Stem Cell Transplantation and Vinblastine Monotherapy for Relapsed Pediatric Anaplastic Large Cell Lymphoma: Results of the International, Prospective ALCL-Relapse Trial

Abstract

PURPOSE To analyze the efficacy of a risk-stratified treatment of children with relapsed anaplastic large cell lymphoma (ALCL). The ALCL-Relapse trial (ClinicalTrials.gov identifier: NCT00317408 ) stratified patients according to the time of relapse and CD3 expression to prospectively test reinduction approaches combined with consolidation by allogeneic or autologous hematopoietic stem cell transplantation (SCT) and vinblastine monotherapy. PATIENTS AND METHODS Patients with progression during frontline therapy (very high risk) or a CD3-positive relapse (high risk) were scheduled for allogeneic SCT after reinduction chemotherapy. Patients with a CD3-negative relapse within 1 year after initial diagnosis or prior exposure to vinblastine (intermediate risk) received autologous SCT after carmustine-etoposide-cytarabine-melphalan. This arm was terminated prematurely, and subsequent patients received vinblastine monotherapy instead. Patients with a CD3-negative relapse > 1 year after initial diagnosis (low risk) received vinblastine monotherapy. RESULTS One hundred sixteen patients met the inclusion criteria; 105 evaluable patients with CNS-negative disease had a 5-year event-free survival (EFS) of 53% ± 5% and a 5-year overall survival (OS) of 78% ± 4%. Before termination of autologous SCT, EFS rates of patients in the very-high- (n = 17), high- (n = 26), intermediate- (n = 32), and low- (n = 21) risk groups were 41% ± 12%, 62% ± 10%, 44% ± 9%, and 81% ± 9%; the respective OS rates were 59% ± 12%, 73% ± 9%, 78% ± 7%, and 90% ± 6%. Analyzing only the patients in the intermediate-risk group consolidated per protocol by autologous SCT, EFS and OS of 23 patients were 30% ± 10% and 78% ± 9%, respectively. All 5 patients with intermediate risk receiving vinblastine monotherapy after the amendment experienced relapse again. CONCLUSION Shorter time to relapse was the strongest predictor of subsequent relapse. Allogeneic SCT offers a chance for cure in patients with high-risk ALCL relapse. For early relapsed ALCL autologous SCT was not effective. Vinblastine monotherapy achieved cure in patients with late relapse; however, it was not effective for early relapses.

Super-enhancer-based identification of a BATF3/IL-2R−module reveals vulnerabilities in anaplastic large cell lymphoma

“…Furthermore, breast implant-associated ALK − ALCL (BIA-ALCL) and primary cutaneous ALCL (pcALCL) are acknowledged as (provisional) entities 2 , in particular the latter with usually good prognosis 3 . Despite implementation of targeted treatment strategies such as CD30 antibody-drug conjugates (ADCs) into up-front treatment regimens 4 , the prognosis of some particular systemic ALCL subtypes is unsatisfactory 5 , and there is an unmet medical need for effective treatment options in the case of relapsed and refractory disease 6,7 .…”

High-dose polychemotherapy with autologous hematopoietic stem cell transplantation in children with non-Hodgkin lymphomas

“…По данным Центра международных исследований трансплантации крови и костного мозга, у детей ауто-ТГСК предпочтительнее использовать при В-зрелоклеточных лимфомах, в то время как при ЛЛ и, возможно, при АККЛ более обоснованным является применение алло-ТГСК [14,18]. Вероятно, при В-НХЛ у детей реакция «трансплантат против опухоли» либо отсутствует, либо достаточно слабая.…”

“…Горбачевой с 2008 по 2020 г. ауто-ТГСК проведена 31 ребенку с Р-Р НХЛ. Медиана возраста на момент трансплантации составила 14 (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) лет. У большинства пациентов в дебюте отмечали III или IV стадию заболевания (n = 30, 97%), при этом поражение центральной нервной системы зарегистрировано у 4 (13%), поражение костного мозга -у 2 (6%) больных.…”

“…Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, 31 children with R/R NHL underwent auto-HSCT from 2008 to 2020. The median age at the time of transplantation was 14 (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) years. At the onset of the disease, most patients were diagnosed with stage III or IV cancer (n = 30, 97%), the CNS involvement was registered in 4 patients (13%), the bone marrow involvement was registered in 2 patients (6%).…”

Hematopoietic Stem Cell Transplantation for Pediatric Lymphomas

“…A recent prospective trial conducted by the European group showed that late relapses could be treated with vinblastine as a single agent and that high risk disease had 65% 5-year EFS following allogeneic HSCT. The autologous transplantation arm, initially planned for patients in the intermediate risk group (CD3 negative with relapse < 1 year and who had already received vinblastine) was held after inferior outcomes results were described when compared to the allogeneic HSCT group (EFS 44% ±9%), suggesting that early relapse disease should be consolidated with allogeneic transplantation 24 .…”