Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Grade Gliomas in Children and Adolescents

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.

Large indoor cage study of the suppression of stable Aedes aegypti populations by the release of thiotepa-sterilised males

The sterile insect technique (SIT) is a promising pest control method in terms of efficacy and environmental compatibility. In this study, we determined the efficacy of thiotepa-sterilised males in reducing the target Aedes aegypti populations. Treated male pupae were released weekly into large laboratory cages at a constant ratio of either 5:1 or 2:1 sterile-to-fertile males. A two-to-one release ratio reduced the hatch rate of eggs laid in the cage by approximately a third and reduced the adult catch rate by approximately a quarter, but a 5:1 release drove the population to elimination after 15 weeks of release. These results indicate that thiotepa exposure is an effective means of sterilising Ae. aegypti and males thus treated are able to reduce the reproductive capacity of a stable population under laboratory conditions. Further testing of the method in semi-field enclosures is required to evaluate the mating competitiveness of sterile males when exposed to natural environmental conditions. If proven effective, SIT using thiotepa-sterilised males may be incorporated into an integrated programme of vector control to combat dengue in Cuba.

Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Young Children with Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

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.

MUC1-positive circulating tumor cells and MUC1 protein predict chemotherapeutic efficacy in the treatment of metastatic breast cancer / 癌症

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.

Idiopathic hyperammonemia after chemotherapy with vinorelbine, topotecan, and cisplatin in a patient with acute lymphocytic leukemia

Idiopathic hyperammonemia [IHA] had been reported in some patients with hematological malignancy after receiving intensive chemotherapy, following bone marrow transplantation, or after using 5-fluorouracil for some solid tumors. The chemotherapeutic agents involved include cytarabine, daunomycin, cyclophosphamide, vincristine, amsacrine, etoposide, asparaginase, busulfan, and methotraxate, all used for treating hematological malignancies. No previous reports have described the association between idiopathic hyperammonemia and combined chemotherapy with vinorelbine, topotecan, and cisplatin. We describe a 20-year-old girl with normal liver function and relapsed precursor B-lymphoblastic leukemia receiving the modified TVTG [topotecan, vinorelbine, thiotepa, dexamethasone, and gemcitabine] protocol to control her disease. We used cisplatin [30 mg/m[2]/day] to replace thiotepa on day 3 because thiotepa was not available in Taiwan. The patient developed acute idiopathic hyperammonemia after 5 days of chemotherapy and died 9 days after chemotherapy. To our knowledge, this patient is the first report of the association of hyperammonemia and chemotherapy with vinorelbine, topotecan, and cisplatin in the English literature

[ comparison between intravesical chemotherapy and immunotherapy on superficial carcinoma of the bladder]

Intravesical chemotherapy or immunotherapy is the main point in treatment of superficial transitional cell carcinoma of bladder after performing TURBT[1]. But these methods have some limitations in terms of therapeutic response and the rate of complications. This study was performed to evaluate the complication rate, response to treatment and relapse of TCC[2]after mixed chemotherapy with Thiotepa and Mitomycine C in comparison with immunotherapy by BCG. In this clinical trial a total of 140 patients who admitted in urology department of Ghaem and Musa-Ebne-Jafar Hospital due to superficial TCC, were divided into 4 groups of 35. After TURBT, patients in first group were treated by Thiotepa, on second and third group we used monotherapy with Mitomycine C, BCG, respectively. So in the last group mixed therapy with Thiotepa plus Mitomycine C was performed. All patients in each group were followed by physical exam, lab tests [CBC, U/A] and cystoscopy every 3 months for the first 2 years, and then every 6 months until the end of study. CBC tests were performed before and after 8 weeks of every of therapy. Then gathering data was analyzed through statistical methods. In this study, maximum prevalence rate of TCC was in 7 and 8 decades with an average of 66 years old. In patients there was 3.5% T[Is], 43.5% stage T[a] and 53% stage T[1]. Tumors were mostly seen in the lateral walls and the base of bladder [94%]. In the group which treated with intravesical BCG, the recurrence rate of carcinoma was apparently lower than other groups and the remission's time was longer. The highest incidence rate of acute cystitis was seen in BCG-Therapy group, while in the mixed therapy group was lowest. Hematologic and allergic side-effects were significantly lower with mixed therapy in comparison with monotherapy methods. Rate of recurrence in BCG-therapy is lower but its complications, especially acute cystitis, is common. Administration of mixed therapy has been successful in reducing complications [both systemic and local]; but the therapeutic response was like the monotherapy treatment

Factors affecting hematologic recovery and infection in high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk solid tumor / 소아과

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(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.

