Comparison of outcomes after allogeneic hematopoietic stem cell transplantation in patients with follicular lymphoma, diffuse large B‐cell lymphoma associated with follicular lymphoma, or <i>de novo</i> diffuse large B‐cell lymphoma

Tada, Kohei; Kim, Sung Won; Asakura, Yoshitaka; Hiramoto, Nobuhiro; Yakushijin, Kimikazu; Kurosawa, Saiko; Tajima, Kinuko; Mori, Shin Ichiro; Heike, Yuji; Tanosaki, Ryuji; Maeshima, Akiko Miyagi; Taniguchi, Hirokazu; Furuta, Koh; Kagami, Yoshikazu; Matsuno, Yoshihiro; Tobinai, Kensei; Takaue, Yoichi; Fukuda, Takahiro

doi:10.1002/ajh.23246

Cited by 13 publications

(9 citation statements)

References 29 publications

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“…Associations of DEL status with outcomes after allogeneic HCT for t-FL have not been well examined to date. We expected to find better PFS rates in DEL patients with t-FL compared with those with de novo DLBCL, given that some studies have shown stronger graft-versus-lymphoma effects against follicular lymphoma compared with de novo DLBCL [28,29]. Contrary to this expectation, however, our results show that DEL was associated with low PFS rates both in patients with t-FL and in those with de novo DLBCL.…”

Section: Discussioncontrasting

confidence: 80%

Double-Expressor Lymphoma Is Associated with Poor Outcomes after Allogeneic Hematopoietic Cell Transplantation

Kawashima¹,

Inamoto²,

Maeshima

et al. 2018

Biology of Blood and Marrow Transplantation

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Double-expressor lymphoma (DEL) is a diffuse large B cell lymphoma that exhibits co-expression of MYC and BCL2 proteins by immunohistochemistry. Patients with double-expressor lymphoma have a poor prognosis after standard chemoimmunotherapy or after high-dose chemotherapy with autologous transplantation, but the prognostic impact of DEL after allogeneic hematopoietic cell transplantation has not been well characterized. We retrospectively analyzed 60 consecutive patients with de novo diffuse large B cell lymphoma or transformed follicular lymphoma who underwent allogeneic transplantation at our center and had available immunohistochemistry data. Thirty-seven patients (62%) had DEL. The 2-year progression-free and overall survival rates were lower in patients with DEL than in those without DEL (20% versus 78%; overall P <.001 and 46% versus 77%; overall P = .016, respectively). The cumulative incidence of disease progression at 2 years was higher in patients with DEL (60% versus 13%; overall P = .005). The cumulative incidence of nonrelapse mortality did not differ statistically in the 2 groups. Even in patients with DEL and chemosensitive disease at transplantation, the 2-year progression-free survival rate was only 27% due to early disease progression. Multivariate analysis showed associations between DEL and increased risks of progression-free survival events (hazard ratio [HR], 4.58; 95% confidence interval [CI], 2.07-10.2; P <.001), overall mortality (HR, 2.29; 95% CI, 1.03-5.09; P = .042) and disease progression (HR, 3.60; 95% CI, 1.38-9.44; P = .009). Patients with DEL had poor outcomes after allogeneic transplantation. Innovative strategies are needed to improve outcomes in this population.

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Section: Discussioncontrasting

confidence: 80%

Double-Expressor Lymphoma Is Associated with Poor Outcomes after Allogeneic Hematopoietic Cell Transplantation

Kawashima¹,

Inamoto²,

Maeshima

et al. 2018

Biology of Blood and Marrow Transplantation

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“…By contrast, in 2 retrospective studies of allo-SCT for relapsed or refractory FL from Japan, using FM (Flu and Mel)-based or FB (Flu and Bu)-based RIC in a majority of cases, 49,50 the percentages of patients who had chemoresistant disease at allo-SCT were notably higher (63%-68%) than from other series from North America or Europe (Table 2). Nevertheless, the 5-year PFS and OS in those studies were 70%-84% and 77%-84%, respectively, with low NRM (16% for each study).…”

Section: Reduced-intensity Conditioning Allo-sctmentioning

confidence: 82%

Hematopoietic Stem Cell Transplantation for Follicular Lymphoma : Optimal Timing and Indication

