High dose sequential chemotherapy and autologous stem cell transplantation in patients with relapsed/refractory lymphoma

Although high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for patients with relapsed/refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL), more than 50% of patients will experience relapse following ASCT. High-dose sequential chemotherapy (HDSC) can intensify the conventional salvage treatment and improve the outcome of ASCT by maximal debulking of the tumor load with the use of non-cross resistant drugs, each at their maximal tolerated doses. We conducted a phase II study in 40 patients with relapsed/refractory HD (n = 18) and NHL (n = 22) using HDSC followed by ASCT. Only patients sensitive to salvage chemotherapy were eligible for the protocol, consisting of three phases. Phase I consisted of cyclophosphamide (4.5 g/m²) followed by G-CSF and peripheral blood stem cell (PBSC) collection. Phase II consisted of etoposide (2 g/m²). The transplant phase consisted of mitoxantrone (60 mg/m²) and melphalan (180 mg/m²) followed by PBSC infusion. Eleven out of nineteen patients with B-cell lymphoma received rituximab. Prior to HDSC, 45% of the patients were in complete remission (CR) and 55% were in partial remission (PR). After completion of all phases of the protocol, 35 out of 39 evaluable patients achieved CR (90%) and this was durable in 30 (75%) patients with a projected progression-free survival (PFS) rate at 4 years of 71.7%. Treatment-related mortality rate at day +100 was 2.5% (n = 1). At a median follow-up of 32 months (range, 3 - 61), nine patients relapsed/progressed and eleven patients died. The estimated 4-year PFS and overall survival (OS) were 72.2% and 47.6% in HD patients and 70.3% and 69.4% in NHL patients, respectively. Factors predicting OS were response to conventional salvage therapy and stage prior to salvage therapy. When compared to patients achieving PR, patients who attained CR prior to HDSC had a significantly higher probability of 4-year OS (78.4% vs 31.3%, p = 0.02). Three prognostic subgroups were defined according to the score determined by stage prior to initiation of salvage chemotherapy, remission duration prior to salvage (refractory/early relapse vs. late relapse) and response to salvage. Prognostic score was found to predict OS, PFS and event free survival (EFS). In conclusion, HDSC followed by ASCT is an effective salvage therapy with acceptable toxicity, allowing further consolidation of response attained by conventional salvage therapy.     

择时化疗联合自体骨髓移植治疗非霍奇金淋巴瘤

目的：探讨在自体骨髓（造血干细胞）移植技术支持下应用选择给药时间的高剂量的环磷酰胺、依托泊苷、阿糖胞苷和表柔比星等组成COAE预处理化疗方案治疗预后差的中高度恶性非霍奇金淋巴瘤（NHL）的疗效。方法：观察11例患者应用本方案治疗后造血与免疫功能重建、长期无病生存率、毒副作用及移植相关死亡等,选用Kaplan-Meier生存曲线评估移植后五年无病生存率,COX回归模型分析性别、年龄、预处理方案、移植时状态等对无病重存时间的影响。结果：所有病人均获得造血与免疫功能重建,除3例在移植后1年内复发外,其余病人至2000年5月持续完全缓解（CR）期分别为73、63、35、30、27、20、16、8月。预期5年无病生存率为73%。结论：本法在给药时间上进行了创新,使疗效提高,并减低了高剂量化疗的毒副作用。本法作为有不良预后因素的中高度恶性NHL患者诱导化疗达CR后强化治疗手段的远期疗效显著。     

反应停联合DICE方案治疗难治性复发型非霍奇金淋巴瘤疗效分析

目的:观察反应停联合DICE方案治疗难治性复发型非霍奇金淋巴瘤(NHL)的临床疗效及不良反应.方法:将64例难治性/复发型NHL患者随机分为两组,对照组采用DICE方案治疗,治疗组采用反应停联合DICE方案治疗,以21d为1个周期,对完成4个周期以上者进行疗效评价随访1年和2年生存率.结果:治疗组32例中完全缓解(CR)l5例(46.88%),部分缓解(PR)8例(25.00%),总有效率71.88%;对照组32例中CR 8例(25.00%),PR 6例(18.75%),总有效率为46.88%,两组比较有显著性差异.治疗组1年生存率和2年生存率分别为81.25% (26/32)和56.25% (18/32 ),对照组1年生存率和2年生存率分别为 75.0% (24/32)和40.62%(13/32),较之对照组,治疗组1年生存率有增加趋势,但统计学比较无差异,而2年生存率两组比较有统计学差异(P<0.05).结论:反应停联合DICE方案治疗难治性复发型NHL疗效满意,不良反应可以耐受,值得进一步研究应用.     