High-Dose Chemotherapy of Cyclophosphamide, Thiotepa and Carboplatin (CTCb) followed by Autologous Stem-Cell Transplantation as a Consolidation for Breast Cancer Patients with 10 or more Positive Lymph Nodes: a 5-Year follow-Up Results / Journal of the Korean Cancer Association, 대한암학회지

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.

High-Dose Chemotherapy of Cyclophosphamide, Thiotepa, and Carboplatin (CTCb) Followed by Autologous Stem-Cell Transplantation for Metastatic Breast Cancer Patients: A 6-Year Follow-Up Result / Journal of the Korean Cancer Association, 대한암학회지

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.

High dose Chemotherapy and Autologous Stem Cell Transplantation for Poor Risk and Recurrent Non-Hodgkin's Lymphoma: A Single-Center Experience of 50 Patients

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.

High Dose Chemotherapy with Autologous Peripheral Blood Stem Cell Transplantation in Patients with Medulloblastoma/Primitive Neuroectodermal Tumor / 대한소아혈액종양학회지

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.

Busulfan, thiotepa, and melphalan as a conditioning regimen for allogeneic bone marrow transplantation in patients with acute myelogenous leukemia / 대한내과학회지

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.

A Case of Triple-Alkylating Regimen and Peripheral Blood Stem Cell Transplantation for a Patient with Relapsed Ovarian Carcinoma / 대한암학회지

Despite an aggressive surgical debulking followed by front-line chemotherapy, most patients with advanced ovarian carcinoma die of drug-resistant disease. Drug resistance can be overcome in a subset of patients with hematologic malignancies and lymphoma with high-dose therapy (HDT) and hematopoietic stem cell transplantation, suggesting that this therapy may also be value in ovarian carcinoma. We report the successful outcome of HDT and peripheral blood stem cell transplantation (PBSCT) in a 41-year-old nulliparous woman who initially was diagnosed with advanced ovarian carcicnoma with FIGO stage IIIc. Her disease relapsed after 19 months from initial therapy of definitive surgery and intra- and post-operative chemotherapy. Subsequently, she received optimal debulking surgery and salvage chemotherapy followed by HDT with triple- alkylating regimen, composed of cyclophosphamide (100 mg/kg), thiotepa (500 mg/m2), and melphalan (100 mg/m2). Her pretranplant characteristics were platinum-sensitive and complete response state. She showed rapid hematologic recovery and mild regimen-related toxicity (Bear man's toxicity criteria), stomatitis (grade I), cardiac toxicitiy (grade II). She has been followed up for 36 months after the inital therapy and is doing well without relapse.

A Preliminary Report of Allogeneic Stem Cell Transplantation for Patients with Acute Leukemia Conditioned by Triple-alkylating Regimen / 대한혈액학회지

BACKGROUND: We assessed the toxicity and feasibility of the three-alkylator combinations as conditioning regimens for allogeneic hemopoietic stem cell transplantation (HSCT) in 23 adult patients with acute leukemia. METHODS: Sixteen patients were transplanted for acute myeloid leukemia, six for acute lymphoblastic leukemia, and one for myelodysplastic syndrome. Group A included thirteen cases of relapsed refractory, 2 relapsed after first HSCT and group B eight patients in first complete remission or two in second complete remission. Eleven cases received G-CSF mobilized CD34+allogeneic peripheral blood stem cells (PBSCs) in addition to bone marrow (BM) and three in vivo expanded BM by G-CSF and eight unmanipulated BM and one from syngeneic BM after conditioned with busulfan, thiotepa and melphalan (n=14) or cyclophosphamide, thiotepa and melphalan (n=6) or TBI, melphalan and thiotepa (n=3). RESULTS: Twelve of thirteen patients in group A patients engrafted successfully and only one patient failed to achieve complete remission (CR). All patients in group B had successful engraftment. The median days reaching absolute neutrophil count (ANC) more than 500/microliter and platelet more than 30,000/microliter in group A and group B were 13.4 days (7-22), 17.9 days (9-40) and 16.3 days (10-21), 22.6 days (13-38), respectively. Acute graft vs host disease (GVHD) developed in both groups with the incidence of seven (78%) for group A and six (60%) for group B. The major regimen-related toxicity was mucositis with incidence of 95.7% (22/23). The disease free survival rate after HSCT with median follow-up of 161 days (31-283 days) and 101 days (22-163 days) in each group were 24% and 62.5%, respectively. CONCLUSION: Although the observation period is limited, this study shows that the combination of triple-alkylating regimens are tolerable as a preparative regimen for allogeneic HSCT for both high-risk and standard-risk leukemic patients. We need to confirm effects of these regimens in prospective randomized-controlled studies in the future. (allo-BMSCT) and 14 cases of autologous peripheral blood stem cell transplantation (aPBSCT) were underwent. With a median follow-up of 293 days (range, 35~510), the relapse rate was 34.1% (14/41 cases) in chemotherapy-only group and 13.5% (5/37 cases) in transplant-group. The probability of disease-free survival (DFS) at 2 years of chemotherapy-only group, aPBSCT group, and allo-BMSCT group were 20.1%, 44.9%, and 90%, respectively. The relapse-probability at 2 years of three groups were 76.1%, 55.1% and 11.1% in order, respectively. Univariate analyses showed that age (P=0.0274) and augmentation with BHAC (p=0.0334) were significant factors for achieving CR.

