Child ; Cord Blood Stem Cell Transplantation ; Hematopoietic Stem Cell Transplantation ; Humans ; Primary Myelofibrosis/therapy* ; Thiotepa ; Transplantation Conditioning

With the aim to investigate the outcome of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) for high-grade gliomas (HGGs), we retrospectively reviewed the medical records of 30 patients with HGGs (16 glioblastomas, 7 anaplastic astrocytomas, and 7 other HGGs) between 2006 and 2015. Gross or near total resection was possible in 11 patients. Front-line treatment after surgery was radiotherapy (RT) in 14 patients and chemotherapy in the remaining 16 patients including 3 patients less than 3 years of age. Eight of 12 patients who remained progression free and 5 of the remaining 18 patients who experienced progression during induction treatment underwent the first HDCT/auto-SCT with carboplatin + thiotepa + etoposide (CTE) regimen and 11 of them proceeded to the second HDCT/auto-SCT with cyclophosphamide + melphalan (CyM) regimen. One patient died from hepatic veno-occlusive disease (VOD) during the second HDCT/auto-SCT; otherwise, toxicities were manageable. Four patients in complete response (CR) and 3 of 7 patients in partial response (PR) or second PR at the first HDCT/auto-SCT remained event free: however, 2 patients with progressive tumor experienced progression again. The probabilities of 3-year overall survival (OS) after the first HDCT/auto-SCT in 11 patients in CR, PR, or second PR was 58.2% ± 16.9%. Tumor status at the first HDCT/auto-SCT was the only significant factor for outcome after HDCT/auto-SCT. There was no difference in survival between glioblastoma and other HGGs. This study suggests that the outcome of HGGs in children and adolescents after HDCT/auto-SCT is encouraging if the patient could achieve CR or PR before HDCT/auto-SCT.
Adolescent* ; Astrocytoma ; Brain Neoplasms ; Carboplatin ; Child* ; Cyclophosphamide ; Drug Therapy* ; Etoposide ; Glioblastoma ; Glioma* ; Hepatic Veno-Occlusive Disease ; Humans ; Medical Records ; Melphalan ; Radiotherapy ; Retrospective Studies ; Stem Cell Transplantation* ; Stem Cells* ; Thiotepa

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

PURPOSE: The purpose of this study was to evaluate factors affecting hematologic recovery and infection in high-dose chemotherapy(HDCT) and autologous stem cell transplantation(ASCT) in patients with high-risk solid tumor. METHODS: From January 2004 to December 2005, 72 HDCTs and ASCTs were applied to children with high-risk solid tumor at Samsung Medical Center. Medical records of these 72 HDCTs and ASCTs were retrospectively analyzed. RESULTS: The single most powerful predictor of neutrophil and platelet recovery was the number of transplanted CD34+ cells. The duration of high fever was significantly longer in young patients, in patients treated with total body irradiation and/or thiotepa, and in patients transplanted with lower CD34+ cell dose(<2x10(6)/kg). However, the difference in the duration of high fever according to the number of CD34+ cells was not clinically significant. CONCLUSION: Findings in this study suggest that HDCT and ASCT with low CD34+ cell dose is clinically feasible despite delayed hematologic recovery, especially at a dose >1x10(6)/kg per transplantation. Therefore, it is important not to defer the appropriate time for HDCT for an additional collection of hematopoietic stem cells if the number of collected CD34+ cells is >1x10(6)/kg per transplantation.
Blood Platelets ; Child ; Drug Therapy* ; Fever ; Hematopoietic Stem Cells ; Humans ; Medical Records ; Neutrophils ; Retrospective Studies ; Stem Cell Transplantation* ; Stem Cells* ; Thiotepa ; Whole-Body Irradiation

