High-dose chemotherapy with autologous peripheral blood stem cell transplantation for treatment of non-Hodgkin's lymphoma

Findings for 41 patients with non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy (HDC) and/or autologous peripheral blood stem cell transplantation (PBSCT) are reported. Two of the 41 patients were treated with HDC alone without PBSCT. At transplant, 20 patients were in complete remission, while 19 had resistant NHL and had failed to achieve a complete remission (CR) after several courses of conventional chemotherapy. The conditioning regimens used were mainly ACE (cytarabine, cyclophosphamide, etoposide) and MEAC (MCNU, etoposide, cytarabine, cyclophosphamide). The treatment-related mortality rate was 4.9%. Two patients treated with MEAC died from intractable congestive heart failure. Nine of the 19 patients with resistant NHL achieved CR, and at a median follow-up of 26 months (range, 3 to 93 months) the estimated two-year disease-free survival rate for these patients was 44.4%. Four patients in CR at present were in partial remission before HDC and PBSCT. Fifteen of the 20 patients in CR before HDC were transplanted in first CR and 5 in 2nd CR. At a median follow-up of 49 months (range, 3 to 96 months), the estimated 3-year DFS for the group of all patients was 73.7%. Five relapses occurred between 5 and 35 months post-transplantation. In conclusion, HDC and PBSCT as induction therapy was only effective for patients with resistant NHL who responded to conventional chemotherapy, and may improve the survival of patients in CR as consolidation therapy.     

High-dose chemotherapy with autologous stem cell rescue in breast cancer

SummaryBackground Because metastatic breast cancer is a lethal disease despite some responsiveness to systemic chemotherapy, high-dose chemotherapy with autologous stem cell rescue is being utilized with increasing frequency. This analysis was undertaken to determine the outcome for such patients treated with intensive chemotherapy between 1989–1994, at the Hoag Cancer Center in Newport Beach, CA.Methods During 1989, only patients with metastatic disease who had failed more than two standard breast cancer chemotherapy regimens were considered eligible for such treatment. They received high-dose BCNU/ cyclophosphamide/cisplatinum chemotherapy with autologous bone marrow rescue. After January 1990, patients with metastatic disease were eligible only if they had received limited prior chemotherapy and demonstrated responsiveness to induction chemotherapy. Beginning June 1990, patients with metastatic disease were to receive mitoxantrone and thiotepa (MiTepa) followed by peripheral blood stem cell rescue, then ifosfamide, carboplatin and etoposide (ICE) chemotherapy followed by peripheral blood stem cell rescue. High-risk adjuvant patients were to receive one course of ICE followed by rescue.Results Between 1/89–12/94, 48 breast cancer patients underwent 65 intensive chemotherapy treatments followed by autologous stem cell rescue. During 1989, three of the eight patients with metastatic disease died within 60 days because of therapy-related complications. The longest failure-free survival (FFS) of these eight was 12.2 months, and the longest overall survival (OS) 20.5 months. Since 1/90, one physician has treated 24 patients with metastatic breast cancer, 17 of whom actually underwent two successive transplants with MiTepa/ICE. For the latter group, median FFS is 23.2 months; median OS is 39.7 months. There were no acute deaths, but two patients died > 60 days after initial transplant from therapy-related complications, venoocclusive disease (5.2 months) and myelodysplastic syndrome (30.5 months), while five died of progressive disease at 22.5, 32.8, 39.4, 46.3, and 51.3 months. For the 24 metastatic patients treated 1990–1994, 1-, 2-, and 3-year FFS rates are 86%, 40%, and 17%, respectively, while OS rates are 91%, 80%, and 65%. Of 11 patients treated in the adjuvant setting, only one has relapsed (9.8 months) with follow-up from 3–61 months.Conclusions Modifications made in the program, including selection of patients responsive to induction chemotherapy, transfusion of peripheral blood stem cells, implementation of hematopoietic colony stimulating factors, and use of tandem intensive treatments has been associated with a low rate of acute morbidity and encouraging survival rates.Presented in part at the 16th Annual San Antonio Breast Cancer Symposium, November 5, 1993     

High-dose chemotherapy with autologous stem cell rescue in the outpatient setting

