1.
Post-Irradiation Hyperamylasemia Is a Prognostic Marker for Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in Pediatric Population: A Retrospective Single-Centre Cohort Analysis
Baldo, F., Simeone, R., Marcuzzi, A., Grasso, A. G., Vidimari, R., Ciriello, F., Zanon, D., Maestro, A., Barbi, E., Maximova, N.
Journal of clinical medicine. 2021;10(17)
Abstract
BACKGROUND Total body irradiation (TBI) is a mandatory step for patients with acute lymphoblastic leukemia (ALL), undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In the past, amylases have been reported to be a possible sign of TBI toxicity. We investigated the relationship between total amylases (TA) and transplant-related outcomes in pediatric recipients. METHODS We retrospectively analyzed the medical records of all the patients who underwent allogeneic HSCT between January 2000 and November 2019. The inclusion criteria were the following: recipient's age between 2 and 18, diagnosis of ALL, no previous transplantation, and use of TBI-based conditioning. The serum total amylase and pancreatic amylase were evaluated before, during, and after transplantation. Cytokines and chemokines assays were retrospectively performed. RESULTS 78 patients fulfilled the inclusion criteria. Fifty-seven patients were treated with fractionated TBI, and 21 with a single-dose regimen. The overall survival (OS) was 62.8%. Elevated values of TA were detected in 71 patients (91%). The TA were excellent in predicting the OS (AUC = 0.773; 95% CI = 0.66-0.86; p < 0.001). TA values below 374 U/L were correlated with a higher OS. The highest mean TA values (673 U/L) were associated with a high disease-progression mortality rate. The TA showed a high predictive performance for disease progression-related death (AUC = 0.865; 95% CI = 0.77-0.93; p < 0.0001). Elevated TA values were also connected with significantly higher levels of proinflammatory cytokines, such as TNF-a, IL-6, and RANTES (p < 0.001). CONCLUSIONS this study shows that TA is a valuable predictor of post-transplant OS and increased risk of leukemia relapse.
2.
CD34+ selection and the severity of oropharyngeal mucositis in total body irradiation-based allogeneic stem cell transplantation
Anand, A., Anandi, P., Jain, N. A., Lu, K., Dunavin, N., Hourigan, C. S., Le, R. Q., Chokshi, P. D., Ito, S., Stroncek, D. F., et al
Supportive Care in Cancer. 2016;24(2):815-22
Abstract
OBJECTIVE The purpose of the present study was to evaluate the impact of ex vivo T cell depleted (TCD) by CD34+ selection on the incidence and severity of oropharyngeal mucositis (OM) after myeloablative allogeneic stem cell transplant (allo-SCT) with total body irradiation (TBI) conditioning. This approach has the advantage of avoiding methotrexate for graft versus host disease (GVHD) prophylaxis. PATIENTS AND METHODS We analyzed the incidence and severity of OM in a cohort of 105 consecutive patients who underwent CD34+ selected (peripheral blood stem cells (PBSCs) from human leukocyte antigen (HLA)-identical siblings) allo-SCT with total body irradiation (TBI) conditioning. OM was graded by the World Health organization (WHO) and the Bearman regimen-related toxicity (RRT) scales. RESULTS The incidence of WHO grade 3-4 OM was 34.3 %. There were no cases of grade 3-4 OM by the RRT scale. Significant correlation was found between the severity of OM and the use of intravenous (IV) narcotic medications (r (2)=0.15, p=0.004), total parenteral nutrition (TPN; r (2)=0.68, p<0.001), and hospital length of stay (LOS) (r (2)=0.12, p=0.01). DISCUSSION TBI-induced OM can inflict significant morbidity in the early transplant period, and the incidence of WHO grade 3-4 OM can exceed 50 % when methotrexate is used for GVHD prophylaxis. In the CD34+ selected setting, methotrexate is avoided and the incidence of WHO grade 3-4 OM, use of TPN, and need for narcotic analgesia appear to be lower than historic evidence from standard T-replete allogeneic transplantation. CONCLUSION We conclude that toxicity from OM is tolerable in CD34+ selected allo-SCT and should be prospectively measured in randomized trials comparing CD34+ selection versus T-replete transplantation.
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High Incidence of Veno-Occlusive Disease With Myeloablative Chemotherapy Following Craniospinal Irradiation in Children With Newly Diagnosed High-Risk CNS Embryonal Tumors: A Report From the Children's Oncology Group (CCG-99702)
Nazemi, K. J., Shen, V., Finlay, J. L., Boyett, J., Kocak, M., Lafond, D., Gardner, S. L., Packer, R. J., Nicholson, H. S.
Pediatric Blood & Cancer. 2016;63(9):1563-70
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Abstract
BACKGROUND The outcomes with high-risk central nervous system (CNS) embryonal tumors remain relatively poor despite aggressive treatment. The purposes of this study using postirradiation myeloablative chemotherapy with autologous hematopoietic stem cell rescue (ASCR) were to document feasibility and describe toxicities of the regimen, establish the appropriate dose of thiotepa, and estimate the overall survival (OS) and event-free survival (EFS). PROCEDURE The Children's Cancer Group conducted this pilot study in children and adolescents with CNS embryonal tumors. The treatment consisted of induction chemotherapy to mobilize hematopoietic stem cells, chemoradiotherapy, and myeloablative consolidation chemotherapy with ASCR. RESULTS The study accrued 25 subjects in 40 months and was closed early due to toxicity, namely, veno-occlusive disease (VOD) of the liver, more recently termed sinusoidal obstructive syndrome (SOS). Of 24 eligible subjects, three of 11 (27%) receiving thiotepa Dose Level 1 (150 mg/m(2) /day x 3 days) and three of 12 (25%) receiving de-escalated Dose Level 0 (100 mg/m(2) /day x 3 days) experienced VOD/SOS. One additional subject experienced toxic death attributed to septic shock; postmortem examination revealed clinically undiagnosed VOD/SOS. The 2-year EFS and OS were 54 +/- 10% and 71 +/- 9%, respectively. The 5-year EFS and OS were 46 +/- 11% and 50 +/- 11%. CONCLUSIONS The treatment regimen was deemed to have an unacceptable rate of VOD/SOS. There was complete recovery in all six cases. The overall therapeutic strategy using a regimen less likely to cause VOD/SOS may merit further evaluation for the highest risk patients. Copyright © 2016 Wiley Periodicals, Inc.