Multicenter clinical trial of mitoxantrone in non-Hodgkin's lymphoma and Hodgkin's disease

In this phase II multicenter trial, the efficacy and safety of mitoxantrone (Novantrone; Lederle Laboratories, Wayne, NJ) were evaluated in the treatment of 206 patients with relapsed non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) previously treated with other agents. Sixty-nine percent of the patients had received prior therapy with doxorubicin. The patients received 14 mg/m2 of mitoxantrone every 3 weeks. Nineteen (12%) of the NHL patients and two (7%) of the HD patients had complete responses (CRs). The combined CR and partial response (PR) rates were 37% (60 of 163) for NHL patients and 36% (10 of 28) for HD patients; the median duration of response was 323 days for NHL patients and 209 days for HD patients. The median survival times were 337 days for patients with NHL and 469 days for patients with HD. The median survival time for patients with low-grade NHL was 589 days compared with 298 days for patients with intermediate-grade NHL and 167 days for patients with high-grade NHL. The median time to treatment failure was 73 days for NHL patients and 98 days for HD patients. The major toxicity was myelosuppression, which was moderate and reversible. Nausea, vomiting, and alopecia were mild. There were two cases of congestive heart failure (CHF) considered related to treatment; both patients had received prior treatment with doxorubicin. In this group of heavily pretreated patients, mitoxantrone was effective and well tolerated. Responses were seen with mitoxantrone in patients who had relapsed after prior therapy with doxorubicin and in patients who had failed to respond to prior therapy with doxorubicin. Mitoxantrone should be evaluated in less heavily pretreated patients and should be considered for incorporation into combination chemotherapeutic regimens for the treatment of malignant lymphoma.     

Prolonged daily administration of oral etoposide in lymphoma following prior therapy with Adriamicin,an ifosfamide-containing salvage combination,and intravenous etoposide

Prolonged daily administration of oral etoposide has been reported to be active in refractory lymphoma. The purpose of this phase II trial was to confirm the activity of this schedule of etoposide in a selected group of heavily pretreated patients with non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). A total of 26 patients (20 with NHL and 6 with HD) were entered in the trial; all had previously been treated with an Adriamycin-based chemotherapy, an ifosfamide-containing salvage combination, and i. v. etoposide. Etoposide was given in a fixed oral daily dose of 100 mg over 3 weeks; the weekly dose (500–700 mg) was selected such that the average daily dose was approximately 50 mg/m². Cycles were repeated on day 29. An objective response was seen in 16 patients (62%; 95% confidence interval, 42%–80%), with a complete response (CR) being observed in 3 cases (12%) and a partial response (PR), in 13 (50%). The median duration of PRs was 3 months. CRs lasted for 15 months in one patient and continue at 12+ and 20+ months in the remaining two patients. The overall actuarial survivial for the entire group was 40% at 2 years; the median survival time was 12 months. The main toxicity was myelosuppression; WHO grade 3 or 4 leukopenia and thrombocytopenia developed in 31% and 12% of the patients, respectively. There was no drug-related death. We conclude that oral etoposide is an effective and tolerable palliative treatment for heavily pretreated lymphoma patients.     

Value of oxaliplatin treatment in heavily pretreated patients with non-Hodgkin's lymphoma

In order to assess the efficacy and toxicity profile of oxaliplatin, a third generation platinum derivate active against several solid tumors, we carried out a study in a group of heavily pretreated patients with non-Hodgkin's lymphoma (NHL). Between August 2003 and May 2004, 19 pretreated patients were enrolled in a phase II trial and were treated with oxaliplatin. The drug was administered intravenously on day 1 of a 21-day schedule, at a dose of 130 mg/m² for a total of 6 cycles. One (5%) patient achieved complete remission (CR) and 5 patients (27%) had partial response (PR), thus giving an overall response rate of 32%. The patient in CR suffered from an aggressive B NHL. One of the 5 patients in PR had an aggressive B NHL, whereas the remaining 4 had an indolent B NHL. The treatment was well tolerated with minimal hematologic and extrahematologic toxicity. These data suggest and confirm the efficacy and low toxicity of oxaliplatin in the treatment of patients with heavily pretreated NHL. Further trials using oxaliplatin alone or in combination with other conventional drugs are needed.     

A pilot study of cyclical chemotherapy with high-dose methotrexate and CHOP (MTX-CHOP) in poor-prognosis non-Hodgkin's lymphoma (NHL)

Summary In a pilot study of cyclical chemotherapy in patients with poor-prognosis non-Hodgkin's lymphoma (NHL), high-dose methotrexate (MTX) 1 g/m² with folinic acid rescue was given as initial treatment and then between cycles of a single-arm CHOP combination administered every 4 weeks. Of 21 patients with previously untreated or minimally treated grade 2 (high-grade) histology stage II/III/IV NHL, 13 (62%) achieved complete remission (CR); the CR rate for stage III/IV patients was 56%. Of all 25 patients with grade 2 stage II/III/IV NHL, including previously treated patients, 16 (64%) achieved CR. The median folow-up of patients who completed treatment is currently 22 months and only 1 relapse has been recorded in the CR group. Only five of 24 grade 2 patients given the initial test MTX failed to show any response, and eight patients achieved partial remission (PR) as a result of this single treatment. The response to MTX-CHOP in nine patients with grade 1 (low-grade) histology NHL was poor; only two achieved CR. These findings lend support to other data which indicate a useful role for MTX in the induction chemotherapy of advanced high-grade NHL, though the optimum dosage and drug sequence have yet to be determined.for the Yorkshire Lymphoma Group (YLG)     