Bendamustine is effective in relapsed or refractory aggressive non-Hodgkin's lymphoma.

BACKGROUND: Bendamustine, an alkylating agent with a nitrogen mustard group and a purine-like benzimidazol group, has been shown to be effective in several solid tumors and indolent non-Hodgkin's lymphomas, but has not yet been studied for efficacy in aggressive lymphomas. PATIENTS AND METHODS: We conducted a phase II study in patients with relapsed or refractory high-grade non-Hodgkin's lymphomas, using bendamustine at a dose of 120 mg/m(2) on days 1 and 2, every 3 weeks for up to six cycles. Twenty-one patients were enrolled; 18 were evaluable for response and toxicity, 10 of whom were refractory to previous chemotherapy. RESULTS: With three patients achieving a complete response (at 6, >or=8 and >or=22 months) and five a partial response (three at 2 months, one at 3 months and one at 10 months), the total response rate of the evaluable patients was 44% (eight out of 18; 38% of all patients). Two complete and two partial responders were refractory to prior treatment. In 10 patients, treatment had to be stopped after one to three cycles due to progressive disease or hematological toxicity (n = 2). Non-hematological side effects were mild. Eight (13%) WHO grade 3 and no grade 4 events were observed in 60 evaluable treatment cycles. Hematologic toxicity was moderate (grade 3 and 4): anemia in five cycles (8%), leukopenia in seven (12%) and thrombocytopenia in eight (13%). CONCLUSIONS: Bendamustine as a single agent is effective against aggressive lymphoma, even in cases of refractory disease. Further studies are warranted to determine the significance of bendamustine in the treatment of aggressive lymphomas.     

Efficacy and safety of clofarabine in relapsed and/or refractory non-Hodgkin lymphoma, including rituximab-refractory patients

BACKGROUND:

Currently, no standard therapy exists for patients with relapsed and/or refractory non‐Hodgkin lymphoma (NHL) who are ineligible for transplantation or who have failed after bone marrow transplantation. The authors of this report investigated the safety and efficacy of clofarabine (CLO) in these patients.

METHODS:

In a 2‐step, open‐label study, CLO (as a 1‐hour intravenous infusion given daily for 5 days) was given every 28 days (maximum, 6 cycles). In the phase 1 portion (n = 7; standard 3 + 3 study design), the dose was escalated by 2 mg/m² to determine the maximum tolerated dose (MTD). The phase 2 study (n = 26) was initiated at the MTD, and patients were followed until disease progression.

RESULTS:

Of 33 patients who were enrolled, 31 patients (median age, 69 years) were evaluable; 24% failed after previous stem cell transplantation, and 72% were rituximab‐refractory. The MTD for CLO was 4 mg/m². The overall response rate was 42%. Seven patients (23%) achieved a complete response, and 6 patients (19%) achieved a partial response. The median response duration was 5 months. Among the rituximab‐refractory patients, the overall response rate was 47% (complete response rate, 28%), and the median response duration was 7 months. At a median follow‐up of 14 months, 45% of patients remained alive (median overall survival, 10 months). Toxicity was mainly hematologic (≥60% of patients had neutropenia or thrombocytopenia). Nonhematologic toxicity included tumor lysis syndrome, infection, and renal insufficiency (in 6% of patients each). No treatment‐related mortality was observed.

CONCLUSIONS:

Single‐agent CLO was active and was tolerated well in patients with refractory NHL, including patients in a rituximab‐refractory subset. Reversible myelosuppression was the major toxicity. Study is registered at www.clinicaltrials.gov (NCT00156013). Cancer 2011. © 2010 American Cancer Society.     

Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma. The Hellenic experience

This retrospective study aimed to describe the Hellenic experience on the use of brentuximab vedotin (BV) in relapsed/refractory (R/R) Hodgkin lymphoma (HL) given within its indication. From June 2011 to April 2015, ninety‐five patients with R/R HL, who received BV in 20 centers from Greece, were analyzed. Their median age was 33 years, and 62% were males. Sixty‐seven patients received BV after autologous stem cell transplantation failure, whereas 28 patients were treated with BV without a prior autologous stem cell transplantation, due to advanced age/comorbidities or chemorefractory disease. The median number of prior treatments was 4 and 44% of the patients were refractory to their most recent therapy. The median number of BV cycles was 8 (range, 2‐16), and the median time to best response was the fourth cycle. Fifty‐seven patients achieved an objective response: twenty‐two (23%), a complete response (CR), and 35 patients (37%), a partial, for an overall response rate of 60%. Twelve patients (13%) had stable disease, and the remaining twenty‐six (27%) had progressive disease as their best response. At a median follow‐up of 11.5 months, median progression‐free survival and overall survival were 8 and 26.5 months, respectively. Multivariate analysis showed that chemosensitivity to treatment administered before BV was associated with a significantly increased probability of achieving response to BV (P = .005). Bulky disease (P = .01) and response to BV (P <.001) were significant for progression‐free survival, while refractoriness to most recent treatment (P = .04), bulky disease (P = .005), and B‐symptoms (P = .001) were unfavorable factors for overall survival. Among the 22 CRs, 5 remain in CR with no further treatment after BV at a median follow‐up of 13 months. In conclusion, our data indicate that BV is an effective treatment for R/R HL patients even outside clinical trials. Whether BV can cure a fraction of patients remains to be seen.     

Salvage combination chemotherapy with cytarabine, carboplatin and steroids for relapsed or refractory non-Hodgkin's lymphoma

We have treated 29 patients (19 men and 10 women) with relapsed or refractory non-Hodgkin's lymphoma with a combination of cytarabine (Ara-C), carboplatin (CBDCA) and prednisolone (PSL). The regimen, on days 1 to 3, included Ara-C, 400 mg/m2 i.v.; CBDCA; 250 mg/m2 i.v.; and PSL, 40 mg/m2. Since complete response was achieved in 10 patients (34.5%) and partial response in 9 (31.0%), the total response rate was 65.5%. The 50% survival duration of all patients after the initiation of this therapy was 8 months. The overall 5-year survival rate was 66.7% for those who achieved CR or PR with the Ara-C/CBDCA regimen and received high-dose chemotherapy and autologous hematopoietic stem cell transplantation. Myelosuppression was the major toxicity. Total WBC counts under 1,000/microliter were seen in 67.7% of the courses, and thrombocytopenia under 50,000/microliter was seen in 96.8%. Ara-C/CBDCA has proven to be an effective salvage regimen for patients with relapsed or refractory lymphoma. High-dose chemotherapy and autologous hematopoietic stem cell transplantation should be considered for salvageable patients.     

Sequential doxorubicin and topotecan in relapsed/refractory aggressive non-Hodgkin's lymphoma: results of CALGB 59906

Topoisomerase enzymes are critical components of genomic replication and function to minimize torsional stress on DNA. Sequential administration of a topoisomerase II inhibitor followed by a topoisomerase I inhibitor is potentially synergistic due to increased target enzyme levels. Patients with relapsed or refractory aggressive non-Hodgkin's lymphomas (NHL) were eligible for this phase II study of doxorubicin 25 mg/m² intravenous (IV) on day 1 and topotecan 1.75 mg/m²/day IV on days 3 - 5, every 21 days. The trial objectives included the overall response rate, progression-free survival, and toxicity. Twenty-six patients were enrolled and 25 patients are assessable for toxicity and response. The median age was 58 (range 23 - 74) years. The patients had received a median of two (range one to five) prior regimens, including five patients with a prior stem cell transplant. Five patients (20%, 95% confidence interval 0.07, 0.42) responded with two (8%) complete remissions and three (12%) partial remissions; an additional four (16%) patients had stable disease. Both patients achieving a complete remission had Burkitt's lymphoma. There were no treatment-related deaths. In conclusion, the combination of doxorubicin and topotecan is well tolerated and has modest activity in relapsed/refractory NHL, with occasional patients having a prolonged remission. The activity in Burkitt's lymphoma should be investigated further.     

