Collection of peripheral blood stem cells with granulocyte-colony-stimulating factor alone in testicular cancer patients.

BACKGROUND: High-dose chemotherapy with the transplantation of peripheral blood stem cells (PBSC) has been performed for the treatment of advanced testicular cancer patients. Recently, it has been reported that, in healthy donors, a large quantity of stem cells can be transferred to peripheral blood using granulocyte-colony-stimulating factor (G-CSF) alone. Therefore, it was decided to try to harvest PBSC from three patients having testicular cancers with G-CSF alone. METHODS: The three patients with testicular cancer were 26, 56 and 62-years-old. They had undergone five, two and three cycles of chemotherapy, respectively, but no radiation therapy. Granulocyte colony-stimulating factor was subcutaneously injected (250 microg) into each patient twice per day for 6 days. Peripheral blood stem cells were harvested for 3 days (days 4-6) and mononuclear cells (MNC), CD34-positive cells and colony-forming units of granulocyte-macrophage (CFU-GM) in PBSC collected by apheresis were measured. RESULTS: Apheresis showed that the total MNC count was 20.2 x 10(8)/kg (range, 10.6-25.9 x 10(8)/kg), the CD34-positive cell count was 0.98 x 10(6)/kg (range, 0.75-1.4 x 10(6)/kg) and the total CFU-GM count was 1.36 x 10(5)/kg (range, 0.25-3.0 x 10(5)/kg). CONCLUSION: After mobilization of peripheral blood stem cells with G-CSF alone, sufficient amounts of MNC were obtained from testicular cancer patients who had undergone chemotherapy several times. However, sufficient amounts of CD34-positive cells and CFU-GM could not be obtained. These results suggested that the G-CSF dose was not adequate for harvesting sufficient amounts of CD34-positive cells and CFU-GM.     

Peripheral blood stem cell harvest for patients with germ cell tumors

From January 1996 to December 1999, fifteen patients with germ cell tumors underwent peripheral blood stem cell harvest during 15 courses of bleomycin, etoposide, cisplatin (BEP), 4 courses of etoposide, ifosfamide, cisplatin (VIP) and 3 courses of high-dose etoposide mobilization at Nagoya University Hospital. We performed 29 aphereses during BEP, eight during VIP, and six during high-dose etoposide. Although we were able to harvest 4.4 x 10(6)/kg of median CD34 positive cells per apheresis during BEP, the number of stem cells (more than 4 x 10(6)/kg of CD34 positive cells), which are needed for tandem high-dose chemotherapy, could not be obtained during four courses of BEP. For three patients in whom white blood cell counts at nadir were 2,000/microL or more, however, the required number of CD34 positive cells were harvested. VIP provided only 1.7 x 10(6)/kg of median CD34 positive cells per apheresis, while, 7.3 x 10(6)/kg of CD34 positive cells were harvested during high-dose etoposide mobilization. The dose of G-CSF was a significant factor for the number of CD34 positive cells harvested during BEP (p = 0.02); however, there might be some relationship between the harvest and the number of the peripheral white blood cells on the day of apheresis (p = 0.08), the day to start G-CSF (p = 0.13), or the day to initiate apheresis (p = 0.27). Based on our experience, it is recommended that 5 micrograms/kg of G-CSF should be started from the 14th or 15th day of BEP until the last apheresis and that aphereses should be performed between the 19th and 21st day, especially at the days when the peripheral white blood cell count increases beyond 10,000/microL.     

