Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation

Brunstein, Claudio G.; Pasquini, Marcelo C.; Kim, Soyoung; Fei, Mingwei; Adekola, Kehinde; Ahmed, Ibrahim; Aljurf, Mahmoud; Agrawal, Vaibhav; Auletta, Jeffery J.; Battiwalla, Minoo; Bejanyan, Nelli; Bubalo, Joseph; Černý, Jan; Chee, Lynette; Ciurea, Stefan O.; Freytes, César O.; Gadalla, Shahinaz M.; Gale, Robert Peter; Ganguly, Siddhartha; Hashmi, Shahrukh K.; Hematti, Peiman; Holmberg, Leona; Lahoud, Oscar; Landau, Heather; Lazarus, Hillard M.; Lima, Marcos de; Maziarz, Richard T.; Nishihori, Taiga; Norkin, Maxim; Olsson, Richard F.; Reshef, Ran; Rotz, Seth J.; Savani, Bipin N.; Schouten, Harry C.; Seo, Sachiko; Wirk, Baldeep; Yared, Jean A.; Mineishi, Shin; Rogosheske, John; Perales, Miguel Angel

doi:10.1016/j.bbmt.2018.11.005

Cited by 10 publications

(7 citation statements)

References 16 publications

(18 reference statements)

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“…Using dose limiting to prevent increased toxicity without loss in antitumor effect seems feasible due to previous results on the association of dose/weight relation with adverse side effects in DLBCL patients undergoing conditioning chemotherapy for auto-HSCT[44]. Additionally, in a large recently published study in lymphoma and multiple myeloma patients undergoing auto-HSCT, no increased relapse rates were observed concerning dose reductions[45].…”

Section: Discussionmentioning

confidence: 99%

Obesity is associated with an impaired survival in lymphoma patients undergoing autologous stem cell transplantation

et al. 2019

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Autologous hematopoietic stem cell transplantation (auto-HSCT) provides a potentially curative treatment option for relapsed and refractory lymphomas. Obesity displays an emerging epidemic risk factor for global mortality and is associated with an increased mortality in cancer patients. To date, the impact of obesity on the outcome of lymphoma patients undergoing auto-HSCT is understudied. We conducted a retrospective single-center study assessing 119 lymphoma patients who underwent auto-HSCT. Overall survival (OS) served as the primary endpoint whereas progression free survival (PFS), cumulative incidence of non-relapse related mortality (NRM) and cumulative incidence of relapse were analyzed as secondary endpoints. Obese patients (Body mass index, BMI≥30) had significantly lower OS (45.3% vs. 77.9%; p = 0.005) and PFS (29.8% vs. 67.2%; p<0.001) compared to non-obese patients at 48 months post-transplantation. The cumulative incidence of NRM displayed no significant differences while the cumulative incidence of relapse was significantly increased in patients with BMI≥30 (66.2% vs. 21.5%; p<0.001). Patients with a BMI<25 and overweight patients (BMI 25–30; 76.1% vs. 80.9%; p = 0.585), showed no significant difference in OS, whereas patients with BMI≥30 exhibited significant lower OS when compared to either of both groups (76.1% vs. 45.3%; p = .0.021 and 80.9% vs. 45.3%; p = 0.010). Furthermore, in a multivariate analysis, obesity was identified as an independent risk factor for death (Hazard ratio 2.231; 95% CI 1.024 to 4.860; p = 0.043). Further studies are needed to evaluate the reasons for the higher relapse rate causing higher mortality in obese patients.

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Section: Discussionmentioning

confidence: 99%

Obesity is associated with an impaired survival in lymphoma patients undergoing autologous stem cell transplantation

et al. 2019

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“…During the timeframe correlated with the day -1 cohort, our standard of care changed to using actual body weight for melphalan dosing versus previously using adjusted body weight in obese patients, based on new literature. 10 Moreover, our institution switched from propylene glycol (PG)-free melphalan (Evomela®) to generic (Alkeran®) based on significant cost savings. Supportive care included oral cryotherapy using ice chips (15 minutes prior, during, and at least 60 minutes after melphalan infusion), standard antimicrobial prophylaxis (e.g., viral, bacterial, fungal, pneumocystis jirovecii pneumonia) starting on day -1, and filgrastim starting on day +3.…”

Section: Methodsmentioning

confidence: 99%

Melphalan on day -1 versus day -2 in patients with plasma cell disorders undergoing autologous stem cell transplant

