Compare The Outcome Of Patients With Hematological Malignancies Treated With Allogeneic Stem Cell Transplant In Patients Age Over 50 Conditioned With Reduce Intensity Regimens With Those Under 50 Conditioned With Standard Intensity Regimen In a Rural University Hospital – A Single Institution Experience

Abstract

BackgroundMajority of hematological malignancies occurs in older individuals and most can only be cured with high dose chemotherapy followed by stem cell transplantation. Unfortunately these patients who need transplantation the most cannot tolerate chemotherapy well. Development of reduced-intensity transplant regimens has allowed older patients be treated with allogeneic transplantation. AimsTo compare the outcome of allogeneic hematopoietic stem cell transplantation in patients age over 50 conditioned with reduce dose intensity regimens with those under 50 conditioned with standard dose intensity regimen MethodsWe analyzed retrospectively the data in a cohort of 50 consecutive patients with hematological malignancies treated with allogeneic stem cell transplant. We divided the patients into two groups, those under 50 years and those over 50 years. Those under 50 years received standard dose conditioning regimen, while those over 50 years received reduced dose regimen except for one patient. Cyclosporine and standard dose methotrexate was used as GVHD prophylaxis in patients under 50yrs while Cyclosporine and low dose methotrexate was used in patients over 50. Type of hematological malignancies, disease condition at transplant, type of transplant, conditioning regimen, dose of CD34+ stem cell and nucleated cell infused, day to myeloid and platelet engraftment and day 90 mortality is shown in the table. Patients who received unrelated donor transplant received ATG. Five high risk patients received peri-transplant Keratinocyte Growth Factor. All patients received G-CSF beginning day-0.Patients < 50 years oldPatients > 50 years oldNumber of Patients3020Age18 to 46 years (Median 31 yrs)50 to 69 years (Median 57.5 yrs)Indication for transplantAcute Leukemia & MDS (18), Aplastic Anemia (3), Chronic Leukemia (4), Lymphoma (5)Acute Leukemia & MDS (14), Myelofibrosis (1), Chronic Leukemia (1), Lymphoma (4)Type of transplanta) Sibling - 13b) MUD – 13 (43%)c) Cord Blood/Double Cord- 2/2a) Sibling - 13b) MUD – 6 (30%)c) Double Cord blood - 1Disease Status at Transplanta) Remission - 14b) Active – 15 (50%)c) Unknown - 1a) Remission - 5b) Active – 14 (70%)c) Unknown - 1Conditioning RegimenBu/CTX (11), Bu/Flu (9), CTX/TBI (2), ATG/CTX (2) Melphalan Containing Regimen (6).Mel/Flu (9), Bu/Flu (8), CTX/TBI (1), Bu/CTX (I), Mel/Thio (1).Dose of CD34+ hematopoietic stem cell infusedRange 0.12 x106 to 15.83 x 106 cells/kg (median 3.15 x 106 cells/kg).Range 1.51 x106 to 9.08 x 106 cells/kg (median 4.21 x 106 cells/kg).Dose of Nucleated cell infusedRange 0.22 x 108to 41.46 x 108 cells/kg (median 9.37 x 108nucleated cells/kg).Range 5.19 x 108to 18.32 x 108 cells/kg (median 9.08 108nucleated cells/kg).Day of Myeloid EngraftmentRange 10-30 days. Median 14 daysRange 9 to 21 days. Median 14 daysDay of Platelet Engraftment Range (Median day)Range 10 -42 days. (Median 16 days)Range 10-68 days. (Median 18 days)Engraftment Failure2 Patients (both received cord blood)0 PatientsEarly mortality (day 90)9/30 Patients (30%)9/20 Patients (45%) Results43% of patient < 50 years of age underwent match unrelated donor transplant vs. 30% in those over 50. Four underwent cord blood transplant in patient < 50 yrs. old vs. one in those over 50. 50% of patients had active disease in < 50 years group vs. 70% in those over 50. All but two patients (underwent cord blood transplantation <50 years of age) engrafted. Four patients died prior to engraftment in each group. Myeloid engraftment occurred at a median day 14 in each group. Platelet engraftment occurred at median day 16 in patients age under 50 years vs. day 18 in patients over 50. One patient with double cord blood transplant had platelet engraftment on day +68 (age >50). Two patients who received cord blood under 50 years group had engraftment failure. Ninety day mortality was 30% in those under 50 vs. 45% in those over 50. ConclusionsReduced intensity allogeneic stem cell transplantation is feasible and well tolerated in older patients with hematological malignancies with good engraftment however with high early (day 90) mortality. 70% of the patients had active disease at the time of transplant which could account for their high mortality. To prevent early peri-transplant mortality patients with active disease should not go to transplant or should be treated with newer chemotherapy or targeted agents to bring them into remission prior to transplantation Disclosures:No relevant conflicts of interest to declare.