Bone marrow toxicity
Marrow damage and hematopoietic recovery following allogeneic bone marrow transplantation for acute leukemias: Effect of radiation dose and conditioning regimen

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Abstract

Background and purpose

Total body irradiation (TBI) is a common component of hematopoietic cell transplantation (HCT) conditioning regimens. Preclinical studies suggest prolonged bone marrow (BM) injury after TBI could contribute to impaired engraftment and poor hematopoietic function.

Materials and methods

We studied the longitudinal changes in the marrow environment in patients receiving allogeneic HCT with myeloablative (MA, n = 42) and reduced intensity (RIC, n = 56) doses of TBI from 2003–2013, including BM cellularity, histologic features of injury and repair, hematologic and immunologic recovery.

Results

Following MA conditioning, a 30% decrease in the marrow cellularity persisted at 1 year post-transplant (p = 0.03). RIC HCT marrow cellularity transiently decreased but returned to baseline by 6 months even though the RIC group received mostly umbilical cord blood (UCB) grafts (82%, vs. 17% in the MA cohort, p < 0.01). There was no evidence of persistent marrow vascular damage or inflammation. Recipients of more intensive conditioning did not show more persistent cytopenias with the exception of a tendency for minimal thrombocytopenia. Immune recovery was similar between MA and RIC.

Conclusions

These findings suggest that TBI associated with MA conditioning leads to prolonged reductions in marrow cellularity, but does not show additional histological evidence of long-term injury, which is further supported by similar peripheral counts and immunologic recovery.

Section snippets

Patients

Medical records from 98 patients (47 male, 51 female) receiving allogeneic HCT using either TBI-containing MA or RIC regimens at the University of Minnesota between January 2003 and June 2013 were reviewed. Patients were limited to age 45–55 at HCT to avoid confounding age-related differences in marrow cellularity [22], [23].

Preparative regimens

MA conditioning included cyclophosphamide 60 mg/kg on day-6 and -5 pre-HCT followed by 1320 cGy TBI delivered in 8 twice-daily fractions. Those receiving umbilical cord blood

Results

Table 1 describes the demographic and clinical characteristics of the patients in each cohort. The MA and RIC cohorts were similar with respect to diagnosis, disease risk, prior autologous transplants, performance status and CMV serostatus. There was a slight male predominance in the MA cohort (60% versus 40% in the RIC cohort; p = 0.05). The majority (81%) of patients undergoing MA conditioning received hematopoietic stem cell grafts from matched sibling donors while most of the others (17%)

Discussion

In this study, we analyzed the longitudinal impact of MA and RIC regimens on the BM environment and functional reconstitution post-HCT. Due to the fact that there was considerable variation in the conditioning regimen and graft source for the RIC and MA patients, we did not seek to directly compare the individual marrow cellularity measurements and peripheral blood counts at specified time points. Rather, we examined the changes over time compared with the pre-transplant baseline for each

Conflict of interest

The authors declare no conflict of interest.

Acknowledgement

This work was supported by the National Institute of Health grants (1R01CA154491).

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