Risk Assessment in Adult T Cell Leukemia/Lymphoma Treated with Allogeneic Hematopoietic Stem Cell Transplantation

Yoshimitsu, Makoto; Tanosaki, Ryuji; Katô, Kôji; Ishida, Takashi; Choi, Ilseung; Takatsuka, Yuichi; Fukuda, Takahiro; Eto, Tetsuya; Hidaka, Masaaki; Uchida, Naoyuki; Miyamoto, Toshihiro; Nakashima, Yasuhiro; Moriuchi, Yukiyoshi; Nagafuji, Koji; Miyazaki, Yasuhiko; Ichinohe, Tatsuo; Takanashi, Minoko; Atsuta, Yoshiko; Utsunomiya, Atae

doi:10.1016/j.bbmt.2017.11.005

Cited by 14 publications

(10 citation statements)

References 34 publications

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“…Further, we showed that hematopoietic cell transplantation-specific comorbidity index (HCT-CI; Sorror et al, 2005) and EBMT score (Gratwohl et al, 2009) at transplant were reliable prognostic factors in patients with ATL who underwent allo-HCT (Tokunaga et al, 2017). However, the EBMT score was not associated with the risk of non-relapse mortality (NRM) because about 95% of patients with ATL who underwent allo-HCT were over than 40 years of age in the Japanese TRUMP database (Yoshimitsu et al, 2018a). We attempted to develop another new ATL HCT prognostic index (ATL-HCT-PI).…”

Section: Development Of Allo-hct For Atlmentioning

confidence: 99%

“…We attempted to develop another new ATL HCT prognostic index (ATL-HCT-PI). We determined three independent risk factors, including optimized HCT-CI, donor–recipient sex combination (female donor–male recipient), and older age (≥64 years; Yoshimitsu et al, 2018a). By using these three risk factors, we divided patients into 3 risk groups, namely low, intermediate, and high risk, and then developed a new ATL-HCT-PI, which could be used to stratify NRM and OS rates in patients with ATL according to the three risk groups (2-year NRM of 22.0, 27.7, and 44.4%, and 2-year OS of 47.3, 39.1, and 15.7% for ATL-HCT-PI low-, intermediate-, and high-risk patients, respectively; Yoshimitsu et al, 2018a).…”

Section: Development Of Allo-hct For Atlmentioning

confidence: 99%

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Progress in Allogeneic Hematopoietic Cell Transplantation in Adult T-Cell Leukemia-Lymphoma

Utsunomiya

2019

Front. Microbiol.

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The prognosis of aggressive adult T-cell leukemia-lymphoma (ATL) remains poor because of frequent infections and drug resistance. Dose-intensified chemotherapy followed by autologous stem cell transplantation failed to improve the prognosis of patients with ATL; however, we first revealed that allogeneic hematopoietic cell transplantation (allo-HCT) might improve their prognosis. We showed that reducedintensity stem cell transplantation using peripheral blood was feasible for elderly patients. Further, the prognosis of patients in remission, who receive cord blood transplantation, has been recently improved and is equivalent to that of patients who receive transplants from other stem cell sources. As for the timing of HCT, the patients who underwent transplantation early showed better outcomes than those who underwent transplantation late. Based on the analysis of patients with aggressive ATL, including those who received transplants, we identified five prognostic factors for poor outcomes: acute-type ATL, poor performance status, high soluble interleukin-2 receptor levels, hypercalcemia, and high C-reactive protein level. Next, we developed a new prognostic index: the modified ATL-PI. The overall survival (OS) rates were significantly higher in patients who underwent allo-HCT than those who did not in the intermediate and high-risk groups stratified using the modified ATL-PI. Two new anti-cancer agents, mogamulizumab and lenalidomide, were recently approved for ATL patients in Japan. They are expected to induce longer survival in ATL patients when administered along with transplantation. However, a retrospective analysis that the risk of severe, acute, and corticosteroid-refractory graft-versus-host disease was higher in patients who received mogamulizumab before allo-HCT, and that mogamulizumab might increase the transplant-related mortality (TRM) rates and decrease the OS rates compared to those of patients who did not receive mogamulizumab. However, our recent study showed that administration of mogamulizumab before allo-HCT tended to improve the survival of patients with ATL. In conclusion, allo-HCT procedures for patients with aggressive Frontiers in Microbiology | www.frontiersin.org October 2019 | Volume 10 | Article 2235 Utsunomiya Allo-HCT in ATL ATL have considerably progressed and have helped improve the prognosis of these patients; however, many concerns still remain to be resolved. Further development of allo-HCT by using new molecular targeting agents is required for the improvement of cure rates in patients with ATL.

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Section: Development Of Allo-hct For Atlmentioning

confidence: 99%

Section: Development Of Allo-hct For Atlmentioning

confidence: 99%

Progress in Allogeneic Hematopoietic Cell Transplantation in Adult T-Cell Leukemia-Lymphoma

Utsunomiya

2019

Front. Microbiol.