Watson

Shah

Shalhoub

et al. 2022

J Oncol Pharm Pract

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High-dose melphalan-based autologous stem cell transplant (ASCT) remains a standard of care for plasma cell disorders (PCDs). Currently, there is variability in the literature surrounding the timing of melphalan administration to avoid potential cytotoxic effects, although the administration has been safely proposed when given at least 8 hours prior to stem cell infusion. The objectives of this study were to assess differences in safety and efficacy outcomes between day -1 and day -2 single-dose melphalan administration in patients undergoing ASCT for PCDs. A retrospective chart review was performed at our institution comparing patients receiving melphalan on day -1 to an equal number of patients receiving melphalan on day -2. The primary endpoint was time to neutrophil engraftment from stem cell infusion. Univariate analyses were performed. Mean time to neutrophil engraftment from stem cell infusion was identical at 10.7 days for both cohorts ( p = 0.88). Mean time to platelet engraftment from stem cell infusion was shorter with day -1 administration (17.4 vs. 18.6 days, p = 0.06). Mean time to neutrophil and platelet engraftment from melphalan infusion were significantly shorter with day -1 administration. Similar outcomes were observed for length of hospitalization, infection- and mucositis-related toxicities, hematologic response, transplant-related mortality, and overall survival. Our findings show no difference in time to neutrophil engraftment from stem cell infusion and a trend toward shorter time to platelet engraftment with day -1 administration. Based on our study, day -1 melphalan administration is an acceptable and safe practice.

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“…In particular, auto-HSCT has been implemented in elderly patients or patients with comorbidities therefore with caution, 3,4 using low-dose conditioning regimens. [5][6][7] For this reason, several comorbidity-assessment scores (e.g., HCT-CI) have been developed over the years, to predict outcomes in patients with hematological malignancies undergoing allogeneic stem cell transplantation (allo-HSCT). 8,9 The HCT-CI-score has been also successfully implemented in patients undergoing auto-HSCT 10,11 and potentially adapt conditioning protocols to the individual risks of each patient.…”

Section: Introductionmentioning

confidence: 99%

Identification of clinical factors impacting outcome in patients undergoing autologous hematopoietic cell transplantation after BEAM and TEAM conditioning

Gherman,

Ewald,

Ihorst

et al. 2023

European J of Haematology

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Organ dysfunction, including pulmonary function impairment, plays a key role in the choice of conditioning chemotherapy before autologous hematopoietic stem cell transplantation (auto‐HSCT). Replacement of BCNU/carmustine as part of BEAM (BCNU/carmustine, etoposide, cytarabine, and melphalan) conditioning protocol by thiotepa (TEAM) reduces pulmonary toxicity while maintaining efficacy. We retrospectively analyzed the association of clinical characteristics, comorbidities, and organ function with outcomes after conditioning with BEAM or TEAM. Three hundred ninety‐six patients undergoing auto‐HSCT (n = 333 with BEAM; n = 63 with TEAM) at our institution between 2008 and 2021 were included in this study. In the multivariate analysis, CO‐diffusion capacity corrected for hemoglobin (DLCOcSB) ≤ 60% of predicted, progressive disease (PD) before auto‐HSCT, Karnofsky performance score (KPS) ≤ 80%, HCT‐CI score ≥ 4, and cardiac disease before auto‐HSCT were associated with decreased overall survival (OS) in patients treated with BEAM. In contrast, only PD before auto‐HSCT was identified in patients treated with TEAM. Patients conditioned with BEAM and DLCOcSB ≤ 60% had higher non‐relapse mortality, including pulmonary cause of death. In summary, we have identified clinical and pulmonary risk factors associated with worse outcomes in patients conditioned with BEAM compared to TEAM. Our data suggest TEAM conditioning as a valid alternative for patients with comorbidities, including pulmonary dysfunction and/or poorer performance scores, before auto‐HSCT.

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Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation

Cited by 10 publications

References 16 publications

Obesity is associated with an impaired survival in lymphoma patients undergoing autologous stem cell transplantation

Obesity is associated with an impaired survival in lymphoma patients undergoing autologous stem cell transplantation

Melphalan on day -1 versus day -2 in patients with plasma cell disorders undergoing autologous stem cell transplant

Identification of clinical factors impacting outcome in patients undergoing autologous hematopoietic cell transplantation after BEAM and TEAM conditioning

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