias (Low Risk Myelodysplastic Syndrome - MDS) Treated with Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplants (allo TCD-HSCTs),

Controversy exists regarding optimal treatment for pts with MDS with low blast percentages. Benefits of early transplant versus transplant-related morbidity and mortality have been debated. With increased time to transplant, MDS pts are more likely to undergo increased numbers of blood transfusions, experience more cytopenias, and are at risk of disease progression. Transplant offers a cure for MDS, and advances in supportive care during and after transplantation have afforded better outcomes and increased numbers of older pts to undergo transplant. Depletion of mature T cells from allogeneic HSCTs decreases the incidence of GvHD and its associated morbidity and mortality. This study therefore evaluated outcomes of pts with refractory cytopenias with less than 5% marrow blasts, who underwent T-cell depleted HSCTs from matched or mismatched, related or unrelated donors at a single center.

Between February 1982 and May 2010, 44 pts with refractory cytopenias(marrow blasts <5%) underwent alloTCD-HSCTs at MSKCC. Thirty pts had de novo MDS, 8 therapy-related, and 6 post aplastic anemia. Median age was 37 yrs (range 9.5–63.5). The MDS subtypes by WHO criteria were: refractory anemia (10), refractory anemia/cytopenia with ringed sideroblasts (2), and refractory cytopenia with multilineage dysplasia (32). Prognosis and risk categories at diagnosis in pts with de novo and post aplastic anemia were determined using 3 scoring systems. Prognosis by IPSS was: low risk (2), intermediate risk-1 (32), intermediate risk-2 (2), unknown (2 – no cytogenetic studies); by WPSS criteria: very low (1), low (12), intermediate (16), high (7), unknown (2); and by MDACC criteria in 34 pts: category-1 (lower risk) (6), category-2 (27), category 3-(1). All pts were severely cytopenic and/or transfusion or cytokine-dependent before alloTCD-HSCT. The median time from diagnosis to transplant was 0.6 years (range 0.11–7.87). Pts were conditioned for transplant with regimens that either included high dose TBI plus chemotherapy (26) or chemotherapy only but including IV busulfan (18). Anti-thymocyte globulin was given for rejection prophylaxis to 40 pts. HSCT donors were: siblings (24) or unrelated donors (20); 12 of the 44 donors were mismatched. Stem cell source was bone marrow (22) or GCSF-primed peripheral blood (22). T cells were removed ex-vivo from the bone marrow grafts with soybean lectin agglutinin and rosetting with sheep red blood cell (sRBC) and from the peripheral blood stem cell grafts by positive selection with a CD34 antibody (Isolex) followed by sRBC rosetting. No posttransplant immunosuppression was given.

Forty-one of the 43 pts evaluable for engraftment recovered ANC >500cells/uL at a median of 11d (range: 9–22). Two pts had primary graft failure, and 3 had secondary graft failure. Four of these pts underwent second transplants. Acute GvHD, grade 1–2, developed in 3 pts. Three additional pts developed grade 3 GvHD, 2 after DLI given for refractory opportunistic infections and 1 after a second unmodified transplant for graft failure. Chronic GvHD occurred in 3 pts, one of whom had received a second unmodified transplant for graft failure. As of May 2011, 16 pts have expired. Causes of death included: GvHD (5, including post DLI), infections (5), graft failure/poor graft function (3), regiment-related toxicity (2), and late death due to lung cancer (1). Twenty-eight pts are alive and doing well with a median survival of 2.8 years (range: 0.5–21.43). The 2-year and 5-year survivals are: 70.1% and 63.3%. Younger recipient age (<50), favorable MDACC score, chemotherapy only preparative regimen, and recent transplants (≥ 2000) indicated a better survival but differences did not reach statistical significance. Survival was not associated with etiology, HLA matching, source of stem cells, IPSS, or WPSS in this series of patients.

Treatment of MDS pts with refractory cytopenias with alloTCD-HSCTs from matched and mismatched related and unrelated donors cures >60% of pts beyond 5 years, with a low incidence of acute and chronic GvHD. These findings support early transplant in the treatment of MDS with refractory cytopenias, especially in younger pts.

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