Impact of Clinical Factors on Platelet Engraftments In Contemporary Stem Cell Transplantation.

Conditioning regimens utilized to prepare patients for stem cell transplantation uniformly result in suppression of marrow function, leading to prolonged recovery of neutrophils and platelets. Neutropenia increases the risk of infection while thrombocytopenia and prolonged platelet engraftment time can result in increased risk of bleeding as well as morbidities associated with subsequent transfusions. The variations in duration of cytopenias are affected by multiple factors including regimen intensity and other clinical factors.

In this retrospective study of consecutive patients undergoing stem cell transplantation at the University of Rochester between 2005 and 2009 for radiation—containing regimens, and between 2007 and 2009 for non-radiation containing regimens, we assessed the relationship between platelet engraftment times and source of stem cells, type of graft, and the effect of conditioning regimen intensity. Platelet engraftment was defined per standard CIBMTR definitions – platelet engraftment occurred at the first of 3 days of platelet count >20,000/μ L without platelet transfusions for 7 days, and/or the first day of platelet count >100,000/μ L. Guidelines for transfusion support stipulated a 10,000/μ L threshold for platelets in the absence of bleeding and a hemoglobin of 8.0 g/dL for red cells in the absence of other symptoms. The time to platelet engraftment and the number of platelet transfusions required prior to engraftment were analyzed in those patients with platelet nadir <20,000/μ L. Among 507 adult patients (older than 18), 49 did not have a platelet count nadir, and these patients were excluded from the analyses. Of those, 29 had TBI regimens, 16 of which utilized 200 cGy and 13 had radiation dosage 400–800 cGy. 280 of 458 adult patients who had nadir of platelets received conditioning regimens with chemotherapy alone, and 178 received regimens including total body irradiation (TBI). Disease diagnoses for which transplantation was performed in the 458 cases with platelet nadir included ALL (n=34), AML (n=112), CLL (n=17), CML (n=17), NL/NHL (n=189), MM (n=69), and others (n=20).

The 25^th percentile, median and 75^th percentile (days) for the time to platelet engraftment in days, calculated using the method of cumulative incidence for the non-TBI and TBI containing conditioning regimens, are shown below:

With conditioning regimens containing TBI or with chemotherapy alone (non-TBI), both donor type (auto, allo, or matched unrelated donor) and graft type (marrow, PBSCs, or umbilical cord blood) had significant effects on platelet engraftment time, with the longest engraftment times occurring in cord blood transplants. With both TBI and non-TBI conditioning regimens, donor and graft type significantly affected platelet transfusion numbers (p<.0001). Radiation dose-level of TBI had a significant effect on platelet engraftment (p=0.004) and the number of platelet transfusions required. Of the 458 patients who had nadir of platelet counts, 58.7% of the population was female. Gender did not affect the platelet engraftment time for all patients, but affected the platelet and red blood cell transfusion frequencies in TBI patients. Female TBI patients received significantly more platelet transfusions (p<.0001) up to 100 days and significantly more RBC transfusions up to 30 days (p=.007), after which no significant differences were noted up to 100 days (p=.24).

With non-TBI conditioning regimens, gender did not affect the number of platelet transfusions, but females received significantly more red cell transfusions up to 100 days post-transplant (p=0.003).

These data indicate that times to platelet engraftment in stem cell transplant patients in the era of PBSC and reduced-intensity transplant regimens remains longer than two weeks in cases where conditioning regimens result in platelet nadir. This is associated with considerable utilization of transfusion resources. The increased need of RBC and platelet transfusions in females receiving TBI containing regimens and red cells in non-TBI conditioning cases despite similarity in platelet engraftment times is of interest, and underlying causes remain undetermined.

No relevant conflicts of interest to declare.