Potential survival benefit for patients receiving autologous hematopoietic stem cell transplantation after checkpoint inhibitors for relapsed/refractory Hodgkin lymphoma: A real-life experience

In recent years, novel drugs are available for the patients with relapsed/refractory Hodgkin lymphoma (HL), like immune checkpoint inhibitors (CPi). These drugs have been able to rescue a cohort of patients who subsequently could receive an allogeneic stem-cell transplant (SCT). No data were reported for subsequent autologous SCT (ASCT) after CPi. Here, we report our real-life experience in heavily pretreated HL patients undergoing ASCT as consolidation approach after CPi treatment. A retrospective observational study was conducted. Patients had CPi therapy in the context of clinical trials (n = 6) or in the named patient program (n = 7) between July 2014 and November 2019: 9 out of 13 received pembrolizumab and the remaining four underwent nivolumab. A median of 12 cycles (range, 3–16) of CPi therapy were infused. Thirteen patients underwent ASCT after CPi: 11 (84.6%) patients obtained a complete response (CR) and 2 had progression of disease, with an overall response rate of 84.6%. With a median follow-up of 3.3 years (range, 1.1–5.5), only one CR patient had disease relapse after 3.9 months from ASCT, leading to an estimated disease-free survival of 87.5% at 56.9 months. The estimated 5-year progression-free survival was 73.4% and overall survival was 92.3% at 4.8 years, respectively. No unexpected or cumulative toxicity was observed. Our results indicated that ASCT may represent a further effective therapeutic option as consolidation in HL after CPi treatment that today represents the last conventionally recognized therapeutic line.     

Combination chemotherapy with irinotecan and adriamycin for refractory and relapsed non-Hodgkin's lymphoma

Twenty-five patients with relapsed or refractory non-Hodgkin's lymphomawere treated by combination chemotherapy with irinotecan hydrochloride(CPT-11) and adriamycin (ADM): CPT-11, 25 mg/m² on days 1 and 2;ADM, 40 mg/m² on day 3. Nine (36%) of twenty-five patientsachieved CR. Fairly good responses were seen in relapsed B-cell lymphomas (4of 8 in diffuse large B-cell lymphoma and 2 of 2 in follicular lymphoma grade1), and substantial responses in T-cell lymphomas (1 of 4 in peripheral T-celllymphoma and 2 of 7 in adult T-cell leukemia/lymphoma). Leukopenia wasfrequent but tolerable, and diarrhea minimal. Combination chemotherapy witha reduced dose CPT-11 and ADM was useful in the treatment of relapsednon-Hodgkin's lymphoma.     

Paclitaxel plus topotecan treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma

Background:Used as single agents, paclitaxel and topotecan havedemonstrated promising activity in treating patients with relapsed aggressivenon-Hodgkin's lymphoma (NHL). We conducted a phase II clinical trial toinvestigate the activity and tolerability of the combination of bothdrugs. Patients and methods:Patients with refractory or relapsedaggressive NHL who had previously been treated with a maximum of two priorchemotherapeutic regimens were given intravenous infusions of paclitaxel 200mg/m² over three hours on day one and topotecan 1 mg/m²over 30 minutes daily from days one to five. All patients received dailysubcutaneous injections of filgrastim (granulocyte colony-stimulating factor)5 µg/kg starting 24 hours after the last dose of chemotherapy untilneutrophil recovery. Treatments were repeated every three weeks for a maximumof six courses. Patients who achieved partial remission or complete remission(CR) after at least two courses were offered stem cell transplantation,if eligible. Results:Of the 71 patients eligible for this trial, 66(93%) were evaluable for treatment response. The median age was53 years (range 23 to 74 years). Thirty-six percent of the patients hadpreviously been treated with ara-C/platinum-based regimens, and 48%failed to achieve CR after primary induction therapy. Sixty-seven percent ofthe patients had elevated lactate dehydrogenase levels at the time oftreatment initiation. The overall response rate was 48% (95%confidence interval (95% CI): 36%–61%). Patientswho had primary refractory disease had a response rate of 31%, comparedwith 65% for patients who did not. Similarly, the response rate ofpatients who failed to achieve CR after their most recent previous therapy was37%, compared with a 65% response rate in patients who relapsedfrom a first or second CR. The median duration of response was six months. Atotal of 199 courses were given, with a median of three courses per patient.Neutropenia at levels 500 leukocytes per microliter was observed after32% of the courses, and thrombocytopenia at levels 20,000 plateletsper microliter was observed after 17% of the courses. Grade3–4 neutropenic fever occurred after 6% of the courses.Non-hematologic toxic effects were predominantly grade 1–2. Conclusion:The combination of paclitaxel and topotecan is aneffective first or second line salvage therapy for patients with relapsed orrefractory aggressive NHL who had prior anthracycline- or platinum-basedchemotherapy.     

Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma

There is currently no standard salvage chemotherapy regimen in relapsed and refractory lymphoma. Gemcitabine is a novel nucleoside analogue, which acts synergistically with cisplatin both in vitro and in clinical studies. We evaluated the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) in 41 heavily pretreated patients with relapsed and refractory Hodgkin's and non-Hodgkin's lymphoma. The best-achieved response rate (RR) was 79% (95% CI 64-91), with a complete RR of 21%. In patients with chemo-resistant disease, the RR was 63%. Myelosuppression was the main toxicity, the incidence of Grade 3 or 4 anaemia, neutropenia and thrombocytopenia was 17.1, 61.0 and 53.7% respectively. Only one patient had neutropenic sepsis and none of the patients suffered from haemorrhage. Grade 3 or 4 nonhaematological toxicity was minimal and stem cell mobilisation was not inhibited. GEM-P is an effective salvage regimen and its use prior to autologous stem cell transplant warrants further investigation.     

Effective salvage chemotherapy in relapsed or refractory non-Hodgkin's lymphoma

BACKGROUND: Over the last few years, high-dose chemotherapy has been extensivelyinvestigated in relapsing/refractory non-Hodgkin's lymphoma(NHL). However, this approach is reserved to a limited subsetof cases and new conventional-dose second-line chemotherapiesneed to be investigated. PATIENTS AND METHODS: Thirty consecutive out-patients with refractory or recurrentNHL were given polychemotherapy in a regimen consisting of ifosfamide,mitoxantrone and etoposide on day 1 and vindesine, cisplatinumand cytosine arabinoside on day 15: courses were repeated every29 days. Five patients had refractory disease following first-linechemotherapy and 25 were relapsing. RESULTS: The median number of administered cycles was 4 (range 2–8).We observed 16 complete (53%; 95% confidence interval, 34%–72%)and 3 partial remissions, for an overall remission rate of 63%(95% confidence interval, 44%–80%). Responses were seenonly among patients who achieved at least a partial responseduring first-line therapy. The median duration of complete remissionwas 15 months (range 5–47+), whereas median survival ofthe treated patients was 26 months (range 2–50+). Fivepatients were long-term responders after 34+, 35+, 46+, 46+and 47+ months. No-life threatening toxicity was observed. Themain side effects were myelosuppression, nausea/vomiting andalopecia. CONCLUSIONS: The proposed regimen is feasible and effective in terms of completeremission rate and disease-free survival, suggesting that thistreatment may be potentially curative in a subgroup of relapsedpatients with limited tumor burden and normal LDH values. Amore aggressive approach is needed in refractory patients. non-Hodgkin's lymphoma, salvage chemotherapy     

Long-term results favor allogeneic over autologous hematopoietic stem cell transplantation in patients with refractory or recurrent indolent non-Hodgkin's lymphoma.

BACKGROUND: The aim of this study was to compare the outcomes of high-dose therapy (HDT) and allogeneic versus autologous hematopoietic stem cell transplantation (SCT) in patients with refractory or recurrent indolent non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: From January 1991 to March 2000, 112 patients underwent HDT followed by either autologous (68 patients) or allogeneic (44 patients) SCT for refractory or recurrent indolent NHL. Prior conventional chemotherapy had failed in all patients. RESULTS: The two groups were similar with respect to age at transplantation, gender, histological subtypes, number of chemotherapy regimens received before transplantation and International Prognostic Index scores. The median time from diagnosis to transplantation was longer in the autologous than in the allogeneic SCT group (46 versus 27 months, P = 0.002). In the allogeneic SCT group the median follow-up time was 53 months (range 21-113), and the overall survival (OS) and disease-free survival (DFS) rates were 49% and 45%, respectively. After a median follow-up time of 71 months (range 22-109), in the autologous SCT group, the OS and DFS rates were 34% and 17%, respectively. Patients who underwent autologous SCT were more likely to have chemosensitive disease (P <0.001) and were more likely to be in complete remission at the time of transplantation (P = 0.001) than those who underwent allogeneic SCT. However, the probability of disease progression was significantly higher in the autologous SCT group than in the allogeneic SCT group (74% versus 19%, P = 0.003). CONCLUSIONS: Patients who undergo HDT with allogeneic SCT for refractory or recurrent indolent NHL have lower relapse rates but higher treatment-related mortality rates than patients who undergo autologous SCT. However, with the development of non-myeloablative preparative regimens, which can decrease treatment-related mortality, patients with recurrent indolent NHL should be considered for controlled trials of allogeneic transplantation if they have a human leukocyte antigen-identical donor.     

