March 13, 2020
2 min read

Myeloablative fractionated busulfan feasible as pre-HSCT regimen for older patients

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A myeloablative fractionated busulfan regimen with post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis appeared feasible for older patients with hematologic malignancies, according to results of a single-arm phase 2 study presented at TCT | Transplantation & Cellular Therapy Meetings.

The regimen appeared associated with low rates of severe acute GVHD, chronic GVHD and nonrelapse mortality, as well as promising OS, results showed.

“The idea underlying this protocol is extremely simple and very promising,” Uday R. Popat, MD, professor in the department of stem cell transplantation in the division of cancer medicine at The University of Texas MD Anderson Cancer Center, said during a presentation. “You can reduce the toxicity and attendant mortality of [an] intense regimen by simply giving it over a longer period.”

Patients who undergo hematopoietic stem cell transplantation typically receive a conditioning regimen over 4 to 6 days prior to transplantation. Popat and colleagues sought to determine whether a myeloablative dose of busulfan delivered over a 3-week period would reduce nonrelapse mortality and toxicity without impacting relapse among adults with hematologic malignancies, adequate organ function, and 8/8 HLA-matched related or unrelated donors.

A myeloablative fractionated busulfan regimen with post-transplant cyclophosphamide-based GVHD prophylaxis appeared feasible for older patients with hematologic malignancies.

The researchers enrolled 52 patients (median age, 62 years; range, 39-69), including 25 (48%) with acute myeloid leukemia or myelodysplastic syndrome, 26 (50%) with chronic myeloid leukemia or myeloproliferative disorders, and one (2%) with multiple myeloma.

Most patients (65%) had intermediate disease risk index (DRI), whereas 27% had high DRI, 6% had low DRI and 2% had very high DRI. An equal number of patients had an HSCT comorbidity index of 1 to 2 (44%) and 3 or greater (44%).

Thirty-two patients (62%) had an unrelated donor.

Patients received a fixed 80 mg/m² dose of busulfan 20 days and 13 days prior to transplant. They received 40 mg/m² fludarabine 6 days and 2 days before transplant, followed by busulfan dosed to reach the target area under the curve of 20,000 mol/min for the entire course.

GVHD prophylaxis consisted of cyclophosphamide dosed at 50 mg/kg on days 3 and 4 after transplant, along with tacrolimus. Some unrelated donor recipients also received mycophenolate mofetil.

Nonrelapse mortality at day 100 served as the primary endpoint.

Median follow-up was 14 months (range, 3-23).

Results showed nonrelapse mortality of 1.9% at day 100 and 8% at 1 year. Researchers reported a 1-year OS rate of 83% (95% CI, 73-95), a 1-year PFS rate of 78% (95% CI, 67-91) and a 1-year relapse rate of 14% (95% CI, 4-24).


Researchers observed no graft failures. Median time to neutrophil engraftment was 17 days (range, 13-33).

Median time to platelet engraftment of at least 20,000/µL (n = 45) was 24 days (range, 9-266).

Patients with low or intermediate DRI were significantly more likely than those with high or very high DRI to survive 1 year (94% vs. 53%; P = .001)

Rates of acute GVHD at day 100 were 37% (95% CI, 23-50) for grade 2 to grade 4 and 6% (95% CI, 0-12) for grade 3 to grade 4. Additionally, researchers observed a 1-year chronic GVHD rate of 9% (95% CI, 0-17) and 1-year extensive chronic GVHD rate of 7% (95% CI, 0-14).

“[These] data obviously [need] to be confirmed by others,” Popat said. “I think this needs to be done as a multicenter study in the phase 2 or phase 3 setting comparing it to these results.” – by John DeRosier


Popat UR, et al. Abstract 6. Presented at: TCT | Transplantation & Cellular Therapy Meetings; Feb. 19-23, 2020; Orlando.

Disclosures: Popat reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.