High-dose chemotherapy followed by peripheral blood stem cell transplantation in advanced extragonadal germ cell tumor--a case report]

We reported the experience of high-dose chemotherapy (HDC) combined with peripheral stem cell transplantation (PBSCT) in 29 years-old man with advanced retroperitoneal germ cell tumor accompanied with left supraclavicular lymph node metastases, who obtained complete remission after comprehensive treatment. The initial levels of serum AFP, hCG and beta-hCG were high at 30.2 ng/ml, 14,000 mIU/ml and 66 ng/ml, respectively. After 3 courses of chemotherapy (BEP regimen), while left supraclavicular lymph node swelling was disappeared, the retroperitoneal mass lesion persisted on CT scan. Not all of 3 markers fell to the normal range. After myelosuppressive chemotherapy (etoposide 500 mg/m2 Day 1-3), PBSCs were collected by two consecutive apheresises on Day 17 and 18. In total, 19.5 x 10(6)/kg CD 34 positive cells were obtained. The patient underwent PBSCT (all CD 34 positive cells were infused) on Day 0 following HDC (CBDCA 250 mg/m2/day, etoposide 300 mg/m2/day, IFM 1.5 g/m2/day, Day-7(-)-3, respectively). He became severely leukopenic and thrombopenic with nadir of 200/microliter on Day 6 and 2 x 10(4)/microliter on Day 2, respectively. By administration of platelet transfusion and G-CSF, the white blood cell counts and thrombocyte counts recovered to 6,400/microliter and 4.1 x 10(4)/microliter on Day 10, respectively. Microbiologically enterocolic and respiratory tract infections occurred with elevated body temperature (> 40 degrees C). Antibiotic and antimycotic treatments were continued until disappearance of all clinical and microbiological evidence. He was kept for 10 days in clean room. After HDC, all markers fell to the normal range, but the retroperitoneal residual mass still persisted. Resection of the residual mass and retroperitoneal lymph node dissection were performed with pathological examination revealing tissue necrosis without viable cell. The patient has survived with no sign of the disease for 9 months.     

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.     

Transient increase in mitogen-induced lymphoproliferative responses in patients with testicular cancer after BEP chemotherapy

OBJECTIVES: To investigate the impact of polychemotherapy on cellular immunity in patients with testicular cancer. METHODS: Lymphocyte subpopulations, lymphoproliferative responses to mitogenic stimulation, and mitogen-induced release of soluble interleukin-2 receptor from peripheral blood mononuclear cells were investigated in 15 patients with testicular germ cell tumors a median of 61 months (range 7 to 73) after polychemotherapy with bleomycin, etoposide, and cisplatin (BEP). RESULTS: The numbers of peripheral blood T cells (CD3+), CD4+ and CD8+ subsets, and lymphoproliferative responses to pokeweed mitogen, phytohemagglutinin, and concanavalin A in patients were comparable to those of healthy control subjects. When two groups of patients were formed according to elapsed time from BEP polychemotherapy and study onset (group A, 12 months and group B, 69 months after termination of BEP), a significant increase in lymphoproliferative response to concanavalin A (P <0.05) was found in group A 1 year after chemotherapy. CONCLUSIONS: BEP chemotherapy administered to patients with testicular cancer does not result in impairment of cellular immunity but rather leads to a significant increase in the capacity of patients' lymphocytes to respond to mitogenic stimulation up to 1 year after polychemotherapy. Moreover, the increased T-cell activity found after BEP therapy may contribute to the high rate of long-term complete remission.     

High-dose chemotherapy with peripheral blood stem cell autotransplantation for patients with poor-risk testicular germ cell tumors--pilot study of the Japan Blood Cell Transplantation Study Group

The efficacy and toxicity of a single cycle of high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) in patients with poor-risk testicular germ cell tumors (GCT) enrolled in the Japan Blood Cell Transplantation Study Group was investigated. Previously untreated poor-risk testicular GCT patients were treated with BEP therapy (cisplatin, etoposide and bleomycin) with or without high-dose chemotherapy (carboplatin, etoposide and ifosphamide) followed by PBSCT. Patients were qualified for a change to high-dose chemotherapy if elevated serum tumor markers (human chorionic gonadotropin-beta, alpha-fetoprotein and lactate dehydrogenase) was observed after 3 cycles of BEP therapy. Eighteen patients were treated with BEP therapy alone and 16 with BEP and high-dose chemotherapy. At the completion of high-dose chemotherapy, all tumor markers had returned to normal in 6 patients. Among them, 1 had only teratoma found at resection and 5 had carcinoma resected. Nine patients who had persistent elevation of any tumor marker were treated with high-dose chemotherapy or another anticancer drug. Thirteen are alive (81%) and 9 (56%) are continuously disease-free at a median follow up of 11 months. The median time from PBSCT to a granulocyte count > 500/microL was 9.5 days and to a platelet count > 50,000/microL was 13 days.     