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“…The cumulative incidences of NRM at 100 days and 1 year after transplantation were 19% (95% CI, 2%‐36%) and 42% (95% CI, 16%‐69%), respectively (Figure A). Recently, Yoshimitsu et al established ATL‐HCT‐PI, a predictive scoring system for NRM in allo‐HCT for ATL patients. ATL‐HCT‐PI consists of three factors: revised HCT‐CI, sex combination (female donor and male recipient), and age 64 years or older.…”

Section: Resultsmentioning

confidence: 99%

“…Another reason for unfavorable OS after allo‐HSCT was higher NRM in our study. Yoshimitsu et al recently reported that three factors, namely, revised HCT‐CI, sex combination (female donor and male recipient), and age 64 years or older, were useful for predicting NRM in ATL patients after allo‐HCT (ATL‐HCT‐PI). In our study, even the low‐risk group defined by ATL‐HCT‐PI had a high NRM of 58%, with the following causes of death: disease relapse/progression (two cases), HHV‐6 encephalopathy, bacterial infection, thrombotic microangiopathy (TMA), and lymphoproliferative disorder (each one case).…”

Section: Discussionmentioning

confidence: 99%

Outcome of allogeneic hematopoietic cell transplantation in patients with adult T‐cell leukemia

Kamiunten

Sekine

Kameda

et al. 2018

Hematological Oncology

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Adult T‐cell leukemia/lymphoma (ATL) is an aggressive peripheral T‐cell neoplasm, and the outcome of patients with ATL after chemotherapy is poor. Allogeneic hematopoietic stem‐cell transplantation (allo‐HSCT) is a curative treatment modality for ATL, and four factors, namely, age > 50 years, male recipient, lack of complete remission at transplantation, and transplantation of cord blood, were previously shown to be associated with poor survival. We retrospectively analyzed the outcome of 21 patients with ATL who had undergone allo‐HSCT at our hospital during a 3‐year period. Of 21 patients, all had at least one of the above risk factors, and 18 had two or more. With a median follow‐up of 19.7 months for living patients, the 1‐ and 2‐year overall survival (OS) rates after transplantation were 34% and 27%, respectively. All relapse/progression events occurred within 1 year after allo‐HSCT, and the cumulative incidence of relapse/progression at 1 year after allo‐HSCT was 46.9%. The 100‐day and 1‐year nonrelapse mortality (NRM) rates were 19% and 42%, respectively. No significant difference in OS was observed between myeloablative and reduced‐intensity conditioning regimens. The 3‐year OS (27%) of ATL patients who received allo‐HSCT and who had at least one adverse factor was somewhat poorer than the 3‐year OS of 33% identified in a nationwide study of allo‐HSCT in ATL patients in Japan. The high relapse/progression and NRM rates are major problems to be solved to achieve better outcome.

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“…Most data favoring alloHSCT over chemotherapy alone originate from retrospective analyses, are limited by selection bias, and show a relatively high transplant-related mortality (TRM) [3,6]. Nevertheless, alloHSCT is the only treatment modality that can achieve long-term remissions or cure, especially for aggressive subtypes, and has demonstrated potential survival advantage [14,15]. Hence, upfront alloHSCT has become the preferred strategy in acute and lymphomatous subtype patients who are transplant-eligible [16,17].…”

Section: Biol Blood Marrow Transplant 25 (2019) E199àe203mentioning

confidence: 99%

Barriers to Allogeneic Hematopoietic Stem Cell Transplantation for Human T Cell Lymphotropic Virus 1–Associated Adult T Cell Lymphoma–Leukemia in the United States: Experience from a Large Cohort in a Major Tertiary Center

Herrera

Kornblum

Acuña-Villaorduña

et al. 2019

Biology of Blood and Marrow Transplantation

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In the United States adult T cell lymphomaÀleukemia (ATLL) carries a dismal prognosis and mainly affects immigrants from human T cell lymphotropic virus 1 endemic areas. Allogeneic hematopoietic stem cell transplant (alloHSCT) can be effective and is recommended as an upfront treatment in the National Comprehensive Cancer Network guidelines. We studied the barriers to alloHSCT in one of the largest ATLL populations in the United States. Comprehensive chart and donor registry reviews were conducted for 88 ATLL patients treated at Montefiore Medical Center from 2003 to 2018. Among 49 patients with acute and 32 with lymphomatous subtypes, 48 (59.5%) were ineligible for alloHSCT because of early mortality (52%), loss to follow-up (21%), uninsured status (15%), patient declination (10%), and frailty (2%). Among 28 HLA-typed eligible patients (34.6%), matched related donors were identified for 7 (25%). A matched unrelated donor (MUD) search yielded HLA-matched in 2 patients (9.5%), HLA mismatched in 6 (28.5%), and no options in 13 (62%). Haploidentical donors were identified for 6 patients (46%) with no unrelated options. There were no suitable donors for 7 (25%) alloHSCT-eligible patients. The main limitation for alloHSCT after donor identification was death from progressive disease (82%). AlloHSCT was performed in 10 patients (12.3%) and was associated with better relapse-free survival (26 versus 11 months, P = .04) and overall survival (47 versus 10 months, P = .03). Early mortality and progressive disease are the main barriers to alloHSCT, but poor follow-up, uninsured status, and lack of suitable donor, including haploidentical, are also substantial limitations that might disproportionally affect this vulnerable population. AlloHSCT can achieve long-term remissions, and strategies aiming to overcome these barriers are urgently needed to improve outcomes in ATLL.

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Risk Assessment in Adult T Cell Leukemia/Lymphoma Treated with Allogeneic Hematopoietic Stem Cell Transplantation

Cited by 14 publications

References 34 publications

Progress in Allogeneic Hematopoietic Cell Transplantation in Adult T-Cell Leukemia-Lymphoma

Progress in Allogeneic Hematopoietic Cell Transplantation in Adult T-Cell Leukemia-Lymphoma

Outcome of allogeneic hematopoietic cell transplantation in patients with adult T‐cell leukemia

Barriers to Allogeneic Hematopoietic Stem Cell Transplantation for Human T Cell Lymphotropic Virus 1–Associated Adult T Cell Lymphoma–Leukemia in the United States: Experience from a Large Cohort in a Major Tertiary Center

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