Intensive outpatient care is rapidly becoming the primary mode of care for selected patients undergoing high-dose chemotherapy with autologous peripheral blood stem cell (PBSC) transplantation. Although the traditional inpatient model of care may still be necessary for high-risk patients, published data suggest that outpatient care is safe and feasible during or after administration of high-dose chemotherapy and autologous PBSC transplant. Blood and marrow transplant (BMT) centers have developed programs to provide more outpatient care under three basic models: an early discharge model, a delayed admission model, and a comprehensive, or total, outpatient model. This review will describe these models of care and address the elements necessary for the development of an outpatient BMT program, including patient selection, staff development, and patient and caregiver education. Available supportive care strategies to facilitate outpatient care will also be highlighted. Clinical outcome data and pharmacoeconomic analyses evaluating various outpatient BMT programs, as well as limited quality-of-life evaluations, will be reviewed.     

High-dose chemotherapy with autologous peripheral blood stem cell support in children with malignant diseases

The advanced malignant diseases are rarely responsive to regular chemotherapy. High-dose chemotherapy supported by infusion of autologous peripheral blood stem cell (PBSC) has already shown to have significant activity in these diseases[1]. Nineteen children with advanced malignant diseases being hospitalized in our hospital received high-dose chemotherapy supported by autologous PBSC between June 1992 and February 2005. MATERIALS AND METHODS Patient Characteristics Nineteen childr…     

High-dose tri-alkylator chemotherapy with autologous stem cell rescue in patients with refractory malignancies

Forty patients with refractory solid tumors or non-Hodgkin's lymphoma were treated with high-dose cyclophosphamide, thiotepa, and carmustine (BCNU), followed by autologous stem cell rescue, in a phase I dose escalation study. The dose-limiting toxic effect was delayed drug-induced pulmonary disease, seen in three patients who received 660-750 mg of BCNU/m2 in combination with cyclophosphamide and thiotepa. The early death rate due to toxic effects was 20%; all deaths were attributed to sepsis or respiratory failure. The overall response rate was 63%. The median time to disease progression was 14 weeks. Although this regimen provided effective cytoreduction, its use in heavily pretreated patients with bulky disease is of limited value.     

High-dose chemotherapy and peripheral blood stem cell support in refractory gestational trophoblastic neoplasia

We present retrospectively our experience in the use of high-dose chemotherapy and haematopoietic stem cell support (HSCS) for refractory gestational trophoblastic neoplasia (GTN) in the largest series so far reported. In all, 11 patients have been treated at three Trophoblast Centres between 1993 and 2004. The conditioning regimens comprised either Carbop-EC-T (carboplatin, etoposide, cyclophosphamide, paclitaxel and prednisolone) or CEM (carboplatin, etoposide and melphalan) or ICE (ifosfamide, carboplatin, etoposide). Two patients had complete human chorionic gonadotrophin responses, one for 4 and the other for 12 months. Three patients had partial tumour marker responses for 1-2 months. High-dose chemotherapy and HSCS for GTN is still unproven. Further studies are needed, perhaps in high-risk patients who fail their first salvage treatment.     

High-dose chemotherapy with autologous stem cell rescue for children with recurrent malignant brain tumors

BACKGROUND: High-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) has been reported to be effective in treating children with recurrent central nervous system (CNS) malignancies. METHODS: To evaluate the efficacy and toxicities of HDCT and ASCR, the medical records of 27 children with recurrent CNS malignancies who received such therapy at St. Jude Children's Research Hospital between 1989 and 2004 were reviewed. RESULTS: The median age at diagnosis was 4.5 years (range, 0.4-16.6 years) and that at ASCR was 6.7 years (range, 1.1-18.5 years). Diagnoses included medulloblastoma (13 patients), primitive neuroectodermal tumor (3 patients), pineoblastoma (2 patients), atypical teratoid rhabdoid tumor (2 patients), ependymoma (3 patients), anaplastic astrocytoma (2 patients), and glioblastoma multiforme (2 patients). The 5-year overall and progression-free survival (PFS) rates were 28.2% and 18.5%, respectively. The 5-year PFS rate for patients aged<3 years at diagnosis (57.1%) was significantly better than older patients (5.0%) (P=.019). Among the 6 long-term survivors (5 with M0 disease and 1 with M3 disease at diagnosis), 5 received both radiotherapy and HDCT as part of their salvage regimen; 4 were aged<3 years at diagnosis and had received chemotherapy only as part of frontline therapy. Two patients died of transplant-related toxicities; 44% experienced grade 3 or 4 transplant-related toxicities (toxicities were graded according to the National Cancer Institute Common Toxicity Criteria). CONCLUSIONS: HDCT with ASCR is not an effective salvage strategy for older children with recurrent CNS malignancies. The significantly better outcome in the younger cohort was most likely related to the use of radiotherapy as part of the salvage strategy.     