Second mobilization of peripheral blood progenitor cells in patients with poor first mobilization

The aim of this study was to analyse the efficacy of 2 second mobilization (MB) protocols in 2 groups of patients who failed to obtain enough peripheral blood progenitor cells (PBPC) in the first MB. In 1 group (8 patients), 10 microg/kg of G-CSF was administered, and in the other group (8 patients), a double dosage (10 microg/kg twice a day) was administered. Both groups of patients received Cyclophosphamide (1.5 g/kg) 10 days before the apheresis. No difference was found among both groups of patients in diagnosis, previous chemotherapy, and time elapsed after the first MB. Administration of higher doses of G-CSF decreased the number of apheresis needed in the second MB to complete 2 x 10(6)/kg of CD34+ cells. It also increased the number of patients who achieved sufficient CD34+, namely, 75% versus 50%.     

Mobilization and Collection of Peripheral Blood Stem Cells: Guidelines for Blood Volume to Process, Based on CD34-Positive Blood Cell Count in Adults and Children

We report 189 mobilizations and 489 collections of peripheral blood stem cells (PBSC) performed in 139 autologous transplantation patients and in 28 donors for allogeneic transplantations whose ages ranged from 2-68 years. We observed a correlation (P < .001; Pearson's coefficient 0.64) between CD34-positive cells and granulocyte-macrophage colony-forming units examined to estimate PBSC. In a subset of 287 collections (97 adults and 49 children) we obtained peripheral blood (PB) CD34-positive cell counts at 2 to 4 hours before leukapheresis. We noted a correlation between PB CD34-positive cell counts before leukapheresis and the number of CD34-positive cells per kilogram of body weight collected in the whole apheresis of the day (P < .001; Pearson's coefficient 0.82). An even better correlation was obtained between PB CD34-positive cells preapheresis and the yield of each individual blood volume (BV) processed (P < .001; Pearson's coefficient 0.87). Healthy donors and patients in each age group behaved similarly. In addition, the collection yield was greater among children than adults. These findings allowed us to develop a simple predictive model to estimate the BV to process for a target dose of CD34-positive cells per kilogram, based on the level of PBSC before apheresis in children and adults.     

Changes in cellular immunity during chemotherapy for testicular cancer

BACKGROUND: The changes in vivo in immunocyte functions during chemotherapy that is administered in combination with granulocyte colony-stimulating factor (G-CSF) in humans have not been fully investigated. This study was designed to examine neutrophil functions and the activities of natural killer (NK) cells, during the administration of chemotherapy and G-CSF for the treatment of testicular cancer. METHODS: Seven patients with germ cell tumors at stage IIA, IIB or IIIB, who were treated with bleomycin, etoposide and cisplatin (BEP), were enrolled in the study. Numbers and activities of neutrophils and NK cells were measured at various times during and after the first course of chemotherapy. Neutrophil phagocytosis was quantitated by flow cytometry with fluorescent latex beads. Bactericidal activity was measured in terms of colony-forming units. The activity of NK cells was measured by monitoring the release of 51Cr. RESULTS: After BEP chemotherapy, CD16+ and CD56+ cell counts, and neutrophil granulocyte counts decreased while there were no significant changes in the number of lymphocytes. Phagocytosis by neutrophils was enhanced after administration of G-CSF. The activity of NK cells was severely impaired after chemotherapy and did not change after administration of G-CSF. CONCLUSIONS: After BEP chemotherapy for testicular cancer with G-CSF, neutrophil function was not at all inferior to those before treatment. Natural killer cell activity was suppressed by the BEP chemotherapy and did not change after administration of G-CSF.     

