Two-step ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer: a case report]

A 35-year-old male had advanced nonseminomatous germ cell tumor (stage IIIC, embryonal cell carcinoma) which proved refractory to conventional PVB combined chemotherapy. He was then treated with an ultra high-dose chemotherapy consisting of carboplatin (1.5 g/m2) and etoposide (1.3 g/m2), followed by the transplantation of peripheral blood stem cells (PBSCT) with a total of 1.9 x 10(5)/kg granulocyte colony-forming cells (CFU-GM). Because he developed lung metastasis, escalated doses of carboplatin (2.0 g/m2), and etoposide (1.8 g/m2) combined with cyclophosphamide (7.0 g/m2) were given with peripheral blood stem cell transplant of 3.2 x 10(5)/kg CFU-GM. He has remained free of any recurrence without maintenance therapy.     

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

Between June 1998 and August 2000, five patients with germ cell tumor were treated with high-dose CEI: carboplatin (1,250 mg/m2), etoposide (1,500 mg/m2), and ifosfamide (7.5 g/m2), followed by peripheral blood stem cell transplantation (PBSCT) at Yokohama City University Hospital. All patients were classified into either poor risk group of International Germ Cell Consensus Classification or advanced extent of Indiana University stage, and received one cycle of high-dose CEI after 4-6 cycles of standard PEB (cisplatin, bleomycin, vinblastin) therapy. Three of the patients achieved complete response, one achieved partial response and one achieved no change after whole treatment. There were no fatal complications and no treatment-related deaths.     

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

BACKGROUND: The present study was performed in order to investigate the efficacy and safety of high-dose chemotherapy for the treatment of patients with advanced testicular cancer. METHODS: Seven patients were treated with high-dose carboplatin, etoposide and cyclophosphamide followed by peripheral blood stem cell transplantation. Five patients received one cycle and two patients received two cycles of the high-dose chemotherapy. RESULTS: Of the seven patients, one achieved a complete response and four achieved partial responses with markers negative. As a result of subsequent surgery for residual tumors, three of the four partial responders showed no residual cancer cells. One patient who did not undergo surgery received radiotherapy after the high-dose chemotherapy and the residual tumors disappeared. All five patients who had either a complete or partial response are still alive and without evidence of disease at 12, 27, 30, 37 and 40 months. One patient is alive with disease at 7 months and one died of progressive disease at 6 months. The hematologic recovery after high-dose chemotherapy was rapid and non-hematologic toxicities were usually mild and manageable. CONCLUSIONS: High-dose chemotherapy followed by peripheral blood stem cell transplantation is safe and effective for use in patients with far-advanced testicular cancer, particularly when the high-dose chemotherapy is conducted as the initial treatment. Further larger and long-term follow-up studies are needed to define the role of high-dose chemotherapy on testicular cancer.     

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

BACKGROUND: The aim of this study was to investigate the efficacy and safety of high-dose chemotherapy (HDCT) for the treatment of patients with advanced testicular cancer. METHODS: Fourteen patients were treated with high-dose carboplatin, etoposide and cyclophosphamide (with or without THP-adriamycin) followed by peripheral blood stem cell transplantation. The treatment was used for two refractory cases, a second relapse, and for consolidation after the first relapse in one case each. It was also used for nine cases as part of the first-line treatment following primary conventional-dose chemotherapy, and for one case as the first salvage for a late recurrent tumor of teratoma with malignant transformation. RESULTS: The first two patients who received intensive pretreatment with cisplatin-based chemotherapy did not respond to HDCT. The two patients who were treated with HDCT as the first or second salvage therapy achieved successful outcomes. The results for the subsequent nine patients (consisting of two with stage IIIC, five with IIIB2, one with IIB, and one extragonadal seminoma) were two progressive disease, three no change and four partial remission. Only three are alive with NED following salvage surgery. Finally, a case of teratoma with malignant transformation did not respond well to two cycles of HDCT. There were no marked adverse reactions except one episode of severe neutropenic colitis. CONCLUSIONS: The results demonstrated the limited efficacy of HDCT even in cases with a good to intermediate risk rating according to classification by the International Germ Cell Cancer Collaborative Group. Because treatment for relapse after HDCT is extremely difficult, new HDCT regimens consisting of drugs that are not used in induction chemotherapy need to be established.     

