T-Cell Depletion Is An Alternative Approach for Patients >/= 55 Years Undergoing Allogeneic Stem Cell Transplantation as Curative Therapy for Hematologic Diseases

Abstract 1338

Despite the risk of allogeneic hematopoietic stem cell (HSC) transplantation compared to chemotherapy, it is the only potentially curative therapy for many hematologic diseases. As a consequence, the medical community constantly strives to make this treatment modality available to an expanding array of patients (pts). Although the median age for development of many hematologic malignancies is 50–70 yrs, until the last 10 yrs publications on allogeneic transplantation in adult pts >50yrs and especially those > 65 were limited. The eligibility of such pts for transplant has been tempered by reports of increased toxicity to myeloablative conditioning regimens and higher rates of graft versus host disease (GvHD). The majority of these pts received grafts from matched related donors. The growing population of senior adults in the civilized world and the rising cost of healthcare have focused new attention on these groups. T cell depletion (TCD) of HSC grafts is a modality which has been shown to reduce the incidence and severity of GvHD. It has also made transplantation an option for older pts, who require an unrelated donor, for whom the risk of GvHD is even higher. We retrospectively reviewed a 15 year experience using TCD HSC transplants for pts > 55 years with hematologic malignancies at Memorial Sloan-Kettering Cancer Center (MSKCC). Data collection, which was by medical record and laboratory database review, and analysis were performed with the approval of the Institutional Review Board (IRB) of MSKCC. Protected health information was coded in accordance with requirements of Health Insurance Portability and Accountability Act. From February1995 thru February, 2010,151 pts were identified with only 25 pts transplanted prior to 2000. All patients had provided informed consent for treatment on an IRB approved protocol or a treatment plan. A diagnosis of acute leukemia (AML-29 primary, -48 secondary; ALL-7; ABL-3); CML/MPD (16); MDS (35) or NHL/MM/other (11) was pathologically confirmed at MSKCC prior to transplant. The majority of pts with AML and ALL were in a remission at the time of transplant. Median age was 60.5 yrs (range 55–72). Fifty-five percent were CMV+ pretransplant. Donors were matched (69) and mismatched (5) related, and matched (47) and mismatched (29) unrelated. Mismatched donors were > 8/10 HLA matched. The HCT comorbidity index scoring for the pts was 10% low, 35% intermediate and 55% high. The conditioning regimen used in 90/151 pts was busulfan (8-9.6 mg/kg), melphalan (140mg/m²) and fludarabine (reduced intensity), and 59/151 received a myeloablative TBI-containing regimen. Growth factor mobilization of peripheral blood stem cells (PBSC) provided 81% of the grafts, bone marrow (BM) was the source for 12% and 7% of pts received BM + PBSC. PBSC initially underwent CD34+ selection and BM was treated by soybean agglutination, and both were further depleted by sheep red blood cell rosetting. None of the pts received any posttransplant drug prophylaxis for GvHD. With a median follow up of 12.3 mos. (range 0.4–160.3), Kaplan Meier analysis for the OS and the DFS are 48.6% and 38.3% at two yrs, respectively. The 100d non relapse mortality was 11%. There were 35 relapses, 19 related and 16 unrelated. The incidence of acute (gr 2–4) and chronic GVHD was 15% and 10% (5% extensive), respectively. Deaths were almost equally divided between relapse, infection and GVHD. Notably, for the 27 pts > 65 yrs, with a median followup of 12.9 mos., all of the outcomes were similar to those of the entire group. Acknowledging the limitations of a retrospective review, this study represents one of the largest single center reports for pts > 55 yrs. It demonstrates that TCD HSC transplantation affords a curative therapy with minimal GVHD despite age and lack of a related donor. It provides support for continued investigation of TCD as an alternative approach to transplantation in this older population especially as the technology for TCD has been simplified and supportive care has improved.