Keimzelltumoren – ein Update

Recently a rise in the incidence of testicular germ cell cancer (TGCC) has been repeatedly reported in Germany (18% during the period 2000–2006). Future investigations are needed to examine causes for this increase in TGCT. The mortality rates in the western and eastern parts of Germany converge, but there is still a significantly higher mortality rate in the eastern part. Again future investigations are needed to examine causes for this phenomenon. In cases of testicular microlithiasis, testicular biopsies should be considered if further factors representing testicular dysgenesis syndrome are present, such as infertility, atrophic testes, and undescended testes. One course of adjuvant BEP reduces the risk of relapse by approximately 90% and may be a new option as the initial treatment for all CS1 NSGCT. Patients obtaining a CR (<1 cm) after first-line chemotherapy can be safely observed without PC-RPLND. Relapses are rare and potentially curable with further treatment.     

Clinical results of super high-dose chemotherapy with peripheral blood stem cell transplantation for patients with advanced germ cell tumor

We examined the clinical results of super high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) in 14 patients with poor-risk advanced germ cell tumors. The mean number of nadir white blood cells was 205 +/- 126/microliter; the mean period of number of white blood cells fewer than 1,000/microliter was at 8-10 days (mean +/- SD; 9.2 +/- 0.92). The nadir number of blood platelet cells was 1.7 +/- 0.70 x 10(4)/microliter; the mean period of number of platelet cells fewer than 5 x 10(4)/microliter was at 12.6 +/- 2.17 days. Of 10 patients treated with super high-dose chemotherapy with PBSCT as induction therapy, 8 patients (80%) showed that the serum tumor marker returned within the normal range after super high-dose chemotherapy. Of 8 patients, 7 underwent resection of the residual tumor. Surgical or pathological CR was obtained in 5 of these 7 patients, 4 patients of whom were alive with no evidence of disease 29 to 49 months after initial consultation: the other patient died with recurrence 20 months after initial visit. On the other hand, super high-dose chemotherapy with PBSCT was performed for one patient as consolidation, and for 3 patients with recurrence. Of these 4 patients, one died from disease 6 months after detection of recurrence. The other 3 patients were alive with no evidence of disease at 7-37 months after initial visit. The 1- and 3-year disease-free survival rates were 88% and 72%, respectively. In conclusion, super high-dose chemotherapy with PBSCT can be done safely and could be useful for patients with poor-risk germ cell tumor.     

Higher dose of CD34+ peripheral blood stem cells is associated with better survival after haploidentical stem cell transplantation in pediatric patients

Haploidentical stem cell transplantation (SCT) is increasingly used to treat pediatric patients with malignant or nonmalignant hematological disorders. The CD34+ dose of bone marrow or peripheral blood stem cells (PBSCs) has been shown to be an important determinant of the transplant outcome in adults under various preparative regimens. However, knowledge of the effect of the CD34+ dose in pediatric haploidentical SCT is limited. We analyzed the data of 348 pediatric patients (aged 2‐18 years) with acute or chronic leukemia, myelodysplastic syndrome (MDS), and other hematological disorders that received a transplant between 2002 and 2012. The results of multivariate analysis showed that PBSC CD34+ counts greater than 1.01 × 10⁶ kg^?1 improved platelet engraftment, improved overall survival, and reduced nonrelapse mortality. In contrast, a higher PBSC CD34+ dose did not affect the incidence of acute or chronic graft‐versus‐host disease, including engraftment syndrome. These data suggest that a PBSC CD34+ dose greater than 1.01 × 10⁶ kg^?1 is optimal for pediatric haploidentical SCT.     

