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.     

Favorable outcome of patients with relapsed or refractory Hodgkin's disease treated with high-dose chemotherapy and stem cell rescue at the time of maximal response to conventional salvage therapy (Dexa-BEAM)

Background: Disease status before high-dose chemotherapy with autologous bone marrow transplantation (ABMT) or peripheral blood stem cell transplantation (PBSCT) is an important predictor of transplantation-related toxicity and event-free survival (EFS) for patients with relapsed or refractory Hodgkin's disease (HD). We performed a phase II study in patients with relapsed or refractory HD to evaluate the feasibility of four cycles of Dexa-BEAM followed by high-dose chemotherapy with ABMT or PBSCT.Patients and methods: Twenty-six patients (median age 30, range 20–40 years) were treated with 2–4 courses of dexamethasone, carmustine, etoposide, cytarabine and melphalan (Dexa-BEAM) as salvage chemotherapy in order to attain maximal response. Patients achieving complete response (CR) or partial response (PR) received high-dose chemotherapy with ABMT or PBSCT. The conditioning regimen used was CVB (cyclophosphamide, carmustine, etoposide).Results: Eighteen patients responded to Dexa-BEAM, resulting in a response rate of 69%. At the time of transplant 16 patients were in CR two patients in PR. At present 14 patients transplanted are in continous CR (median follow-up 40 months, range 14–60 months). Two patients with PR after four courses of Dexa-BEAM relapsed and died three months posttransplantation. Two patients with CR at the time of transplant relapsed after nine and 13 months respectively. Eight patients had rapid progressive disease after 2–4 cycles of Dexa-BEAM. One patient with progressive disease died in gram-negative sepsis after four cycles of Dexa-BEAM. There was no transplantation-related death.Conclusion: These data suggests the use of high-dose chemotherapy followed by stem cell transplantation at the time of maximal response.     

Update on ocular graft-versus-host disease

Ocular graft-versus-host disease (oGVHD) occurs as a complication following hematopoietic stem cell transplantation and is associated with significant ocular morbidity resulting in a marked reduction in the quality of life. With no current consensus on treatment protocols, management becomes challenging as recurrent oGVHD often refractory to conventional treatment. Most authors now diagnose and grade the disease based on criteria provided by the National Institutes of Health Consensus Conference (NIH CC) or the International Chronic oGVHD (ICCGVHD) consensus group. This article will provide an insight into the diagnostic criteria of oGVHD, its classification, and clinical severity grading scales. The inflammatory process in oGVHD can involve the entire ocular surface including the eyelids, meibomian gland, corneal, conjunctiva, and lacrimal system. The varied clinical presentations and treatment strategies employed to manage them have been discussed in the present study. The recent advances in ocular surface imaging in oGVHD patients such as the use of meibography and in vivo confocal microscopy may help in early diagnosis and prognostication of the disease. Researching tear proteomics and identification of novel potential tear biomarkers in oGVHD patients is an exciting field as they may help in objectively diagnosing the disease and monitoring the response to treatment.     

亲代外周血造血干细胞移植成功治愈重型β-地中海贫血1例

目的　研究了亲代供者外周血造血干细胞移植治疗重型β-地中海贫血(简称地贫)的相关问题。方法　改进了预处理方案:采用生理反馈机制,即在预处理前进行了高频输注红细胞悬液,使Hb达13 0g/L以上,同时口服羟基脲抑制造血使术前地贫骨髓的富细胞性变成贫细胞性,使用抗胸腺细胞球蛋白(ATG)加强对宿主淋巴细胞的攻击力度,结合使用马利兰、氟达拉宾和环磷酰胺。预处理后输异基因外周血干细胞3次。三次输入MNC分别为3 5×10 9/kg ,4 8×10 8/kg及6 2×10 7/kg。结果　移植过程中出现Ⅱ°皮肤GVHD、出血性膀胱炎、霉菌感染等并发症,均得到有效控制。+ 16d(移植后为+ )外周血等位基因PCR -STR检测13位点证实10个不相同位点均转为供体型(供受者本身有三个位点相同) ,完全植入。并于移植后+ 70d复查证实仍为完全植入状态。目前患儿移植后已5月余,无cGVHD表现。已五个月未输血制品,白细胞正常,血小板维持在90G/L ,血红蛋白维持在110g/L。结论　亲代所供HLA一个亚型不相合的外周血造血干细胞移植治疗重症β-地中海贫血是简单、可行的     