Renal complications of high-dose chemotherapy and peripheral blood stem cell transplantation

Following bone marrow transplantation, acute renal failure and proteinuria are common complications with a high mortality, particularly in patients requiring hemodialysis. Incidence, potential predisposing factors, and outcome of acute renal complications in patients with hematological malignancies receiving autologous peripheral blood stem cell transplantation were prospectively studied in 53 patients. Eight patients developed acute renal failure. Three of them required hemodialysis. Of all patients with acute renal failure, only those requiring hemodialysis died, due to nonrenal causes. Only 1 of the 45 patients without renal failure died. Mild proteinuria of predominantly tubular origin occurred in 16 patients, in 3 with and in 13 without acute renal failure. As predisposing factors for acute renal failure were identified: renal hypoperfusion due to systemic inflammatory response syndrome, sepsis or septic shock, and combined administration of nephrotoxic drugs. Especially those patients receiving high numbers of nephrotoxic drugs in combination with renal hypoperfusion were likely to develop acute renal failure. These results suggest that patients receiving high-dose chemotherapy and autologous peripheral blood stem cell transplantation have a low risk of developing acute renal failure and proteinuria.     

Clinical study of high-dose chemotherapy with peripheral blood stem cell transplantation for poor-risk germ cell tumor

Between January 1997 and December 1998, six patients with germ cell tumor were treated with high-dose CEC: carboplatin (1,500 mg/m2), etoposide (1,200 mg/m2) and cyclophosphamide (100 mg/kg), followed by peripheral blood stem cell transplantation (PBSCT) at Nagoya University Hospital. Four patients received one cycle of high-dose CEC and two received two cycles. The reasons why the high-dose CEC was administered included: 1) refractory to the induction chemotherapy (AFP/beta-HCG elevated during the induction chemotherapy or prolonged half-life of each marker) in three patients, 2) relapse in two patients, and 3) consolidation in one with unresectable mediastinal residual tumor. There were no treatment-related deaths and grade 1 hepatotoxicity occurred in one (17%) patient. The median duration (range) from PBSCT until a granulocyte count of 500/microL and a platelet count of 50,000/microL was 8.5 (8-11) and 11 (9-16) days, respectively. Of the six patients studied, 5 responded to the treatment; two achieved a complete response (CR) and three achieved a partial response (PR). One patient achieving a CR and two achieving a PR remained in complete remission after 23 to 24 months of follow-up, while the remaining patients with a CR, a PR and an incomplete response died of the disease. High-dose CEC could be administered without serious toxicity but the effectiveness of high-dose CEC for the poor-risk patients with germ cell tumor needs to be further investigated.     

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.     

自体外周血干细胞移植支持下的大剂量化疗在乳腺癌术前治疗中的应用

目的：观察自体外周血干细胞移植支持下的大剂量化疗（HDC／APBSCT）在乳腺癌术前治疗中应用的可行性。方法：本组3例乳腺癌患者,分别为T3N1M0（Ⅲa期）、T4N1M0（Ⅲb期）、T4N1M1（Ⅳ期）,均给予HDC／APBSCT治疗后,再予以手术。HDC／APBSCT实行过程为：FEC方案诱导化疗2个周期,给后评定疗效;自体外周血干细胞动员、采集、冻存;大剂量化疗及APBSC回输支持治疗。3例患者采用的治疗为：环磷酰胺2．5g/m^2、足叶乙甙600mg/m^2和卡铂600mg/m^2。HDC／APBSCT治疗后重新评定疗效,选择手术方案并实施。例1行乳腺癌根治术、例2行改良根治术,例3行改良根治加大面积植皮术。结果：HDC／APBSCT治疗后4周（例1、例2）以及33d后（例3）给予手术治疗。经观察对手术操作无明显影响,伤口愈合良好,其中例3同时给予一期大面积植皮亦愈合良好。Ⅲa、Ⅲb期2例患者随访时间已起过30个月至今健康生活。Ⅳ期患者术后16个月死于脑部转移。结论：HDC／APBSCT在乳腺癌术前治疗中具有一定可行性。将该方法做为中晚期乳腺癌患者的一种可供选择的抢救性治疗措施是值得偿试的。     

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.     