Reversibility of the effects of subchronic exposure to the cancer chemotherapeutics bleomycin, etoposide, and cisplatin on spermatogenesis, fertility, and progeny outcome in the male rat

Testicular cancer is the most common cancer among young men of reproductive age. A regimen of bleomycin, etoposide, and cisplatin (BEP regimen) is the standard chemotherapy for testicular cancer. BEP has adverse effects on spermatogenic function that pose a long-term reproductive health risk to cancer survivors and their progeny. Using a rat model, we investigated the persistence of the effects of BEP on male reproductive function, fertility, and progeny outcome. Adult male Sprague-Dawley rats received a BEP regimen mimicking human clinical exposure (three 21-day cycles of etoposide and cisplatin on days 1-5 and bleomycin on days 2, 9, and 16, or vehicle). Reproductive and progeny outcome parameters were assessed at the end of BEP treatment and up to 9 weeks post-treatment, at 3-week intervals. BEP treatment reduced testicular weights and impaired spermatogenesis, characterized by abnormal testis histology and germ cell depletion. Germ cell apoptosis increased at least 3-fold in BEP-treated rats compared with controls at the end of treatment; 9 weeks posttreatment, germ cell apoptosis in BEP-treated rats did not differ from controls. BEP-exposed males were fertile; a decrease in litter size and an increase in preimplantation and postimplantation losses were observed. Preimplantation loss remained elevated in litters sired by BEP-treated males up to 9 weeks posttreatment; however, neither postimplantation loss nor litter sizes differed from controls. Thus, both germ cell apoptosis and the postimplantation loss induced by BEP treatment were reversible. The persistence of the elevation in preimplantation loss 9 weeks after BEP treatment suggests that spermatogonia are affected.     

Cotreatment with darbepoetin and granulocyte colony-stimulating factor is efficient to recruit proangiogenic cell populations in patients with acute myocardial infarction

To determine whether newer combination cytokine treatment with granulocyte colony-stimulating factor (G-CSF) and darbepoetin can improve efficacy of stem cell therapy, we evaluated safety and peripheral blood stem/progenitor cell (PBSC) mobilizing effects of combination cytokine in comparison with G-CSF alone in patients with acute myocardial infarction (AMI). We randomized 60 patients with AMI into two groups under 2:1 ratio; combination treatment with darbepoetin and G-CSF (n = 41: Combicytokine group) and the G-CSF alone (n = 19: G-CSF group). After coronary angioplasty, G-CSF was treated for 3 days with dose of 10 μg/kg/day in both groups. Only in the combicytokine group, additional single intravenous injection of 4.5 μg/kg of darbepoetin was administrated immediate after coronary angioplasty. Combination cytokine treatment was well tolerated as was G-CSF alone. PBSCs were obtained by apheresis for intracoronary infusion after completion of cytokine treatment and were analyzed by flow cytometry. The purity of proangiogenic cells was higher in combination cytokine group than the G-CSF group. Specifically, proportion of CD34(+)/KDR(+) endothelial progenitor cells, CD3(+)/CD31(+) angiogenic T cells and Tie2(+)/CXCR4(+) cells in apheresis products were higher in the combicytokine group. These meant that the combicytokine treatment recruited PBSCs in higher purity and fewer unwanted inflammatory cells than G-CSF alone in apheresis products. Combination treatment with darbepoetin and G-CSF is safe and more efficient to mobilize and recruit proangiogenic cells than G-CSF alone in patients with AMI. (Trial registration: www.ClinicalTrials. gov identifier: NCT00501917).     

Isolation of endothelial cells and their progenitor cells from human peripheral blood