High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience.

BACKGROUND: T-cell immunophenotype constitutes an unfavorable prognostic factor in aggressive non-Hodgkin's lymphomas. High-dose chemotherapy with autologous stem-cell rescue (HDC/ASCT) is the best salvage therapy for patients with aggressive B-cell lymphomas. However, results with this therapy in peripheral T-cell lymphoma (PTCL) are not well defined. PATIENTS AND METHODS: From January 1990 to December 1999, 115 patients with PTCL underwent HDC/ASCT inside the Grupo Espa?ol de Linfomas/Trasplante Autólogo de Médula Osea (GEL-TAMO) registry. At diagnosis the median age was 41 years and 60% of patients presented with two or three risk factors from the adjusted International Prognostic Index (a-IPI). Thirty-two per cent of patients were transplanted in first complete response (CR), 62% in chemosensitive disease and 5% in refractory disease. RESULTS: Eighty-six per cent of the patients attained a CR and 5% a partial response (PR). With a median follow-up of 37 months (range 1-133), overall survival (OS), time-to-treatment failure (TTF) and disease-free survival (DFS) at 5 years was 56%, 51% and 60%, respectively; for the 37 patients transplanted in first CR, OS and DFS at 5 years were 80% and 79%, respectively. Lactase dehydrogenase (LDH), a-IPI and disease status pre-transplant were associated with outcome. CONCLUSIONS: More than half of patients with chemosensitive disease who were transplanted are expected to be alive at 5 years. We confirm the utility of the pre-transplant IPI system in predicting outcome. Salvage treatment results with HDC/ASCT in PTCL are similar to those found in corresponding aggressive B-cell lymphomas.     

High-dose chemotherapy with hematopoietic stem cell transplantation is effective for nasal and nasal-type CD56+ natural killer cell lymphomas

CD56+ natural killer (NK) cell lymphomas occur frequently in the nasal and nasopharyngeal regions and carry a poor prognosis. We have studied seven cases with NK-cell lymphomas. These lymphomas showed the following immunophenotype: CD56+, CD2+, sCD3- and Epstein-Barr virus-encoded small RNAs (EBERs)+. Six patients had localized (stage I or II) disease involving the nasopharyngeal region, while one had stage III disease. One patient with stage I disease achieved a complete remission (CR) after treatment with involved-field irradiation, but subsequently relapsed and died. The remaining six patients received combination chemotherapy as primary treatment: five patients with localized stage I or II disease and one patient with advanced stage III disease. Responses to initial chemotherapy were generally poor. These six patients received a variety of salvage chemotherapy regimens, but never achieved a CR. Subsequently, four of six patients showed a highly aggressive clinical course and died of disseminated disease within 1 year from the diagnosis. Three of six patients received high-dose chemotherapy supported by syngeneic, autologous or allogeneic peripheral blood stem cell transplantation. Two of the three transplant patients achieved a CR and are now surviving in continuous CR. Our clinical experience suggests that myeloablative high-dose chemotherapy and bone marrow rescue by hematopoietic stem cell transplantation may be an effective salvage treatment modality for refractory NK-cell lymphomas and could be considered as a part of the initial therapy for these patients.     

High-dose chemotherapy with peripheral blood stem cell auto transplantation for an intractable case of mediastinal seminoma

HDC with PBSCT is effective for some intractable cases with malignant neoplasma. We encountered an intractable case of mediastinal seminoma treated by HDC with PBSCT. The patient was a 25-year-old man with mediastinal seminoma. He had undergone chemo-radiotherapy several times and salvage surgery for the mediastinal tumor and chest wall recurrence since September 2001. He was referred to our clinic for management of recurrent seminoma in the chest wall in January 2004. In our clinic, chemo-radiotherapy consisting of cisplatin and etoposide was performed. The tumor size decreased transiently, but re-growth was observed 2 months after chemo-radiotherapy. We then performed HDC with PBSCT twice without any lethal complication. Now, the patient is well and disease-free 1 year after HDC with PBSCT.     