PURPOSE: The benefit of high-dose chemotherapy (HDC) for metastatic breast cancer (MBC) is controversial. We evaluated the efficacy and safety of HDC with cyclophosphamide, thiotepa, and carboplatin (CTCb) followed by autologous stem-cell transplantation (ASCT) for MBC patients. MATERIALS AND METHODS: From September 1994 to December 1999, 23 MBC patients were enrolled. All the patients received 2 to 10 cycles of induction chemotherapy. Before transplantation, 12 patients were in complete response (CR), nine were in partial response (PR), and two had progressive disease (PD). The HDC regimen consisted of cyclophosphamide 1, 500 mg/m2/day, thiotepa 125 mg/m2/day and carboplatin 200 mg/m2/day intravenously for 4 consecutive days RESULTS: After ASCT, 13 patients (56%) had a CR, five (22%) had a PR, three (13%) had no change, while two (9%) showed a PD. Seventeen patients relapsed or progressed during the median follow-up of 78 months. The median progression-free survival (PFS) time was 11 months and the median overall survival (OS) time was 23 months. The 5-year PFS and OS rates were 22% and 25%, respectively. On the multivariate analyses, less than 4 involved lymph nodes was predictive of a better PFS and OS. CONCLUSION: HDC with CTCb for MBC has acceptable toxicity; however, this treatment does not show a survival benefit.
Breast Neoplasms* ; Breast* ; Carboplatin* ; Cyclophosphamide* ; Disease-Free Survival ; Drug Therapy* ; Follow-Up Studies* ; Humans ; Induction Chemotherapy ; Lymph Nodes ; Multivariate Analysis ; Thiotepa*

PURPOSE: The benefit of consolidation high-dose chemotherapy (HDC) for high-risk primary breast cancer is controversial. We evaluated the efficacy and safety of consolidation HDC with cyclophosphamide, thiotepa and carboplatin (CTCb) followed by autologous stem-cell transplantation (ASCT) in resected breast cancer patients with 10 or more positive lymph nodes. MATERIALS AND METHODS: Between December 1994 and April 2000, 22 patients were enrolled. All patients received 2 to 6 cycles of adjuvant chemotherapy after surgery for breast cancer. The HDC regimen consisted of cyclophosphamide 1, 500 mg/m2/day, thiotepa 125 mg/m2/day and carboplatin 200 mg/m2/day intravenous for 4 consecutive days. RESULTS: With a median follow-up of 58 months, 11 patients recurred and died. The median disease-free survival (DFS) and median overall survival (OS) were 49 and 69 months, respectively. The 5-year DFS and OS rates were 50% and 58%, respectively. The 12 patients with 10 to 18 involved nodes had better 5-year DFS (67%) and OS (75%) than 10 patients with more than 18 involved nodes (30% and 38%, respectively). The most common grade 3 or 4 nonhematologic toxicity was diarrhea, which occurred in 5 patients (23%). No treatment-related death was observed. CONCLUSION: Consolidation HDC with CTCb followed by ASCT for resected breast cancer with more than 10 positive nodes had an acceptable toxicity but does not show promising survival.
Breast Neoplasms* ; Breast* ; Carboplatin* ; Chemotherapy, Adjuvant ; Cyclophosphamide* ; Diarrhea ; Disease-Free Survival ; Drug Therapy* ; Follow-Up Studies* ; Humans ; Lymph Nodes* ; Peripheral Blood Stem Cell Transplantation ; Thiotepa*

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

PURPOSE: To improve survival and/or to avoid radiotherapy, high dose chemotherapy (HDCT) with autologous peripheral blood stem cell transplantation (PBSCT) was given to patients with recurrent or high risk medulloblastoma (MB)/primitive neuroectodermal tumor (PNET) as well as patients younger than 3 years of age. METHODS: Six patients (3 recurrent, 1 high risk, 2 younger than 3 years; 5 MBs and 1 PNET) received single or double HDCT and PBSCT with or without immunotherapy using interleukin-2. Chemotherapeutic regimen in the first HDCT included cyclophosphamide (1,500 mg/m2/ day for 4 days) and melphalan (60 mg/m2/day for 3 days). Chemotherapeutic regimen in the second HDCT included carboplatin (400 mg/m2/day for 3 days), thiotepa (250 mg/ m2/day for 3 days), and etoposide (200 mg/m2/day for 3 days). RESULTS: Nine HDCTs were applied in 6 patients. Three double HDCTs were rescued with peripheral blood stem cells collected during single round leukapheresis. Rapid hematologic recovery occurred in 4 patients. Engraft failure occurred in 1 patient and delayed granulocyte recovery and platelet engraft failure occurred in 1 patient. Three patients who had minimal disease before HDCT had event free survival for 7~18 months after HDCT. Tumor relapsed 8 and 12 months after single HDCT in 2 patients among 3 patients with recurrent MB/PNET. One patient with recurrent MB died due to engraft failure and sepsis. CONCLUSION: HDCT with autologous PBSCT is expected to improve survival of patients with poor prognosis MB/PNET including younger patients less than 3 years. Subsequent trials with larger number of patients and long-term follow-up are needed.
Blood Platelets ; Carboplatin ; Cyclophosphamide ; Disease-Free Survival ; Drug Therapy* ; Etoposide ; Follow-Up Studies ; Granulocytes ; Humans ; Immunotherapy ; Interleukin-2 ; Leukapheresis ; Medulloblastoma ; Melphalan ; Neural Plate* ; Neuroectodermal Tumors* ; Neuroectodermal Tumors, Primitive ; Peripheral Blood Stem Cell Transplantation* ; Prognosis ; Radiotherapy ; Sepsis ; Stem Cells ; Thiotepa

