Total Marrow and Lymphoid Irradiation with Post-Transplantation Cyclophosphamide for Patients with AML in Remission

Stein, Anthony S.; Malki, Monzr M. Al; Yang, Dongyun; Palmer, Joycelynne; Tsai, Ni‐Chun; Aldoss, Ibrahim; Ali, Haris; Aribi, Ahmed; Artz, Andrew; Dandapani, Savita; Farol, Len; Song, Hui; Liu, An; Nakamura, Ryotaro; Pullarkat, Vinod; Radany, Eric H.; Rosenthal, Joseph; Salhotra, Amandeep; Sanchez, James F.; Spielberger, Ricardo; Marcucci, Guido; Forman, Stephen J.; Wong, Jeffrey Y.C.

doi:10.1016/j.jtct.2022.03.025

Cited by 7 publications

(3 citation statements)

References 39 publications

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“…Disease relapse at 2 years was 16·7%. At a median follow up of 24.5 months, 2-year estimates of NRM, OS, relapse free survival, and GVHD-/relapse-free survival (GRFS) rate were 0%, 86·7%, 83·3%, and 59.3%, respectively ( 13 ). These results compare favorably to historical results at this center where GRFS was 39% at 2 years using TBI 13.2 Gy combined with Cy or etoposide and tacrolimus/sirolimus prophylaxis in patients with AML in remission ( 60 ).…”

Section: Review Of Clinical Resultsmentioning

confidence: 99%

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Total marrow irradiation (TMI): Addressing an unmet need in hematopoietic cell transplantation - a single institution experience review

Wong

Liu²,

Han³

et al. 2022

Front. Oncol.

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PurposeTMI utilizes IMRT to deliver organ sparing targeted radiotherapy in patients undergoing hematopoietic cell transplantation (HCT). TMI addresses an unmet need, specifically patients with refractory or relapsed (R/R) hematologic malignancies who have poor outcomes with standard HCT regimens and where attempts to improve outcomes by adding or dose escalating TBI are not possible due to increased toxicities. Over 500 patients have received TMI at this center. This review summarizes this experience including planning and delivery, clinical results, and future directions.MethodsPatients were treated on prospective allogeneic HCT trials using helical tomographic or VMAT IMRT delivery. Target structures included the bone/marrow only (TMI), or the addition of lymph nodes, and spleen (total marrow and lymphoid irradiation, TMLI). Total dose ranged from 12 to 20 Gy at 1.5-2.0 Gy fractions twice daily.ResultsTrials demonstrate engraftment in all patients and a low incidence of radiation related toxicities and extramedullary relapses. In R/R acute leukemia TMLI 20 Gy, etoposide, and cyclophosphamide (Cy) results in a 1-year non-relapse mortality (NRM) rate of 6% and 2-year overall survival (OS) of 48%; TMLI 12 Gy added to fludarabine (flu) and melphalan (mel) in older patients (≥ 60 years old) results in a NRM rate of 33% comparable to flu/mel alone, and 5-year OS of 42%; and TMLI 20 Gy/flu/Cy and post-transplant Cy (PTCy) in haplo-identical HCT results in a 2-year NRM rate of 13% and 1-year OS of 83%. In AML in complete remission, TMLI 20 Gy and PTCy results in 2-year NRM, OS, and GVHD free/relapse-free survival (GRFS) rates of 0%, 86·7%, and 59.3%, respectively.ConclusionTMI/TMLI shows significant promise, low NRM rates, the ability to offer myeloablative radiation containing regimens to older patients, the ability to dose escalate, and response and survival rates that compare favorably to published results. Collaboration between radiation oncology and hematology is key to successful implementation. TMI/TMLI represents a paradigm shift from TBI towards novel strategies to integrate a safer and more effective target-specific radiation therapy into HCT conditioning beyond what is possible with TBI and will help expand and redefine the role of radiotherapy in HCT.

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Section: Review Of Clinical Resultsmentioning

confidence: 99%

“…TMLI adds the major lymph node chains and spleen as target regions and is used in allogeneic HCT regimens (B) ( 11 ). In some studies, TMLI also includes the liver and brain to 12 Gy while other target regions (bone, lymph nodes and spleen) are escalated to 20 Gy (C) ( 12 , 13 ).…”

Section: Implementation Of Tmimentioning

confidence: 99%

Total marrow irradiation (TMI): Addressing an unmet need in hematopoietic cell transplantation - a single institution experience review

Wong

Liu²,

Han³

et al. 2022

Front. Oncol.

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“…Therefore, in recent years, PTCy has been expanded to matched transplants. Stein et al ( 17 ) have recently published a study testing TMLI at 20 Gy with PTCy for patients with acute myeloid leukemia in the first or second complete response undergoing matched donor allogeneic HCT. The patient safety lead-in segment followed a 3+3 dose expansion cohort of up to 12 additional patients.…”

Section: Tmi In Matched-related and Unrelated Hctmentioning

confidence: 99%

Total marrow irradiation in hematopoietic stem cell transplantation for hematologic malignancies

et al. 2023

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Total body irradiation (TBI) has been an essential component of the conditioning regimen in hematopoietic cell transplantation for many years. However, higher doses of TBI reduce disease relapse at the expense of more significant toxicities. Therefore, total marrow irradiation and total marrow and lymphoid irradiation have been developed to deliver organ-sparing targeted radiotherapy. Data from different studies show that TMI and TMLI can be safely administered in escalating doses in association with different chemotherapy conditioning regimen protocols, in situations with unmet needs, such as multiple myeloma, high-risk hematologic malignancies, relapsed or refractory leukemias, and elderly or frail patients, with low rates of transplant-related mortality. We reviewed the literature on applying TMI and TMLI techniques in autologous and allogeneic hematopoietic stem cell transplantation in different clinical situations.

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Incorporating intensity modulated total body irradiation into a Children's Oncology Group trial: Rationale, techniques, and safeguards

Milgrom,

Dandapani,

Wong

et al. 2024

Pediatric Blood & Cancer

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Historically, total body irradiation (TBI) has been delivered using static, parallel opposed photon beams (2D‐TBI). Recently, centers have increasingly used intensity‐modulated radiation therapy (IMRT) techniques for TBI. Relative to 2D‐TBI, IMRT can reduce doses to critical organs (i.e., lungs and kidneys) while delivering myeloablative doses to the rest of the body, so it may decrease the risk of toxicity while maintaining oncologic outcomes. Despite these potential benefits, delivering TBI using IMRT introduces new challenges in treatment planning and delivery. We describe the extensive experience with IMRT‐based TBI at Stanford University and City of Hope Cancer Center. These groups, and others, have reported favorable clinical outcomes and have developed methods to optimize treatment planning and delivery. A critical next step is to evaluate the broader adoption of this approach. Therefore, IMRT‐based TBI will be incorporated into a prospective, multi‐institutional Children's Oncology Group study with careful procedures and safeguards in place.

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Total Marrow and Lymphoid Irradiation with Post-Transplantation Cyclophosphamide for Patients with AML in Remission

Cited by 7 publications

References 39 publications

Total marrow irradiation (TMI): Addressing an unmet need in hematopoietic cell transplantation - a single institution experience review

Total marrow irradiation (TMI): Addressing an unmet need in hematopoietic cell transplantation - a single institution experience review

Total marrow irradiation in hematopoietic stem cell transplantation for hematologic malignancies

Incorporating intensity modulated total body irradiation into a Children's Oncology Group trial: Rationale, techniques, and safeguards

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