Association of Reduced-Intensity Conditioning Regimens With Overall Survival Among Patients With Non-Hodgkin Lymphoma Undergoing Allogeneic Transplant

Ghosh, Nilanjan; Ahmed, Sairah; Ahn, Kwang Woo; Khanal, Manoj; Litovich, Carlos; Aljurf, Mahmoud; Bacher, Vera Ulrike; Bredeson, Christopher; Epperla, Narendranath; Farhadfar, Nosha; Freytes, César O.; Ganguly, Siddhartha; Haverkos, Bradley M.; Inwards, David J.; Kamble, Rammurti T.; Lazarus, Hillard M.; Lekakis, Lazaros J.; Murthy, Hemant S.; Nishihori, Taiga; Ramakrishnan, Praveen; Rizzieri, David A.; Yared, Jean A.; Kharfan‐Dabaja, Mohamed A.; Sureda, Anna; Hamadani, Mehdi

doi:10.1001/jamaoncol.2020.1278

Cited by 45 publications

(29 citation statements)

References 33 publications

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“…34 The benefits of intensifying conditioning intensity in lymphoma patients are debatable. Similar to previous studies on allo-HCT in other NHL subtypes, 22,[44][45][46][47][48][49] the current study does not show an advantage of high intensity conditioning regimens for the first time also for mature nodal T-cell NHL in a large dataset.…”

Section: Discussionsupporting

confidence: 87%

Outcome of allogeneic transplantation for mature T-cell lymphomas: impact of donor source and disease characteristics

et al. 2022

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Mature T-cell lymphomas constitute the most common indication of allogeneic hematopoietic cell transplantation (allo-HCT) in lymphomas. Large studies evaluating contemporary outcomes of allo-HCT in mature T-cell lymphomas, relative to commonly used donor sources are not available. Included in this registry study were adult patients who had undergone allo-HCT for anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), or peripheral T-cell lymphoma-NOS (PTCL-NOS) between 2008 and 2018. HCT platforms compared were post-transplant cyclophosphamide-based haploidentical (haplo-) HCT, matched sibling donor (MSD) HCT, matched unrelated donor HCT with in-vivo T-cell depletion (MUD TCD+), and MUD HCT without TCD (MUD TCD-). Co-primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included non-relapse mortality (NRM), and relapse/progression incidence (RI). 1942 patients were eligible (haplo-HCT 237; MSD 911; MUD-TCD+ 468; MUD TCD- 326). Cohorts were comparable for baseline characteristics except higher proportions of patients with decreased performance status (PS) and marrow graft recipients in the haplo-HCT group. On univariate and multivariate comparisons, OS and PFS, RI, and NRM were not significantly different between haplo-HCT, MSD, MUD-TCD+, and MUD-TCD- cohorts, with 3-year OS and PFS of 60%, 63%, 59%, and 64%; and 50%, 50%, 48%, and 52%, respectively. Significant predictors of inferior OS and PFS on multivariate analysis were active disease status at HCT and decreased PS. AITL was associated with significantly reduced relapse risk and better PFS compared to PTCL-NOS. Allo-HCT can provide durable PFS in patients with mature T-cell lymphoma. Outcomes of haplo-HCT were comparable to that of matched donor allo-HCT.

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Section: Discussionsupporting

confidence: 87%

Outcome of allogeneic transplantation for mature T-cell lymphomas: impact of donor source and disease characteristics

et al. 2022

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“…In addition, the CIBMTR recently published data regarding the impact of various RIC regimens on HSCT outcomes for NHL patients, and patients who received fludarabine, cyclophosphamide, and 200 cGy of TBI conditioning were among those with the best outcomes, which were superior to outcomes of patients who received more intensive fludarabine-melphalan 140 mg/m 2 conditioning. 28 Our findings suggest that, unlike patients with other NHL histologies, patients with CLL might not benefit from TBI-containing regimens. A previous study from Denmark reported that patients with CLL had lower response rates to low doses of radiation at irradiated sites compared with patients with other indolent NHL histologies.…”

Section: Discussionmentioning

confidence: 66%

Reduced-intensity conditioning hematopoietic stem cell transplantation for chronic lymphocytic leukemia and Richter’s transformation

