Abstract
Majority 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.
To 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
We 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 old . | Patients > 50 years old . |
---|---|---|
Number of Patients | 30 | 20 |
Age | 18 to 46 years (Median 31 yrs) | 50 to 69 years (Median 57.5 yrs) |
Indication for transplant | Acute Leukemia & MDS (18), Aplastic Anemia (3), Chronic Leukemia (4), Lymphoma (5) | Acute Leukemia & MDS (14), Myelofibrosis (1), Chronic Leukemia (1), Lymphoma (4) |
Type of transplant | a) Sibling - 13 b) MUD – 13 (43%) c) Cord Blood/Double Cord- 2/2 | a) Sibling - 13 b) MUD – 6 (30%) c) Double Cord blood - 1 |
Disease Status at Transplant | a) Remission - 14 b) Active – 15 (50%) c) Unknown - 1 | a) Remission - 5 b) Active – 14 (70%) c) Unknown - 1 |
Conditioning Regimen | Bu/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 infused | Range 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 infused | Range 0.22 x 108 to 41.46 x 108 cells/kg (median 9.37 x 108 nucleated cells/kg). | Range 5.19 x 108 to 18.32 x 108 cells/kg (median 9.08 108 nucleated cells/kg). |
Day of Myeloid Engraftment | Range 10-30 days. Median 14 days | Range 9 to 21 days. Median 14 days |
Day of Platelet Engraftment Range (Median day) | Range 10 -42 days. (Median 16 days) | Range 10-68 days. (Median 18 days) |
Engraftment Failure | 2 Patients (both received cord blood) | 0 Patients |
Early mortality (day 90) | 9/30 Patients (30%) | 9/20 Patients (45%) |
. | Patients < 50 years old . | Patients > 50 years old . |
---|---|---|
Number of Patients | 30 | 20 |
Age | 18 to 46 years (Median 31 yrs) | 50 to 69 years (Median 57.5 yrs) |
Indication for transplant | Acute Leukemia & MDS (18), Aplastic Anemia (3), Chronic Leukemia (4), Lymphoma (5) | Acute Leukemia & MDS (14), Myelofibrosis (1), Chronic Leukemia (1), Lymphoma (4) |
Type of transplant | a) Sibling - 13 b) MUD – 13 (43%) c) Cord Blood/Double Cord- 2/2 | a) Sibling - 13 b) MUD – 6 (30%) c) Double Cord blood - 1 |
Disease Status at Transplant | a) Remission - 14 b) Active – 15 (50%) c) Unknown - 1 | a) Remission - 5 b) Active – 14 (70%) c) Unknown - 1 |
Conditioning Regimen | Bu/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 infused | Range 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 infused | Range 0.22 x 108 to 41.46 x 108 cells/kg (median 9.37 x 108 nucleated cells/kg). | Range 5.19 x 108 to 18.32 x 108 cells/kg (median 9.08 108 nucleated cells/kg). |
Day of Myeloid Engraftment | Range 10-30 days. Median 14 days | Range 9 to 21 days. Median 14 days |
Day of Platelet Engraftment Range (Median day) | Range 10 -42 days. (Median 16 days) | Range 10-68 days. (Median 18 days) |
Engraftment Failure | 2 Patients (both received cord blood) | 0 Patients |
Early mortality (day 90) | 9/30 Patients (30%) | 9/20 Patients (45%) |
43% 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.
Reduced 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
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
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