Analyses of minimal residual disease based on Flt3 mutations in allogeneic peripheral blood stem cell transplantation

Purpose Activating Flt3 mutations are observed in about 30% of patients with acute myeloid leukaemia (AML) and individual Flt3 mutations are applicable for minimal residual disease (MRD) analyses.Methods We investigated the MRD status in four AML patients carrying different Flt3 mutations (three patients with Flt3 length mutations of the juxtamembrane domain, one patient carrying a mutation of the Flt3 tyrosine kinase domain, i.e. Flt3-TKD mutation) who underwent allogeneic peripheral blood stem cell transplantation (PBSCT). Residual leukaemia cells were retrospectively determined by real-time PCR at different time points.Results We can demonstrate a good correlation between the course of MRD status and clinical events in all four investigated patients.Conclusion These examples demonstrate the potential impact of Flt3 based MRD status not only after but also prior to allogeneic PBSCT.     

Immune recovery of lymphocyte subsets 6 years after autologous peripheral blood stem cell transplantation (PBSCT) for lymphoproliferative diseases. A comparison between NHL, HD and MM in group of 149 patients

To evaluate the normalization of lymphocyte subsets several years after autologous peripheral blood stem cell transplantation (aPBSCT) and to detect any differences based on the underlying lymphoproliferative diseases, we analyzed the immunological recovery of 149 patients with Non Hodgkin's Lymphoma (NHL), Hodgkin's Disease (HD), Multiple Myeloma (MM). Lymphocyte recovery was assessed before the transplant, on days 15, 30, 60, 90, 120 and on years 1, 2, 4, 6. Analysis of a total of 709 lymphocytes, including total lymphocyte count, CD3 + , CD4 + , CD8 + , CD4 + /CD8 + ratio, CD19 + , CD3 + HLA-DR + , CD16 + 56 + , was performed. The normalization of total lymphocyte counts was achieved between days 14 to 22 following PBSCT. CD3 + cells count showed a normalization after 2 years in the HD and NHL groups and after 4 years in MM group. CD4 + subset achieved normalization during the sixth year in the 3 groups. The CD8 + and CD19 + lymphocytes subsets achieved normal values in the 3 groups at day 60 and at day 120 respectively. CD16 + 56 + and CD3 + /HLA-DR + lymphocytes showed median values above the normal range starting from day 30. Immunological recovery was similar in all 3 groups. Moreover, the recovery of all subsets evaluated was similarly demonstrated within 6 years after aPBSCT.     

Secondary chronic myelogenous leukemia after autologous peripheral blood stem cell transplantation for Lymphoma

A 31-year-old woman was diagnosed with intestinal lymphoma (high-grade mucosa-associated lymphoid tissue lymphoma, stage IIE) in September 1996. Eleven courses of chemotherapy were administered, but the results were poor. She received autologous peripheral blood stem cell transplantation (PBSCT) in September 1997. Leukocytosis was noted, and chronic myelogenous leukemia was diagnosed 8 months after the PBSCT, progressing to blast phase 10 months later. We report this case because secondary chronic myelogenous leukemia after stem cell transplantation is rare.     

外周血CD34+造血干细胞加适量T细胞输注进行HLA半相合的异体移植

对1例Ph+染色体的急淋患儿进行母子间HLA半相合的异体外周血造血干细胞移植 ,为避免由于HLA不相合所产生的由T细胞介导的严重移植物抗宿主病(GVHD) ,采用了CD34+细胞正性分离去除淋巴细胞 ;同时为避免由于T细胞过度去除而引起宿主抗移植物反应(HVG)导致植入失败 ,在移植次日又加入部分T细胞 ,使病儿接受CD34 +细胞6×106/kg 和CD3 +细胞1.05×107/kg。结果 :随访1年来 ,红系、粒系和巨核系均恢复正常 ,临床上仅出现一过性的IIOaGVHD以及轻微的局限于口唇粘膜的cGVHD。STR位点DNA检验以及染色体检查 :移植后 +180天受体已从供体型嵌合体转为完全供体型 ,病儿获得植入成功。结果表明 ,常规剂量的CD34 +细胞移植加以适量CD3 +T细胞 ,可克服HLA部分不相配的难点 ,减轻GVHD ,同时也可避免由于过度的T细胞去除而出现的HVG。