Lahoud¹,

Devlin

Maloy³

et al. 2021

Blood Advances

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Allogeneic hematopoietic stem cell transplantation (HSCT) may potentially cure patients with chronic lymphocytic leukemia (CLL) and Richter’s transformation (CLL-RT) or CLL without RT, but the impact of novel agents on HSCT is unclear. CLL-RT patients have a grave prognosis, and their outcomes after HSCT are uncertain. We conducted a retrospective analysis of all 58 CLL patients, including 23 CLL-RT patients, who underwent reduced intensity conditioning (RIC) HSCT at Memorial Sloan Kettering Cancer Center (New York, NY) between September 2006 and April 2017. With a median follow-up of 68 months (range, 24-147 months), 5-year progression-free survival (PFS) was 40% (95% confidence interval [CI], 28%-56%), and overall survival (OS) was 58% (95% CI, 48%-74%). The 1-year graft-versus-host disease/relapse-free survival (GRFS) was 38% (95% CI, 25%-50%). Patients with CLL-RT and CLL patients without RT had comparable outcomes. In both cohorts, treatment-sensitive response and ≤3 previous lines of therapy produced superior PFS and OS. Outcomes were agnostic to adverse cytogenetic and molecular features. Novel agents did not have a negative impact on HSCT outcomes. Total body irradiation (TBI)-containing RIC yielded inferior PFS, OS, and GRFS. CLL-RT patients older than age 55 years who had an HSCT Comorbidity Index score of ≥2 demonstrated inferior OS. This study, which is the largest series of RIC-HSCT for patients with CLL-RT, provides evidence supporting RIC-HSCT in early remission courses for patients with CLL-RT and poor-risk CLL patients. TBI-containing RIC should be considered with caution.

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“…This suggests that the high rate of severe CRS observed in our cohort may be related to the unique combination of using PBSC grafts with FluMel conditioning. One recent study found a higher rate of NRM and decreased OS in patients with NHL receiving FluMel conditioning for allogeneic HCT compared to udarabine and busulfan-based conditioning 13 , whereas another cohort of patients with lymphoma undergoing haplo-HCT with udarabine and cyclophosphamide conditioning did not suffer increased NRM or reduced OS 14 .…”

Section: Discussionmentioning

confidence: 99%

Increased Early Mortality After Fludarabine and Melphalan Conditioning with Peripheral Blood Grafts in Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide

Eastburg

Russler‐Germain

DiPersio

et al. 2021

Preprint

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Due to the evolving use of haploidentical donor grafts in hematopoietic cell transplantation, there is increased need to better understand the risks and benefits of using bone marrow versus peripheral blood grafts, as well as how specific pre-transplantation conditioning regimens impact patient safety and treatment outcomes. We performed a retrospective analysis of 38 patients at two centers who specifically underwent haploidentical hematopoietic cell transplantation using fludarabine plus melphalan-based conditioning regimens with post-transplant cyclophosphamide and peripheral blood donor grafts. We observed an unexpectedly high rate of early non-relapse mortality of 21% at 100 days and 34% at 1-year. In addition, 40% of all patients suffered from severe cytokine release syndrome and 45% of all patients suffered from kidney injury, often necessitating renal replacement therapy. The poor outcomes with 1-year overall survival of 34%, disease-free survival of 29%, and non-relapse mortality of 34% motivate us to reconsider the appropriateness of the combination of fludarabine and melphalan conditioning with T-cell replete peripheral blood grafts in the setting of haploidentical hematopoietic cell transplant with post-transplant cyclophosphamide.

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Association of Reduced-Intensity Conditioning Regimens With Overall Survival Among Patients With Non-Hodgkin Lymphoma Undergoing Allogeneic Transplant

Cited by 45 publications

References 33 publications

Outcome of allogeneic transplantation for mature T-cell lymphomas: impact of donor source and disease characteristics

Outcome of allogeneic transplantation for mature T-cell lymphomas: impact of donor source and disease characteristics

Reduced-intensity conditioning hematopoietic stem cell transplantation for chronic lymphocytic leukemia and Richter’s transformation

Increased Early Mortality After Fludarabine and Melphalan Conditioning with Peripheral Blood Grafts in Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide

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