Reduced-Intensity Conditioning with Fludarabine, Melphalan, and Total Body Irradiation for Allogeneic Hematopoietic Cell Transplantation: The Effect of Increasing Melphalan Dose on Underlying Disease and Toxicity

Abstract

A B S T R A C T Disease relapse and toxicity are the shortcomings of reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (alloHCT). We hypothesized that adding total body irradiation (TBI) to and decreasing melphalan (Mel) from a base RIC regimen of fludarabine (Flu) and Mel would increase cytoreduction and improve disease control while decreasing toxicity. We performed a phase II trial of Flu 160 mg/m 2 , Mel 50 mg/m 2 , and TBI 400 cGy (FluMelTBI-50, n = 61), followed by a second phase II trial of Flu 160 mg/m 2 , Mel 75 mg/m 2 , and TBI 400 cGy (FluMelTBI-75, n = 94) as RIC for alloHCT. Outcomes were compared with a contemporaneous cohort of 162 patients who received Flu 125 mg/m 2 and Mel 140 mg/m 2 . Eligibility criteria were equivalent for all 3 regimens. All patients were ineligible for myeloablative/intensive conditioning. The median (range) follow-up for all patients was 51 (15 to 103) months. Day 100 donor lymphoid chimerism and transplant-related mortality, neutrophil and platelet engraftment, acute and chronic graft versus host disease incidence, overall survival (OS), and progression-free survival (PFS) were equivalent between FluMel, FluMelTBI-50, and FluMelTBI-75. Stomatitis was decreased for FluMelTBI versus FluMel (P < .01). PFS for patients not in complete remission on alloHCT was improved for FluMelTBI-75 versus FluMel (P = .03). On multivariate analysis, OS (P = .05) and PFS (P = .05) were significantly improved for FluMelTBI-75 versus FluMel. FluMelTBI-75 is better tolerated than FluMel, with improved survival and disease control.

The Incidence of Severe Oral Mucositis and Taste Disturbance in Patients Undergoing Different Conditioning Regimens in Haematopoietic Stem Cell Transplantation

“…Our study collaborates this, and suggested superiority of PTCy in terms of OM prevention. Although melphalan dose has been shown to predict OM in one study [17],…”

“…Methotrexate (MTX) as an immunosuppressant, and its dose, are consistently reported as a risk factor for OM [14,16,9]. Melphalan is known to cause OM and its dose and administration method appear to affect OM [17,18]. Only a small number of OM studies control for these confounding factors, which may affect OM more than the interventions tested.…”

Managing the Oral Health of Cancer Patients During the COVID-19 Pandemic: Perspective of a Dental Clinic in a Cancer Center

“…Managing the oral health of cancer patients requires timely coordination of care between surgeons, radiation oncologists, medical oncologists, radiologists, pathologists, dentists and maxillofacial prosthodontists. For example, we have previously documented that stem cell transplant patients may have a narrow window of adequate disease control for successful transplantation [ 26 ]. Similarly, the time from a head and neck cancer diagnosis to the initiation of radiation therapy correlates with survival [ 27 ].…”

Maintain Efficacy and Spare Toxicity: Traditional and New Radiation-Based Conditioning Regimens in Hematopoietic Stem Cell Transplantation

“…Less intensive conditioning regimens have been developed in order to offer HCT to unfit patients [ 107 , 108 , 109 , 110 ]. TMI/TMLI then has the potential to improve the outcome, with similar toxicities, when in combination with chemotherapy in the setting of RIC.…”