First-line high-dose chemotherapy combined with peripheral blood stem cell transplantation for patients with advanced extragonadal germ cell tumors

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of first-line high-dose chemotherapy (HDCT) combined with peripheral blood stem cell transplantation (PBSCT) for patients with advanced extragonadal germ cell tumors (EGGCT). METHODS: Six male patients with advanced non-seminomatous EGGCT were treated with HDCT combined with PBSCT following 2-3 cycles of conventional-dose induction chemotherapy. The regimens used for HDCT were carboplatin, etoposide and ifosfamide (ICE) in five patients and ICE plus paclitaxel (T-ICE) in one patient, and that for induction therapy was cisplatin, etoposide and bleomycin (PEB) in all patients. As a rule, HDCT was continuously administered until alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin normalized (beta-HCG). RESULTS: Following 1-6 courses of HDCT (median, 4 courses), beta-HCG and AFP were normalized in all patients, and five and one patient were diagnosed as showing partial remission and stable disease, respectively. Five patients underwent surgical resection of residual tumors after HDCT, yielding necrotic tissue in two, mature teratoma in two, and viable cancer tissue in one, and the surgical margin was negative in all patients. At a median follow-up of 36 months, five patients were alive and disease-free, whereas the remaining one died of disease progression. Although all patients had grade 3 hematological toxicity, there was no treatment-related death by combining PBSCT. CONCLUSIONS: First-line HDCT with PBSCT could be safely administered to patients with advanced EGGCT, and the antitumor effect of this treatment was comparatively favorable. First-line HDCT therefore may represent an attractive option for patients with advanced EGGCT.     

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.     

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.     

Gynecomastia following chemotherapy for testicular cancer

A 22-year-old man received 4 cycles of bleomycin, etoposide and cisplatin combination chemotherapy for clinical stage IIA embryonal cell carcinoma of the right testis. The treatment resulted in complete remission. Five months following cessation of the chemotherapy first on the left and then 2 weeks later on the right side painful gynecomastia developed. His hormonal values are all normal with no evidence of recurrence of the cancer. Gynecomastia on both sides resolved in 8 months spontaneously without any treatment. He is still in clinical remission 14 months after completion of the chemotherapy. We should be aware that gynecomastia following cytotoxic chemotherapy in a young man does not necessarily mean the return of the cancer.     

The salvage chemotherapy for refractory testicular cancer with novel anticancer agents

Despite the generally high cure rate in patients with metastatic testicular cancer, 20% to 30% of treated patients will become candidates for salvage chemotherapy. We reviewed the recent salvage chemotherapy trials of refractory diseases. CPT-11 is a new derivative of camptothecin and has activity in a variety of solid tumors. We evaluated the antitumor effect of combination chemotherapy using CDDP and CPT-11 against refractory testicular cancer. Fourteen patients who failed to achieve complete remission with salvage chemotherapy were treated with combination chemotherapy with CPT-11 and CDDP or 254-S (nedaplatin) as third line chemotherapy. Six patients remain alive and disease-free and 5 patients died of disease. The combination of CPT-11 and either CDDP or nedaplatin was significantly more effective than other salvage therapy regimens such as VIP. Paclitaxel, ifosfamide, etoposide regimens were also effective in patients with refractory testicular tumors. We concluded that these combination regimens demonstrated significant activity against refractory testicular tumor and further investigation is warranted.     

A case of Sweet''s syndrome following septic pulmonary emboli after high-dose chemotherapy for advanced testicular cancer

A 33-year-old man with advanced testicular cancer underwent high-dose chemotherapy combined with peripheral blood stem cell transplantation. After administration of granulocyte colony-stimulating factor (G-CSF), multiple infiltrative erythema was identified on the face, thigh, and lower leg. A dermatologist diagnosed this as Sweet's syndrome caused by G-CSF; consequently G-CSF administration was stopped. When the skin lesions had improved, phlebitis was found at the injection site of the peripheral vein catheter. The patient then suffered from sudden left chest pain and dyspnea. Chest computed tomography showed the characteristic findings of septic pulmonary emboli (SPE). He was treated by the administration of vancomycin, fluconazole, and pazufloxacin mesilate. Although Sweet's syndrome and SPE are rare diseases, the presence of these diseases must be considered when performing chemotherapy for urological malignancy.     

