Optimizing recovery from aplasia after high-dose therapy and hematopoietic stem cell transplantation

Abstract

Objective. Discussion of the roles of hematopoietic growth factors and the role of stem cells in shortening aplasia after transplant. In addition, the role of the treatment regimen in determining the length of aplasia. Data Sources. A series of original research stud ies from H. Lee Moffitt Cancer center which was published from 1993 to the present. In addition, selected references were reviewed and quoted to support selective arguments. Study Selection. Since 1989 data from four allo cated, parallel, high-dose phase I/II trials conducted at H. Lee Moffitt Cancer Center, Tampa, Fla and include the following treatment regimens: (1) ifosfamide, carbo platin, and etoposide (ICE); (2) mitoxantrone and thio tepa (MITT); (3) busulfan and cyclophosphamide (BUCY2); and (4) Taxol, Novantrone, thiotepa (TNT). The results of hematopoietic recovery from consecutive patients allocated on these trials will be discussed. Data Extraction. Granulocyte engraftment was defined as having occurred when an absolute granu locyte count of 500/μL has been surpassed on 3 or more consecutive days. The period of aplasia was defined as the number of days from the day of stem cell infusion to the day of engraftment. The period of granulocyte engraftment and aplasia was examined comparatively as a function of the source of stem cells given to the patient at their initial reinfusion. Time to engraftment was evaluated by Kaplan-Meier Product Limit Method and probability curves were compared by logrank analysis. Data Synthesis. The duration of aplasia after high-dose therapy and stem cell transplantation deter mines the risk of opportunistic infection and the cost of the transplant. Prospective, randomized, controlled trials for both sargramostim and filgrastim have clearly demonstrated a significantly shorter period of aplasia produced by high-dose therapy by several days. From sequential comparison trials, it appears that filgrastim may be superior to sargramostim in shortening aplasia after bone marrow stem cell transplantation following high-dose therapy. Erythropoietin, while not shorten ing the period of aplasia, has been demonstrated to reduce erythrocyte transfusion requirements; whereas the question about cost-effectiveness remains to be unanswered. In comparing granulocyte recovery of bone marrow stem cell transplants with peripheral blood stem cell transplants, both perform similarly, especially, if collected under identical stimulatory conditions. Both the mobilizing regimen and the treatment regimen, but not the anatomic compart ment, are significant factors which determine the speed of engraftment after high-dose therapy and hematopoietic stem cells are transplanted. Conclusions. The purpose of high-dose therapy is to improve the cure rate for selected malignancies. Shortening aplasia can reduce the death rate from infections but only has a marginal impact on the cure rate as the death rate is relatively low. It behooves us, then, to develop the best treatment and with that regimen determine how best to shorten the period of aplasia.