OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: To explore and evaluate the efficacy and safety of a modified thiotepa-based conditioning regimen combined with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of primary central nervous system lymphoma (PCNSL). METHODS: In a retrospective, single center, single arm study, we collected data of 28 patients with PCNSL who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) at our center from March 2021 to December 2024. The clinical characteristics of the patients, the conditioning regimen details, treatment-related toxicities and adverse reactions, post-transplant disease remission status, and survival outcomes were analyzed. RESULTS: A total of 28 patients were included. Among them, 19 patients received ASCT as first-line consolidation therapy in complete response (CR) or partial response (PR) status, and 9 patients with relapsed/refractory disease underwent salvage ASCT. The median time to neutrophil engraftment was 9 days (range: 5-11 days), and the median time to platelet engraftment was 10 days (range: 6-13 days). All patients achieved CR at the initial efficacy evaluation post-ASCT. The main complications during the transplantation period were febrile neutropenia (26 cases) and grade 3 diarrhea (9 cases). No transplantation-related mortality occurred. Post-ASCT, 19 patients received maintenance therapy, which was demonstrated to be safe and effective. Three patients relapse, and one patient died. The median progression-free survival (PFS) and overall survival (OS) of patients were not reached. The estimated 1-year and 2-year cumulative PFS rates were 88.4% and 66.3%, respectively, while the 1-year and 2-year OS rates were both 94.1%. CONCLUSION The modified thiotepa-based conditioning regimen combined with ASCT is safe and effective for the treatment of PCNSL.
Humans ; Thiotepa/therapeutic use* ; Retrospective Studies ; Transplantation, Autologous ; Transplantation Conditioning/methods* ; Central Nervous System Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Adult ; Lymphoma/therapy* ; Treatment Outcome ; Aged

The feasibility and effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) were evaluated in children younger than 3 yr of age with atypical teratoid/rhabdoid tumors (ATRT). Tandem HDCT/autoSCT was administered following six cycles of induction chemotherapy. Radiotherapy (RT) was administered if the tumor relapsed or progressed, otherwise, it was administered after 3 yr of age. Tumors relapsed or progressed during induction chemotherapy in 5 of 9 patients enrolled; 3 of these 5 received tandem HDCT/autoSCT as a salvage treatment. One patient died from sepsis during induction chemotherapy. The remaining 3 patients proceeded to tandem HDCT/autoSCT; however, 2 of these patients showed tumor relapse/progression after tandem HDCT/autoSCT. All 7 relapses/progressions occurred at primary sites even in patients with leptomeningeal seeding. Toxicities during tandem HDCT/autoSCT were manageable. A total of 5 patients were alive with a median follow-up of 20 (range 16-70) months from diagnosis. Four of 5 patients who received RT after relapse/progression are alive. The probability of overall survival at 3 yr from diagnosis was 53.3% +/- 17.3%. Our tandem HDCT/autoSCT is feasible; however, early administration of RT prior to tandem HDCT/autoSCT should be considered to improve the outcome after tandem HDCT/autoSCT.
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carboplatin/administration & dosage ; Central Nervous System Neoplasms/drug therapy/radiotherapy/*therapy ; Child, Preschool ; Combined Modality Therapy ; Cyclophosphamide/administration & dosage ; Etoposide/administration & dosage ; Female ; Follow-Up Studies ; Humans ; Induction Chemotherapy ; Infant ; Male ; Prospective Studies ; Recurrence ; Rhabdoid Tumor/drug therapy/radiotherapy/*therapy ; Salvage Therapy ; *Stem Cell Transplantation ; Survival Rate ; Thiotepa/administration & dosage ; Transplantation, Autologous