High Dose Cyclophosphamide, Thiotepa, and Carboplatin followed by Autologous Peripheral Stem Cell Rescue in Patients with Responsive Metastatic or High - Risk Primary Breast Cancer / 대한암학회지

PURPOSE: Positive correlation between dosage of antineoplastic agents and tumor response is well demonstrated in advanced breast cancer. But severe bone marrow depression limit the clinical application of high dose chemotherapy. Autologous peripheral blood stem cell transplantation(PBSCT) after high dose chemotherapy(HDC) was introduced to promote rapid bone marrow recovery. This study was designed to establish the feasibility of combining high dose cyclophosphamide, thiotepa, and carboplatin chemotherapy followed by stem cell rescue in patients with responsive metastatic or high risk primary breast cancer. MATERIALS AND METHOD: Eligibility criteria included the presence of high risk primary breast cancer(10 or more involved axillary lymph node, n=4), recurrent disease after curative resection(n=6) or stage IV disease at the time of diagnosis(n=1). The responses of recurrent disease to initial chemotherapy were 4 complete responses and 1 partial responses. One recurrent case with solitary pulmonary metastasis underwent metastasectomy and got chemotherapy after operation. Colony stimulating factor was administered to mobilize stem cells from bone marrow to peripheral blood. The stem cell collection was performed 4~10 times(median 4) and the number of collected stem cell was 1.95~7.34x10(8)kg(median 4.87x10(8)/kg). High dose chemotherapy with CTCb (cyclophosphamide 1,500 mg/m2/day, thiotepa 125 mg/m2/day, carboplatin 200 mg/m2/ day) was performed from day -7 to day -4 and peripheral stem cell infusion was performed on day 0 as planned. RESULT: Eleven patients were enrolled in this study. Their median age was 39 years old. The median time for bone marrow recovery was 11 days for neutrophil(>500/mm2) and 28 days for platelet(>50,000/mm2). Packed red blood cell and platelet transfusion were performed in 11 patients. The group whose infused mononuclear cell count was less than 4.0 x 10(8)/kg(n=9) needed longer time for bone marrow recovery than those(n=2) who had more than 4.0 x 10(8)/kg( 20 vs 13 day, p < 0.05 ). For non-hematologic toxicity, none have experienced toxicity more than grade III. There were 2 recurrences of 4 cases with high risk breast cancer at the 22 th, and 25 th month but they are still alive at the 28 th, and 29 th month each. The other 2 cases are alive without recurrences at the 18 th, and 20 th months each. In the recurrent disease group, one case who showed partial response to initial chemotherapy recurred at the 4 th month and died at the 13 th month after PBSCT. The other 5 cases are alive without recurrence at the 1st, 3 rd, 3 rd, 5 th, and 31 th month each. One case with stage IV disease(bone metastasis) is alive without evidence of progression at the 3 rd month. CONCLUSION: High dose chemotherapy with PBSCT can be performed safely. Long term survival of patients with advanced breast cancer would be possible by PBSCT after HDC. Further clinical trials based on larger patient population is required to evaluate clinical efficacy of PBSCT after HDC in high risk and recurrent breast cancer.

High-Dose Chemotherapy of Cyclophosphamide, Thiotepa, and Carboplatin (CTCb) with Autologous Peripheral Blood Stem Cell Transplantation for High-Risk Primary Breast Cancer and Metastatic Breast Cancer / 대한내과학회지