High-dose chemotherapy and stem cell rescue for high-risk Ewing's family of tumors

The prognosis for high-risk Ewing's tumors has been improved by multimodal radiation and chemotherapy. Ewing's family of tumors requires risk-adapted treatment. Risk stratification is dependent on stage, tumor localization and volume, and the pattern of disease spread at the time of diagnosis and the time of relapse. The concepts for high-dose therapy followed by hematopoietic cell transplantation in Ewing's family of tumors are based on dose-response and dose-intensity relationships. This article will discuss the use of high-dose therapy followed by hematopoietic cell transplantation, focusing on recent progress with respect to agent combinations, dose and outcomes of therapy.     

High-dose chemotherapy with autologous peripheral blood stem cell transplantation for the treatment of multiple myeloma refractory to conventional chemotherapy

High-dose chemotherapy with autologous peripheral blood stem cell transplantation was administered to five patients with refractory myeloma. To collect peripheral blood stem cells, apheresis was done by administering doxorubicin 40 mg/m2 on the first day, and etoposide 60 mg/m2 on the first, second, and third days, followed by G-CSF administration to harvest cells. The high-dose chemotherapy consisted of melphalan 60 mg/m2 administered for 4 days and infusion of mononuclear cells. No serious side effects were observed during the clinical course. After transplantation, complete or partial responses were achieved. APBSCT is considered to be a useful method because it had an antitumor effect against multiple myeloma that is refractory to conventional chemotherapy, as well as against multiple myeloma that is sensitive to chemotherapy, and it can be safely performed.     

High-dose rituximab does not negatively affect peripheral blood stem cell mobilization kinetics in patients with intermediate-grade non-Hodgkin's lymphoma

Rituximab, an anti-CD20 human-mouse chimeric monoclonal antibody has been shown to improve response rates when it is combined with standard salvage chemotherapy in patients with relapsed or refractory intermediate-grade B-cell non-Hodgkin's lymphoma. A vast majority of these patients subsequently undergo high-dose therapy followed by stem cell transplantation. However, the impact of rituximab on stem cell mobilization kinetics is not well characterized. The purpose of this study was to study the effect of high-dose rituximab given with chemotherapy on stem cell mobilization in patients with intermediate-grade B-cell non-Hodgkin's lymphoma. Thirty-six patients received ifosfamide, etoposide, and rituximab followed by filgrastim for stem cell mobilization. The chemotherapy regimen was well tolerated. Thirty-four of 36 patients (94%) were able to mobilize at least 2 × 10⁶ CD34+ cells/kg body weight after a median of 2 apheresis procedures. The median CD34+ cell dose collected per kilogram of recipient body weight was 6.5 × 10⁶ (range, 4.65-31.15). All patients who subsequently underwent high-dose chemotherapy and stem cell transplantation experienced sustained engraftment. In conclusion, high-dose rituximab given during stem cell mobilization does not negatively affect stem cell mobilization kinetics.     

High-dose adjuvant chemotherapy with peripheral blood stem cell transplantation for breast cancer with poor prognosis--a pilot study]

Three patients with breast cancer with poor prognosis were treated with high-dose chemotherapy (HD-CT) and peripheral blood stem cell transplantation (PBSCT) as adjuvant treatment. After radical mastectomy, the consolidation chemotherapy with Adriamycin 50 mg/m2, Cyclophosphamide 1,000 mg/m2, Vincristine 1.0 mg/m2 and Methotrexate 200 mg/m2 with Leucovorin rescue was started. Recombinant human granulocyte colony stimulating factor (rhG-CSF) was also added for early recovery from myelosuppression. This combination chemotherapy was given every 3 weeks for 3 courses, and after the 2nd and 3rd courses, peripheral blood stem cells (PBSC) were collected and cryopreserved. HD-CT with Cyclophosphamide 2,000 mg/m2/day, Thio-TEPA 200 mg/m2/day, and Etoposide 300 mg/m2/day, were administered for 3 consecutive days, and after 48 hours of last doses, frozen-thawed PBSC (6.4-8.9 x 10(4)/kg of CFU-GM) were administered. rhG-CSF was also added. HD-CT and PBSCT were well tolerated, recovery from myelosuppression of the HD-CT was very quick and no serious side effects were observed.     