Purpose: We have developed techniques to isolate endothelial cell (EC) progenitors from human peripheral and umbilical cord blood. Methods: Human adult peripheral and umbilical cord blood monocytes were isolated by centrifugation, and progenitor cells were separated with the use of magnetic polystyrene beads that were coated with a monoclonal antibody specific for the CD34 cell–membrane antigen. Cells were propagated in selective media, and developing cultures were immunostained for CD31, CD34, factor VIII, and vascular endothelial growth factor cell receptors. ECs that developed were transfected with a gene for prourokinase and used to line ePTFE grafts, which were evaluated in vitro in a pulsatile flow system. Results: Umbilical cord monocyte cultures demonstrated colonies that resembled ECs at approximately 2 weeks, with growth being best supported by EC growth media plus 20% calf serum with iron. Immunostaining of colonies was positive for CD31 and factor VIII. After 18 days in culture, CD34⁺ cells from adult peripheral blood were noted, which had the typical cobblestone appearance of ECs and immunostained positively for CD31 and factor VIII–related antigens. Cultures of umbilical cord–derived cells and adult peripheral blood–derived cells developed complex line formations within 1 week in culture that stained positively for vascular endothelial growth factor receptor-2. Urokinase-transfected ECs were shown to overexpress urokinase. Prosthetic grafts lined with transfected cells showed 87.33% ± 4.97% cell adherence after 2 hours in a pulsatile flow system at clinically relevant shear stress. Conclusion: We conclude that endothelial progenitor cells can be isolated from human adult peripheral and umbilical cord blood and developed into EC cultures as a source of cells for vascular graft seeding and gene therapy. (J Vasc Surg 2000;31:181-9.)     

Cytokine-mobilized peripheral blood progenitor cells for allogeneic reconstitution of miniature swine

BACKGROUND: Because of the relative ease of acquisition, increased yield, and improved engraftment characteristics, mobilized peripheral blood progenitor (stem) cells (PBSCs) have recently become the preferred source for hematopoietic stem cell transplantation. In our laboratory, procurement of a megadose of PBSCs is necessary for on-going studies evaluating non-myelosuppressive transplant regimens for the induction of mixed chimerism and allograft tolerance. To exploit hematopoietic growth factor synergy, we have sought to combine growth factors with proven utility to improve PBSC mobilization and maximize our PBSC procurement through an automated collection procedure. METHODS: Mobilization characteristics of PBSCs were determined in 2-5-month-old miniature swine. Animals received either swine recombinant stem cell factor (pSCF, 100 microg/kg) and swine recombinant interleukin 3 (pIL-3, 100 microg/kg), administered intramuscularly for 8 days, or pSCF, pIL-3, and human recombinant granulocyte-colony stimulating factor (hG-CSF), at 10 microg/kg. Leukapheresis was performed beginning on day 5 of cytokine treatment and continued daily for 3 days. RESULTS: Collection of PBSCs from cytokine-mobilized animals via an automated leukapheresis procedure demonstrated a 10-fold increase in the number of total nucleated cells (TNC) (20-30 x 10(10) TNC) compared to bone marrow harvesting (2-3 x 10(10) total TNC). A more rapid rise in white blood cells (WBCs) was seen after administration of all three cytokines compared to pSCF and pIL-3 alone. An increase in colony-forming unit granulocyte-macrophage frequency measured daily from peripheral blood during cytokine treatment, was seen with the addition of hG-CSF to pSCF/pIL-3 correlating well with the rise in WBCs. Similarly, the addition of hG-CSF demonstrated a notable increase in the median progenitor cell yield from the 3-day leukapheresis procedure. Cytokine-mobilized PBSCs were capable of hematopoietic reconstitution. PBSCs mobilized with pSCF/pIL-3 were infused into an SLA-matched recipient conditioned with cyclophosphamide (50 mg/kg) and total body irradiation 1150 cGy. Neutrophil and platelet engraftment occurred on days 5 and 7, respectively, with minimal evidence of graft-versus-host disease. Complete donor chimerism has been demonstrated 331 days after transplant. CONCLUSIONS: Our preliminary results show that in this well-defined miniature swine model, recombinant swine cytokine combinations (pSCF, pIL-3 with or without hG-CSF) successfully mobilize a high yield of progenitor cells for allogeneic transplantation. Furthermore, these cytokine-mobilized PBSCs demonstrate the potential to reconstitute hematopoiesis and provide long-term engraftment in miniature swine.     

