High-dose chemotherapy and autologous stem cell rescue in children with pediatric malignancies: single center experience
Yulia V. Dinikina, Anna Y. Smirnova, Andrey S. Egorov, Svetlana I. Chernova, Yulia K. Toshina, Margarita B. Belogurova
Department of Chemotherapy for Oncohematological Diseases and SCT, V. Almazov National Medical Research Center; Department of Oncology, Pediatric Oncology and Radiotherapy, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia
Contact: Dr. Yulia V. Dinikina
Prognosis of high-risk pediatric malignant tumors remains not satisfactory today. To improve the outcome of these patients (pts) high-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) as consolidation therapy is used. Toxicity profile and survival benefits of it should be determined carefully. Our aim was to evaluate the feasibility, toxicity and tumor response of HDCT with ASCT in pts with high-risk pediatric malignancies.
Patients and methods
The retrospective review of 36 HDCT courses with ASCR in 27 patients (pts) summarizes our single-center experience from 2016 to 2019. The most frequent HDCT regimens were: Carbo/Eto, 10 cases; Thiotepa/Cyc, 8; Thiotepa/Carbo/Eto, 7; Bu(Treo)/Mel, in 6 patients. The CTCAE 5.0 criteria were used for the toxicity estimation.
Median age of pts was 3 years (range 0.1-18 years), males – 70.3%. Six pts received HDCT as second-line regimen for relapsed malignancies, 10 pts underwent tandem HDC. Tumors types included: 27 – malignant CNS tumors, 3 – neuroblastoma, 3 – Ewing sarcoma, 1 – Hodgkin’s lymphoma, 1 – Non-Hodgkin’s lymphoma, 1 – Wilms tumor. In 33 cases, peripheral blood stem cells (PBSC) were used, in 3, bone marrow was transplanted. Collecting of PBSC was efficaciously carried out in all cases with a single leukapheresis procedure in 88.8%, in other – with 2 rounds. Mean number of 9.9×106 CD34+ cells/kg (range 2.74-26.6) body weight was achieved. Twelve of 27 pts were transplanted while in CR. Common toxicities included myelosuppression (100%), grade II-III stomatitis (64.4%), diarrhea grade II-III (61.1%). Among infectious episodes, the most frequent were enterocolitis (55.5%), febrile neutropenia (36.1%), bloodstream infections (13.8%). 75% of infections were microbiologically identified, thus Gram-negative bacteria predominated (60%). CMV reactivation was diagnosed in 29.6% of pts, among them: DNAaemia in 62.6%, and CMV disease, in 37.5% of the cases. 75% of pts with CMV-reactivation received antiviral therapy with ganciclovir, two pts had effective treatment (12.5%) with CMVIg. The median time to neutrophil engraftment was 11 days (range, 8-17) and to platelet recovery, 13 days (range, 9 to 29). Graft failure occurred in 5.5% of pts, and autologous cells were reinfused as a rescue. There were no cases of transplant-related deaths. CR after HDC/ASCR was achieved in 16.6% of the pts. In post-transplant period, 58.3% of the pts received radiotherapy. Median follow-up time was 13 months (range, 2-36). The 1-year OS and PFS are 81.4% and 62.9% respectively.
Our experience confirms that treatment regimens of HDC/ASCR demonstrate a chance of prolonged survival and are relatively well tolerated. The main profile of adverse events comprised bacterial infections with predominantly Gram-negative strains. Future prospective trials are needed to compare outcomes in pts after HDCT/ASCR with those receiving standard therapy in specific high-risk patient population.
High-dose chemotherapy, children, autologous stem cell rescue, high-risk malignancies.