BACKGROUND: The purpose of this study was to evaluate the toxicity and efficacy of high-dose chemotherapy with busulfan, thiotepa and melphalan (BTM) as a myeloablative regimen in allogeneic bone marrow transplantation (allo-BMT) for patients with acute myelogenous leukemia (AML). METHODS: Twenty-seven patients with AML were enrolled; Sixteen patients had standard risk (SR) diseases (first complete remission (CR1) and de novo AML) and eleven patients had high risk (HR) diseases (second, or subsequent remission, secondary AML, relapsed, or refractory AML, CR marrow with persisting extramedullary manifestation (chloroma), or hypoplastic acute leukemia). The conditioning regimen included busulfan 4 mg/kg/day for a total dose of 12 mg/kg; thiotepa 250 mg/m2/day for a total dose of 500 mg/m2; and melphalan 50 mg/m2/day for a total dose of 100 mg/m2. Cyclosporine A and short-course methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. RESULTS: The median time to recovery a granulocyte count of 0.5 x 109/L was 14 days (range 10~25 days) and platelet transfusion independence was 30 days (range 12~49 days). The major regimen-related toxicities were gastrointestinal-related symptoms including oral mucositis, nausea, vomiting, and diarrhea. All patients experienced oral mucositis (> or = grade 1) and the patients with oral mucositis of equal and greater than grade 3 were 44% in SR and 45% in HR. The toxicities associated with lung, skin, heart and brain were minimal. Three (11%) patients had severe or fatal veno-occlusive disease (VOD). There were five treatment-related death (19%) (hepatic VOD with multiorgan failure (n=3), pneumonia and ARDS (n=2)) within the first 100 days after allo-BMT. There was not a significant difference between SR and HR group (p=0.167). The incidence of acute GVHD equal or greater than grade II was less than 10%. The actual survival at 2 year was 70.4%(95% confidence interval (CI), 54.7%~86.1%)(SR; 81.3% (95% CI; 63.4~99.1%) vs HR; 54.6% (95% CI; 28.7~80.4%), p=0.154). After a median follow-up of 630 days, 18 of 27 (67%, 355~1062 days) patients are alive without evidence of disease. Three of the 27 patients relapsed (SR; 0% vs HR; 55.6% (95% CI; 19.6~71.3%), p=0.004). CONCLUSION: The BTM regimen followed by allo-BMT is associated with acceptable toxicity and appears to have significant activity in patients with AML. It should be used with caution in patients with prior hepatopathy or refractory state who have an increased risk of severe VOD. Busulfan, thiotepa, and melphalan is an effective and alternative myeloablative regimen for patients with AML.
Bone Marrow Transplantation* ; Bone Marrow* ; Brain ; Busulfan* ; Cyclosporine ; Diarrhea ; Drug Therapy ; Follow-Up Studies ; Graft vs Host Disease ; Granulocytes ; Heart ; Humans ; Incidence ; Leukemia, Myeloid, Acute* ; Lung ; Melphalan* ; Methotrexate ; Nausea ; Platelet Transfusion ; Pneumonia ; Skin ; Stomatitis ; Thiotepa* ; Transplantation, Homologous ; Vomiting