自体外周血干细胞移植支持大剂量化疗治疗淋巴瘤的远期疗效

目的：观察自体外周血造血干细胞移植支持大剂量化疗治疗淋巴瘤的远期疗效。方法：我院1997年8月-2005年4月行自体外周血干细胞移植支持大剂量化疗治疗的淋巴瘤患者共16例,其中男性10例,女性6例;年龄12—61岁,中位年龄30．5岁。所有病例均经病理组织学及免疫组化确诊,其中霍奇金淋巴瘤5例,非霍奇金淋巴瘤11例。移植前状态：处于完全缓解（CR）CR17例,CR22例,部分缓解（PR）PR14例,PR21例。结果：移植后CR9例,PR6例,移植相关死亡1例。全部病例随访至2006年5月,中位随访时间44．5个月（13—89个月）,1例干移植后22个月死于高血压脑卒中,2例分别于移植后12个月及38个月死于复发,其余12例存活至今（其中CR15例,CR22例,PR13例,PR21例,耐药1例）,总生存率75％,无事件生存率62．5％。结论：自体外周血1二细胞移植支持大剂量化疗治疗淋巴瘤,刘提高总生存率和无事件生存率可能有益,值得进一步开展临床研究。     

High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma: long-term follow-up

We previously reported a phase 2 trial of 69 patients with newly diagnosed anaplastic or aggressive oligodendroglioma who were treated with intensive procarbazine, CCNU (lomustine), and vincristine (PCV) followed by high-dose thiotepa with autologous stem cell rescue. This report summarizes the long-term follow-up of the cohort of 39 patients who received high-dose thiotepa with autologous stem cell support. Thirty-nine patients with a median age of 43 (range, 18-67) and a median KPS of 100 (range, 70-100) were treated. Surviving patients now have a median follow-up of 80.5 months (range, 44-142). The median progression-free survival is 78 months, and median overall survival has not been reached. Eighteen patients (46%) have relapsed. Neither histology nor prior low-grade oligodendroglioma correlated with risk of relapse. Persistent nonenhancing tumor at transplant was identified in our initial report as a significant risk factor for relapse; however, long-term follow-up has not confirmed this finding. Long-term neurotoxicity has developed only in those patients whose disease relapsed and required additional therapy; no patient in continuous remission has developed a delayed neurologic injury. This treatment strategy affords long-term disease control to a subset of patients with newly diagnosed anaplastic oligodendroglioma without evidence of delayed neurotoxicity or myelodysplasia.     

自体干细胞移植支持下的大剂量化疗一线治疗恶性淋巴瘤

背景与目的:目前自体干细胞移植(autologous stem cell transplantation,ASCT)支持下的大剂量化疗(high-dose chemotherapy,HDC)已成为复发或难治性恶性淋巴瘤(malignant lymphoma,ML)的标准治疗方法,但是对于一些选择的ML是否可作为一线治疗方案目前尚不明确.本文旨在通过回顾性分析探讨HDC/ASCT作为一线方案治疗ML的疗效.方法:自2000年9月至2007年6月, 连续收治28例ML患者,中位年龄32岁(8～60岁),其中男性17例,女性11例.组织学类型包括24例非霍奇金淋巴瘤,4例霍奇金淋巴瘤.自体外周血干细胞动员采用化疗药物联合重组人粒细胞集落刺激因子方案.HDC方案采用BEAC(BCNU、CTX、Ara-C 、VP-16)方案.随访日期自干细胞回输之日期开始,末次随访日期为2007年7月30日.结果:28例患者均移植成功,重建造血功能.移植前CR 14例,PR 14例,移植后CR 22例,PR 6例.随访截止日期为2007年7月30日,中位随访时间为28个月(1.5～82个月),移植后4例病情进展,其中2例死亡,3年生存率及无进展生存率分别为89%和76%.大剂量化疗期间不良反应均可耐受,无移植相关死亡.结论:HDC/ASCT作为一线方案治疗ML是安全、可行及有效的治疗方法.