It is hypothesized that engraftment when administering cyclophosphamide post the stem cell infusion will increase, the incidence of graft versus host disease (GVHD) and day 100 mortality will decrease, and the use of cyclophosphamide post stem cell infusion with alternative donors will be as safe and as effective as traditional matched transplants.
The primary rationale for the development of this research study is to find out if the use of cyclophosphamide after a "blood" stem cell transplant is an effective treatment for patients with blood cancers who require transplant for long-term survival but are without an available matched-sibling donor. Historically, survival rates for patients undergoing partially matched related or unrelated donor transplants (henceforth to be called alternative donor transplants) have been much lower than those observed after matched sibling stem cell transplants. Survival post alternative donor stem cell transplant has also been affected by the requirement to remove or reduce the numbers of donor T cells resulting in higher rates of infection, graft rejection, and relapse. One significant limitation to conventional donor transplants with HLA matched siblings has been that over 50% of patients do not have HLA matched siblings so that increasing the safety of alternative donor transplants could have a significant influence on the number of patients who could safely receive transplants. Because of the historically low overall survival (OS) after alternative donor transplants, it has become a procedure of "last resort" in many centers unwilling to consider it unless all other options are exhausted. There fore several centers including ours have sought to overcome problems using various strategies. The strategy the investigators have proposed for this study (which has been used similarly by other centers) has been to administer cyclophosphamide post the stem cell infusion (traditionally it is given before the stem cell infusion) thereby hopefully destroying the activated T-cells causing graft-versus host disease (GVHD) and allow T cell tolerization and engraftment; but, not the inactivated T cells thereby hopefully preserving the anti-tumor effects of the donor immune system. Thus, the major aim of this study will be to measure the engraftment with this regimen and secondarily to measure incidence of GVHD and day 100 mortality. The goal is to see if in the first 3 months the use of cyclophosphamide post stem cell infusion with alternative donors is as safe and as effective as traditional matched transplants.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
78
Myeloablative HSCT Arm: Total body irradiation (TBI) is given in 8 fractions over 4 days (total dose of 12 Gy) Reduced Intensity HSCT Arm: TBI is given in one fraction (total dose of 2 Gy)
Cyclophosphamide is administered on the third day after the hematopoietic stem cell transplantation (HSCT) to help reduce graft-versus-host disease (GVHD). It is given at a dose of 60 mg/kg/d for 2 days on days +3 and +4.
Started the fifth day after the transplant to help prevent graft-versus-host disease (GVHD).
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Successful Engraftment Using Cyclophosphamide Post-Transplant
Successful Hematopoietic engraftment will be assessed by determining the incidence of participants who achieve both of the following criteria within the 100 days post-transplant: ANC \>/= 0.5x10e9/L for at least 3 days. Platelet engraftment \>20,000 with no transfusions X 7 days. The incidence will be calculated as the number of participants who meet both engraftment criteria. Results will be presented as a proportion/percentage/probability not as an incidence rate.
Time frame: Through 100 days post-transplant
Cumulative Incidence of Grade III-IV GVHD
The cumulative incidence of Grade III-IV graft-versus-host disease (GVHD) within 100 days post-transplant will be estimated; goal is less than 10%. The cumulative incidence represents the probability that a participant experiences Grade III-IV GVHD by day 100. Results will be reported as proportion/percentage/probability.
Time frame: Through 100 days post-transplant
Incidence of GVHD Unresponsive to Corticosteroids and Photopheresis
This outcome will estimate the cumulative incidence (probability) of graft-versus-host disease (GVHD) that is considered unresponsive to corticosteroids and photopheresis within 100 days after treatment; goal is less than 15%. The cumulative incidence will be calculated as the number of participants meeting these criteria. Results will be reported as a proportion/percentage.
Time frame: Through 100 days post-treatment
Transplant-Related Mortality
The cumulative incidence of transplant related mortality (TRM) by day 100 post-transplant will be estimated. Assess day 100 transplant-related mortality; goal is less than 15%. TRM is defined as death that results from medical treatment rather than from the underlying disease itself. The cumulative incidence reflects the probability of TRM by day 100. The result will be reported as a proportion/percentage/probability, not an incidence rate.
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Started the fifth day after the transplant to help prevent graft-versus-host disease (GVHD).
Started the fifth day before the transplant. Given for four days at 30 mg/m2/d.
Started the fourth day before the transplant. Given for two days at 3.2 mg/kg.
Allogeneic marrow transplantation given after the last dose of total body irradiation (TBI)
Time frame: 100 days post-transplant