Risk of therapy-related myelodysplastic syndrome/acute leukemia following high-dose therapy and autologous bone marrow transplantation for non-Hodgkin's lymphoma.

BACKGROUND: Several recent reports have suggested that patients with non-Hodgkin's lymphomas (NHL) who undergo autologous stem cell transplantation (ASCT) are at increased risk of developing therapy-related myelodysplastic syndrome (tMDS) and acute myelogenous leukemia (tAML). PATIENTS AND METHODS: We analyzed 493 patients with NHL who underwent ASCT at The University of Texas M.D. Anderson Cancer Center between January 1990 and August 1999. RESULTS: With a median follow-up time of 21 months after HDT, 22 patients developed persistent cytopenia in at least one cell line with morphologic or cytogenetic evidence of tMDS or tAML. Univariate analysis identified prior fludarabine therapy, bone marrow involvement with lymphoma, and total body irradiation (TBI) as significant risk factors for the development of tMDS/tAML (P <0.05). Multiple logistic regression analysis showed that TBI was independently associated with an increased risk of developing tMDS/tAML (P <0.01). Further analysis of the patients who received TBI revealed that patients receiving TBI in combination with cyclophosphamide and etoposide were more likely to develop tMDS/tAML than those who received TBI with cyclophosphamide or thiotepa (P <0.01). The median survival of patients developing tMDS/tAML was 7.5 months (range 0-32 months). CONCLUSIONS: TBI, especially when used in combination with cyclophosphamide and etoposide as the pretransplant conditioning regimen, is a significant risk factor for the development of tMDS/tAML.     

GDP方案治疗复发性或难治性非霍奇金淋巴瘤临床分析

目的:观察GDP方案(GEM+DDP+DXM)治疗复发性或难治性非霍奇金淋巴瘤的疗效和不良反应。方法:2008年1月至2010年3月安徽医科大学附属六安医院肿瘤中心收治的23例复发性或难治性非霍奇金淋巴瘤患者,给予吉西他滨(GEM)1000 mg/m2静脉滴注,d1,8;顺铂(DDP)25mg/m2静脉滴注,d1-3;地塞米松(DXM)20-40mg静脉滴注,d1-3,21天为1周期,2个周期后评价疗效,并随访疾病进展情况。结果:23例患者中,14例缓解(60.9%),其中完全缓解5例(21.7%),部分缓解9例(39.1%)。23例患者中位肿瘤进展时间(TTP)为5.0个月(95%CI:3-8个月)。主要不良反应为骨髓抑制和轻中度消化道反应。骨髓抑制表现为3-4级白细胞减少2例;3-4级血红蛋白减少1例;3-4级血小板减少1例,并发出血。结论:GDP方案治疗复发性或难治性非霍奇金淋巴瘤是一个有效,相对不良反应较轻的二线挽救方案。     

Aclarubicin-combined combination chemotherapy in patients with refractory or relapsed non-Hodgkin's lymphoma

Patients with lymphoma who became refractory or resistant to standard chemotherapy including anthracyclines were treated with aclarubicin-combined chemotherapy including VP-16, ifosfamide, and carboquone in a multicenter study. Twenty-one patients were entered in this study, and 18 of them were evaluable. The median age was 52 years old (range 27-74), and there were 17 male and 3 female patients. The vast majority of patients were diagnosed as having diffuse lymphoma, of which 10 cases had large cell type. Surface markers were measured in 8 patients, of whom 4 had T-cell lymphoma. Remission was attained in 3 of 18 patients (17%) with one complete and lasting remission with T-cell lymphoma. In conclusion, the response rate in this study was poor, but this type of combination chemotherapy might be considered in patients with T-cell lymphoma.