Kim

2014

J Clin Exp Hematopathol

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The definitive management of advanced follicular lymphoma (FL) remains controversial due to various treatment options, including watchful waiting, single-agent or combination chemotherapy, monoclonal antibody, and radioimmunotherapy. These options can provide prolonged progression-free survival. However, they cannot cure advanced FL. Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the sole curative therapy for FL. Allo-SCT has had a major impact with the use of reduced-intensity conditioning regimens because of its lower associated nonrelapse mortality compared with myeloablative regimens. Autologous SCT (auto-SCT) shows high response rates and extends progression-free survival in patients with chemosensitive relapse. In the rituximab era, however, associated comorbidities, risk of secondary cancers, and presence of refractory disease have become problematic in the auto-SCT population. On the basis of results from large-scale randomized trials, upfront auto-SCT is not recommended. Novel conditioning regimens including radioimmunotherapy followed by either auto-SCT or allo-SCT are likely to show efficacy even in chemorefractory disease. Consequently, the optimal timing for SCT remains a matter of opinion, except for patients in first remission. However, the outcomes of allo-SCT and auto-SCT keep on improving. Physicians should note that there is no therapy with a track record equivalent to that of SCT for relapsed or refractory FL.

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“…8 In fact, in contrast to DLBCL, the relapse rate of grade 3b FL is in some series higher and survival is longer. 9,10,45 Moreover, several reports have found no difference in outcome between FL grades 3a and 3b when treated with anthracycline-based therapy, and molecular studies identified comparable gene expression profiles between FL grade 3a and FL grade 3b. [11][12][13][14] These findings, the advent of new-targeted therapies, and the clinical followup with limited sampling of the disease (ie, peripheral blood, fine needle aspiration biopsies) strictly demand new diagnostic tools able to differentiate such similar diseases.…”

Section: Discussionmentioning

confidence: 99%

The miR-17-92 microRNA cluster: a novel diagnostic tool in large B-cell malignancies

Fassina

Marino

Siri

et al. 2012

Laboratory Investigation

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Diffuse large B-cell lymphoma (DLBCL) can present as de novo or can arise through the transformation of many indolent lymphomas, including follicular lymphoma (FL). The morphological differentiation between germinal center-DLBCL (GC-DLBCL) and high-grade (grade 3) FL could be challenging; the accurate sub-classification of large B-cell lymphomas is mandatory in order to select the most appropriate among the new-targeted therapies. Recent expression profiling studies reported microRNAs (miRNAs) (and miR-17-92 cluster, in particular) as useful tools in differentiating DLBCL and FL. However, these preliminary results are based on cell line-derived data or did not consider grade 3 FL cases. To investigate this point, 36 cases of GC-DLBCL and 18 cases of grade 3 non-transforming FL were considered. All diagnoses were based on the World Health Organization criteria and were confirmed by clinical, histological, and immunohistochemical data. Six members of the miR-17-92 cluster (ie, miR-18b, miR-19b, miR-20a, miR-92, miR-93, and miR-106a) and two control miRNAs (ie, miR-150 and miR-210) were quantified by quantitative reverse transcription-polymerase chain reaction. All the considered miR-17-92 cluster miRNAs were significantly overexpressed in GC-DLBCL, being miR-20a and miR-106a the most dysregulated (Po0.001). Receiver operating characteristics (ROCs) analysis was used to find the optimal cut-off in distinguishing the two histotypes. The ROC estimated thresholds for miR-18b, miR-19b, miR-20a, miR-92, and miR-106a displayed a sensitivity level higher than 0.80 in achieving the GC-DLBCL diagnosis. The classification tree built on the six thresholds allowed the correct identification of 35/36 GC-DLBCL (97.2%). Profiling the miR-17-92 cluster is a promising investigative method for differentiating GC-DLBCL from high-grade FL. Subject to the validation of these findings in further larger studies; miR-17-92 cluster could represent a reliable, standardizable diagnostic tool for the sub-classification of large B-cell lymphoid neoplasm.

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Comparison of outcomes after allogeneic hematopoietic stem cell transplantation in patients with follicular lymphoma, diffuse large B‐cell lymphoma associated with follicular lymphoma, or de novo diffuse large B‐cell lymphoma

Cited by 13 publications

References 29 publications

Double-Expressor Lymphoma Is Associated with Poor Outcomes after Allogeneic Hematopoietic Cell Transplantation

Double-Expressor Lymphoma Is Associated with Poor Outcomes after Allogeneic Hematopoietic Cell Transplantation

Hematopoietic Stem Cell Transplantation for Follicular Lymphoma : Optimal Timing and Indication

The miR-17-92 microRNA cluster: a novel diagnostic tool in large B-cell malignancies

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