OBJECTIVES: Recently high dose chemotherapy with autologous peripheral blood stem cell transplantation (APBSCT) has been investigated with the hope of maximizing tumor response and increasing survival. The purpose of this study is to evaluate the effect, feasibility, and toxicity of high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) with APBSCT in patients with metastatic or high risk primary breast cancer. METHODS: Four cases of high-risk primary breast cancer (with more than 10 involved axillary nodes) and three cases of metastatic disease in complete or partial response were enrolled. Peripheral blood stem cells were mobilized by G-CSF plus chemotherapy, and median number of collected mononuclear cells was 5.44 X 108/kg(range, 1.95-7.08 X 108/kg). High-dose chemotherapy of cyclophosphamide (1,500mg/m2/day), thiotepa (125mg/m2/day) and carboplatin (200mg/m2/day) was administered for 4 days and peripheral blood stem cells were reinfused to the patients 72 hours after the completion of chemotherapy. RESULTS: The median days of recovery for neutrophil (over 500/mm3) and for platelet (over 50,000/mm3) were 10 (range, 8 to 33) and 30 (range, 10 to 40). One patient suffered from seizure attack and grade 3 hepatotoxicity during high dose chemotherapy, There were no treatment-related death. Four patients with high-risk primary breast cancer remained disease-free at 2, 8, 12 and 19 months post-transplant. In one patient with bone metastasis, complete response was induced following APBSCT. All three patients with metastatic disease remained progression-free at 8, 18 and 19 months post-transplant. CONCLUSION: High-dose chemotherapy and autologous peripheral blood stem cell transplantation was feasible and would be a potentially effective treatment modality in high risk and metastatic breast cancer.

A Preliminary Report of Busulfan, Melphalan and Thiotepa or TBI-containing Bi-alkylator Chemotherapy as a Preparative Regimen for Allogeneic Bone Marrow Transplantation in Refractory or Relapsed Acute Leukemias / 대한암학회지

PURPOSE: We assessed the three-alkylator combination of busulfan, melphalan and thiotepa or TBI, melphalan and thiotepa conditioning for allogeneic stem cell transplantation in 7 adult patients with refractory or relapsed acute leukemias. MATERIALS AND METHODS: Six patients were transplanted for acute myeloid leukemia, one for acute lymphoblastic leukemia and included 5 of relapsed refractory, 2 of relapsed after first-BMT. All but 1 cases received G-CSF stimulated CD34+ allogeneic peripheral blood progenitor cells (PBPCs) in addition to stimulated allogeneic marrow. RESULTS: All patients except one engrafted (median time to ANC >0.5 10 (9)/L=11days, to platelets >30 X 10 (9)/L=14 days) successfully and complete remission was obtained in 6 patients. Grade I-II acute GVHD and controllable regimen-related toxicity especially oral mucositis (grade II-III) developed in all cases, but 2 patients including one second- allogeneic BMT patient expired early by transplant-related toxicity of hepatic or multiorgan failure along the course of sepsis. CONCLUSION: Although the observation period on these cases are limited, the data presented show that the combination of busulfan, melphalan and thiotepa is tolerable as a preparative regimen for allogeneic marrow transplantation in high-risk leukemic patients. We think that these encouraging results need to be confirmed in prospective studies in the future.

Periósteo autógeno no tratamento da necrose de esclera após exérese de pterígio e betaterapia / Autogenous periosteum in scleral necrosis treatment after pterygium graft and betatherapy

Os autores apresentam um estudo no qual se utiliza o periósteo autógeno como alternativa de enxerto para o tratamento cirúrgico de necrose de esclera e exposiçäo uveal em olhos submetidos a betaterapia após exérese de pterígio. A revisäo da literatura demonstrou que o periósteo autógeno ainda näo havia sido utilizada neste tipo de patologia. A técnica foi empregada em cinco pacientes. Houve boa integraçäo em todos os casos. Como complicaçäo relatam um caso de dellen corneano e um caso de reabsorçäo parcial tardia do enxerto. Ressaltam a necessidade de tratar a necrose escleral para evitar a ocorrência de infecçäo que, frequentemente leva esses olhos a dano funcional irreversível.

Estudo comparativo da açäo do tiotepa e da mitomicina C na reparaçäo do epitélio corneano, em coelhas / A comparative study of the effect of mitomycin C and thio-thepa on superficial epithelial corneal healing in rabbits

Este estudo compara, em coelhas, a influência dos agentes anti-proliferativos, mitocina C e tiotepa, na cicatrizaçäo de defeitos epiteliais corneanos. Com a utilizaçäo de um cilindro de plástico, foi possível manter por 5 minutos a área de defeito epitelial em contato com 1 ml de soluçäo de cloreto de sódio 0,9 por cento (olhos controles) ou com 1 ml de uma das soluçöes: mitomicina C 0,02 por cento, mitomicina C 0,04 por cento ou tiotepa 1:2000 (olhos tratados). Dentro das condiçöes desse estudo, conclui-se que a exposiçäo à soluçäo de tiotepa näo influencia a reparaçäo da lesäo, enquanto a soluçäo de mitomicina C a 0,02 por cento e a 0,04 por cento retardam significativamente a cicatrizaçäo da área desepitelizada