Secondary leukemia following ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer

Secondary leukemia following chemotherapy or radiotherapy for mediastinal germ cell tumors in a well-described entity. It also may occur in patients with testicular germ cell tumors. We report a case of secondary leukemia occurring in a 31-year-old man who received ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) for a refractory testicular cancer (pathology; Seminoma, Embryonal carcinoma, Yolk sac tumor, Choriocarcinoma) with IIIB2 under Japanese classification, poor-risk group under Indiana classification. The initial levels of serum LDH, AFP and beta-HCG were high at 959 IU/l, 1,452 ng/ml and 800 ng/ml. He received total 11 cycles of systemic chemotherapy (2 cycles of PVB regimen, 4 cycles of PEB regimen, 3 cycles of VIP regimen and 2 cycles of ultra high-dose chemotherapy with PBSCT for pulmonary and para-aortic lymph node metastasis following his initial orchiectomy. The total amount of etoposide (VP-16), cisplatin (CDDP), carboplatin (CBDCA) and ifosfamide (IFM), this patient received was 7,225 mg/m2, 1,510 mg/m2 1,750 mg/m2, and 50.5 g. He has survived with CR of disease. Severe and persistent pancytopenia developed 25 months after his initial orchiectomy. Bone marrow examination showed AML (M2 with eosinophilia) under French-America-British (FAB) classification. Therefore, he was diagnosed as secondary leukemia following high-dose chemotherapy. He received total 6 cycles of systematic chemotherapy for the secondary leukemia in the internal department. He is planing to have bone marrow transplantation. To our knowledge, this is the first reported case in the literature relevant to secondary leukemia following ultra high-dose chemotherapy with PBSCT in testicular tumor in Japan.     

Clinical study for management of supportive treatment for high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) for intractable testicular tumor

The side effects of high-dose anti-cancer drug chemotherapy with peripheral blood stem cell transplantation (PBCST) for the treatment of intractable testicular tumor are very serious. In particular, agranulocytosis in bone marrow suppression may be life threatening. In this study, we examined opportunistic infectious diseases and preventive counter measures in the compromised conditions of anti-cancer drug chemotherapy. The patients underwent anti-cancer drug chemotherapy with PBCST for the treatment of intractable testicular tumors at Kobe University Hospital from September 1996 to September 2002. The high-dose chemotherapy regimen consisted of total doses per course of 1,250 mg/m2 carboplatin, 1,500 mg/m2 etoposide, and 7,500 mg/m2 ifosfamide. Twenty-four men (median age, 30 years; range, 18-70 years) received 50 courses of chemotherapy in total. The nadir of peripheral leukocyte counts was less than 1,000/mm3 in all courses, and the mean period was for 7.1 days. None of these patients developed critical sepsis leading to disseminated intravascular coagulation or treatment-related death. Our detailed data show that we can perform high-dose anti-cancer drug chemotherapy with PBSCT for intractable testicular tumors without serious infectious complications if we take sufficient preventive countermeasures for infectious diseases.     

One cycle of bleomycin, etoposide and cisplatin plus two cycles of etopeside and cisplatin chemotherapy in selected patients with low-volume stage II nonseminomatous germ cell tumor of the testis

OBJECTIVE: To assess the feasibility of bleomycin omission from second and third cycles of bleomycin, etoposide and cisplatin (BEP) chemotherapy in low-volume stage II nonseminomatous germ cell tumor patients who achieve a normal tumor marker level after the first cycle of treatment. MATERIALS AND METHODS: Out of 59 nonseminomatous testicular cancer patients with low-volume retroperitoneal disease, serum markers normalized after the first cycle of treatment in 30 cases. 12 patients completed 3BEP (group 1; years 1994-1998) and other 18 patients received etoposide and cisplatin (EP) as second and third cycles of chemotherapy (group 2; years 1998-2004). RESULTS: All patients from each group achieved complete response with chemotherapy alone or by subsequent resection of teratoma or necrosis. There was no relapse with active cancer after the treatment. All patients remained disease-free during the median follow-up period of 97 and 48 months for groups 1 and 2 respectively. CONCLUSIONS: One cycle of BEP plus two cycles of EP chemotherapy was as effective as three standard cycles of BEP. The regimen can be suggested as a less toxic therapeutic alternative in these selected patients. More cases, however, in a prospective randomized setting are required to further verify these data.