Chemotherapy plays an important role in the treatment of metastatic breast cancer. It is important to monitor chemotherapeutic efficacy, to find a simple and efficient tool to guide treatment, and to predict the efficacy of treatment in a timely and accurate manner. This study aimed to detect mucin-1 (MUC1)-positive circulating tumor cells and MUC1 protein in the peripheral blood of patients with metastatic breast cancer and to investigate their relationship to chemotherapeutic efficacy. MUC1 mRNA was detected in the peripheral blood of 34 patients with newly diagnosed metastatic breast cancer by reverse transcription-polymerase chain reaction. The positive rates of MUC1 mRNA were 88.2% before chemotherapy and 70.6% after chemotherapy, without a significant difference (P=0.564); MUC1 mRNA expression before chemotherapy had no correlation with treatment effectiveness (P=0.281). The response rate of MUC1 mRNA-negative patients after first-cycle chemotherapy was significantly higher (P=0.009) and the progression-free survival (PFS) was clearly longer than those of MUC1 mRNA-positive patients (P=0.095). MUC1 protein in peripheral blood plasma was detected by an ELISA competitive inhibition assay. The patients with decreased MUC1 protein after chemotherapy had a significantly longer PFS than those with elevated MUC1 protein (P=0.044). These results indicate that the outcomes of MUC1 mRNA-negative patients after chemotherapy are better than those of MUC1 mRNA-positive patients. In addition, patients with decreased expression of MUC1 protein have a better PFS.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; drug therapy ; secondary ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Cell Line, Tumor ; Disease-Free Survival ; Female ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Middle Aged ; Mucin-1 ; blood ; genetics ; metabolism ; Neoplastic Cells, Circulating ; metabolism ; RNA, Messenger ; metabolism ; Receptors, Progesterone ; metabolism ; Taxoids ; administration & dosage ; Thiotepa ; administration & dosage

BACKGROUND: The long-term survival of patients with non-Hodgkin's lymphoma after conventional chemotherapy is about 35%, with the remaining 65% of patients tending to be refractory or experience relapse. As such, primary refractory patients responding to salvage chemotherapy, and sensitive relapsed patients and primary high- risk patients are recommended to receive high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplantation (PBSCT). We evaluated the role of HDC and autologous PBSCT in patients with primary refractory, primary high risk, and sensitive relapsed non-Hodgkin's lymphoma. METHODS: We performed a retrospective analysis of the data from 50 patients with non-Hodgkin's lymphoma who were treated with HDC and autologous PBSCT in the Catholic Hematopoietic Stem Cell Transplantation Center between 1997 and 2002. RESULTS: Of the 50 patients, the conditioning regimen was BEAM in 20, CMT (cyclophosphamide, melphalan and thiotepa) in 19, fludarabine- and total body irradiation (TBI) -based regimen in 8, and cyclophosphamide and TBI in 2. There were 3 (6%) deaths due to treatment-related toxicity within the first 50 days after transplantation. Twenty-five patients remain alive at a median follow-up duration of 40.5 months (range 9~61). Among the patients with partial response before transplantation, 76% showed further response after transplantation. In half of these responders, the disease state was changed into complete response (CR) after transplantation. 2-year overall survival was 52% and 2-year progression free survival was 36.8%. Median overall survival was 34 months (range 8~60), and median progression-free survival was 8 months (range 1~14). Median overall survival was 14 months (range 9~19) in the primary high-risk group (n=13), 7 months (range 4~10) in the resistance relapse group (n=5), and 6 months (range 0~14) in the primary refractory group (n=10). Overall survival in the sensitive relapse group (n=22) did not reach the median; the mean overall survival in this group was 33 months. The disease status before transplantation was the only significant prognostic factor in determining overall survival (p=0.032) and progression- free survival (p=0.001). CONCLUSION: HDC and autologous PBSCT appears to produce high response rate. Primary high-risk group and sensitive relapse group had good prognosis, while refractory and resistance relapse group had poor prognosis. And the pre-transplantation disease status was the only significant prognostic factor in multivariate analysis.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse effects/*therapeutic use ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration & dosage ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Non-Hodgkin/drug therapy/radiotherapy/surgery/*therapy ; Male ; Melphalan/administration & dosage ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy/radiotherapy/surgery/*therapy ; Retrospective Studies ; *Stem Cell Transplantation ; Survival Analysis ; Thiotepa/administration & dosage ; Transplantation Conditioning/methods ; Transplantation, Autologous ; Treatment Outcome ; Vidarabine/administration & dosage/analogs & derivatives ; *Whole-Body Irradiation