Kinetics of peripheral blood CD34-positive cells and the optimum timing for harvesting peripheral blood stem cells during BEP chemotherapy in patients with testicular germ cell tumor

PURPOSE: Recently, high-dose chemotherapy with peripheral blood stem cell (PBSC) rescue has been developed for poor risk testicular germ cell cancer. In this study, we investigated the optimum timing for harvesting PBSCs with the use of bleomycin + etoposide + cisplatin (BEP) chemotherapy, which is a well known first-line regimen for the testicular cancer. MATERIAL AND METHOD: Peripheral blood CD34-positive cell ratios were measured during a total of 10 courses of BEP chemotherapy in 6 patients with metastatic germ cell cancer between 1996 and 1998. We performed 4 apheresis in 3 patients during this period. Recombinant human granulocyte-colony stimulating factor (rhG-CSF) was administrated from the day on which the neutrophil count decreased less than 1,000/microliter. RESULTS: The peripheral blood CD34-positive cell ratios became maximum (3.0-24.6%; average 10.0%) on the day 18 to 21 (median day 19) of BEP chemotherapy with rhG-CSF administration. The maximum ratios of peripheral blood CD34 positive cells were achieved when the number of leukocyte were 6,880-23,600/microliter and exceeded 6,000/microliter after the 18th day of BEP chemotherapy. The average number of collected CD34 positive cells was 9.5 x 10(6)/kg at a single apheresis, and 12.6 x 10(6)/kg per patient. CONCLUSION: Efficient hematopoietic progenitor cells were mobilized by BEP chemotherapy with rhG-CSF administration of first-line setting. Our results suggest that the optimum timing of PBSCs harvest is the day when the numbers of leukocyte exceed 6,000/microliter after the 18th day of BEP chemotherapy and the following day.     

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.     

Orchidectomy after chemotherapy for patients with metastatic testicular germ cell cancer

OBJECTIVE: To evaluate the contribution of routine orchidectomy in the management of patients who present with advanced, metastatic, testicular germ cell cancer and who are treated with initial chemotherapy. PATIENTS AND METHODS: Sixty consecutive patients presenting with metastatic testicular germ cell cancer and treated with initial chemotherapy followed by orchidectomy were identified. The results from a clinical and pathological review of these patients are presented. The pathological findings at orchidectomy were compared with the pathological findings from metastatic masses resected after chemotherapy, and are reviewed with the clinical outcome. RESULTS: Of the 60 orchidectomy specimens after chemotherapy, 24 (40%) contained significant histological abnormalities comprising residual invasive germ cell cancer, intratubular germ cell neoplasia and/or mature teratoma. The remaining 36 (60%) orchidectomy specimens contained fibrous scarring with or with no necrosis. Six (10%) orchidectomy specimens contained residual invasive germ cell cancer, three nonseminomatous germ cell cancer (NSGCT) and three seminoma. The patients with residual invasive NSGCT present within the testis had evidence of residual invasive NSGCT within extragonadal masses resected after chemotherapy; all three have relapsed and died from chemorefractory progressive disease. CONCLUSION: Orchidectomy after chemotherapy is recommended in all patients undergoing primary chemotherapy, as a significant proportion (40%) are left with histological abnormalities that predispose to subsequent relapse. Persistence of invasive NSGCT at the site of the primary tumour after chemotherapy is associated with persistence of invasive disease at other metastatic sites and is a poor prognostic finding.     

A case of therapy-related leukemia/myelodysplastic syndrome following treatment of refractory testicular germ cell tumor

We report a patient with a refractory testicular non-seminomatous germ cell tumor (NSGCT) who developed therapy-related leukemia (TRL) after undergoing salvage chemotherapy and multiple operations for repeat recurrences. Fifty months after the initial therapy, pancytopenia and myeloblasts were observed in the patient's peripheral blood while the patient was undergoing salvage chemotherapy for a fifth recurrence. A bone marrow examination showed evidence of myelodysplastic syndrome (MDS) and refractory anemia with excess of blasts in transformation (RAEB in T) under French-America-British (FAB) classification. Cytogenetic 5q-/7q- abnormalities were also observed. The patient had received a total dose of 189g/m2 of Ifosfamide, 8,250mg/m2 of Etoposide and 1,450 mg/m2 of Cisplatin; therefore, he was diagnosed as having TRL/MDS. The patient has received induction chemotherapy for TRL with Cytarabine, Daunorubicin and Fludarabine while a bone marrow transplantation has been scheduled. Recently, TRL associated with chemotherapy are being reported with increasing frequency in the literature. Since early detection and treatment are necessary for the management of TRL, peripheral blood examinations should be performed after a diagnosis of refractory germ cell tumor has been made. If pancytopenia is detected, bone marrow and cytogenetic examinations should be immediately performed to rule out TRL.