High-dose cyclophosphamide may reduce severe GVHD after HSCT

Issue: March 25, 2016

Treatment with high-dose cyclophosphamide appeared associated with lower rates of severe graft-versus-host disease, improved transplant-related mortality, and decreased admissions and inpatient hospital stays among patients undergoing hematopoietic stem cell transplantation for hematologic malignancies, according to data presented at the BMT Tandem Meetings.

However, patients treated with cyclophosphamide had lower absolute neutrophil counts and platelet recovery than those treated with tacrolimus and methotrexate, and further study is required before high-dose cyclophosphamide becomes a standard of care, according to the researchers.

The development of graft-versus-host disease (GVHD) is a significant concern for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for blood cancers, according to study background. However, recent studies have suggested high-dose cyclophosphamide as a potential candidate for the prevention of acute GVHD.

Thus, Nasheed Mohammad Hossain, MD, hematologist at Fox Chase Cancer Center, and colleagues sought to compare outcomes based on treatment options for patients undergoing allogeneic HSCT at their institution.

Between 2010 and 2014, Hossain and colleagues identified 105 patients who received an allogeneic HSCT at Fox Chase. Seventy patients received treatment with tacrolimus and methotrexate; the other 35 patients received high-dose cyclophosphamide.

The researchers performed tests to determine rates of severe (grade 3 or worse) acute GVHD, treatment-related mortality, absolute neutrophil counts, platelet recovery, inpatient days and number of readmissions within the first 100 days and 6 months after treatment.

Twelve patients in the high-dose cyclophosphamide group underwent haploidentical transplantation, 17 underwent transplantation from a matched-unrelated donor and six patients underwent matched-related donor transplants.

In the tacrolimus/methotrexate group, 47 patients received matched-unrelated donor transplants and 23 patients received matched-related donor transplants.

Because haploidentical transplantation only occurred among patients in the high-dose cyclophosphamide group, this cohort was considered to have more high-risk patients.

Overall, 20% of patients treated with cyclophosphamide developed severe GVHD, compared with 26% of patients treated with tacrolimus and methotrexate.

Patients treated with tacrolimus and methotrexate achieved longer OS (median, 773 days vs. 354 days). However, a greater percentage of patients treated with cyclophosphamide remained alive at time of analysis (66% vs. 46%).

Further, patients treated with tacrolimus and methotrexate experienced a shorter median time to platelet recovery (median, 19 days vs. 22 days) and absolute neutrophil count recovery (median, 16 days vs. 17 days). In both cases, however, the differences did not reach statistical significance.

Both groups had similar mean readmission rates during the first 100 days (cyclophosphamide, 0.8; tacrolimus/methotrexate, 0.77) and the first 6 months after transplantation (mean: cyclophosphamide, 1.1; tacrolimus/methotrexate, 1.3).

The groups also had similar rates of inpatient days in the first 100 days (cyclophosphamide, n = 40; tacrolimus/methotrexate, n = 42) and first 6 months (cyclophosphamide, n = 42; tacrolimus/methotrexate, n = 47).

“Our analysis highlights high-dose cyclophosphamide treatment as a compelling option for the prevention of GVHD, but with nuances,” Hossain said in a press release. “High-dose cyclophosphamide treatment may have significant positive impact on transplant outcomes and long-term costs of transplants. However, longer follow-up and analysis of a larger pool of patients will be required to further expand on the observations made in our study.” – by Cameron Kelsall

Reference:

Hossain NM, et al. Abstract 597. Presented at: BMT Tandem Meetings; Feb. 18-22, 2016; Honolulu.

Disclosure: HemOnc Today was unable to confirm the researchers’ relevant financial disclosures at the time of reporting.