Phase II Study of Vincristine Sulfate Liposome Injection (Marqibo) and Rituximab for Patients With Relapsed and Refractory Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma in Need of Palliative Therapy

BackgroundVSLI (Marqibo) is active in advanced non-Hodgkin lymphoma (NHL) and untreated aggressive NHL. Because of its favorable hematologic toxicity profile, VSLI might be useful in patients unable to tolerate myelosuppressive therapies.Patients and MethodsTwenty-two patients with heavily pretreated, advanced CD20⁺ DLBCL or MCL were treated with VSLI 2.0 mg/m², without a dose cap, every 2 weeks plus 4 weekly doses of rituximab 375 mg/m². ORR, complete response (CR), or partial response (PR), was the primary end point. Secondary end points included response duration, time to progression (TTP), and OS. Safety variables included adverse events and neurologic assessments.ResultsThe ORR was 13 of 22 (59%); 6 patients achieved a CR (27%), and 7 patients achieved a PR (32%). Median response duration, TTP, and OS were 147 days, 121 days, and 322 days, respectively. The median number of VSLI doses was 5, the median individual VSLI dose was 3.5 mg, and the maximum cumulative VSLI dose was 43 mg. Grade 3 peripheral neuropathy, febrile neutropenia, and constipation were reported in 4, 2, and 1 patients, respectively.ConclusionVSLI plus rituximab resulted in durable responses in patients with heavily pretreated advanced stage DLBCL and MCL. The toxicity profile was predictable and manageable with limited hematologic toxicity. Despite near-universal previous VCR exposure (96%) and doses of VSLI unachievable with standard VCR treatment, peripheral neuropathy and constipation were modest. This study supports further evaluation of VSLI as a component of DLBCL management.     

Treatment of acute leukemia and malignant lymphoma with (2″R)-4′-O-tetrahydropyranyladriamycin

Summary Eighty-four previously treated adult patients with acute leukemia and malignant lymphoma were treated with (2R)-4-O-tetrahydropyranyladriamycin (THP). THP (10–55 mg/m²) was administered by i.v. bolus injection daily for acute leukemia, and according to three different schedules for malignant lymphoma: daily, weekly or once every 3–4 weeks. Complete and partial remission (CR and PR) were achieved by 1 (5%) and 3 of 19 patients with acute myelogenous leukemia and by 2 (13%) and 3 of 15 patients with acute lymphoblastic leukemia, respectively. All CRs were in the groups receiving 25 mg/m² THP daily. CR and PR were achieved by 6 (14%) and 8 of 42 patients with non-Hodgkin lymphoma (NHL) and by 4 (50%) and 2 of 8 patients with Hodgkin's disease (HD), respectively. No particular sensitivity was found among the subtypes of NHL and HD. Response (CR+PR) was noted in 10 (40%) of 25 patients treated every 3–4 weeks, in 1 (17%) of 6 treated weekly, and in 9 (47%) of 19 treated daily. The major side effects were myelosuppression and gastrointestinal toxicities. Alopecia was observed in only 10 (12%) patients. ECG abnormalities were observed in 7 (10%) patients, all of whom had previously been treated with other anthracyclines. No severe cardiotoxicity was observed.     

Methyl-GAG, ifosfamide, methotrexate and etoposide (MIME) as salvage therapy for Hodgkin's disease and non-Hodgkin's lymphoma. The Swedish Lymphoma Study Group

One hundred and three patients with recurrent or refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) treated with MIME (methyl-GAG, ifosfamide, methotrexate, etoposide) were retrospectively studied. Thirty-seven of the 44 patients with HD, 34/47 with high-grade malignant and 9/12 with low-grade malignant NHL were evaluable for response. Of the 37 evaluable patients with HD, 16 (43%) achieved complete remission (CR) and 4 partial remission (PR), giving a total response rate of 54%. Of the 34 evaluable patients with high-grade NHL, 5 achieved CR and 8 PR, giving a response rate of 38%. Of 9 evaluable patients with low-grade NHL, 2 achieved CR. The main toxicity was leukopenia, thrombocytopenia and infections. Twenty-six per cent of the patients developed septicaemia, which was fatal in 6 cases (6%). We conclude that MIME as salvage regimen can induce complete remissions in lymphoma patients, particularly in HD with previous heavy treatment, and that it is relatively well tolerated.     

Cis-dichlorodiammineplatinum (Cis-platinum) and etoposide (VP-16) in malignant lymphoma — an effective salvage regimen

Summary Response rates in malignant lymphoma after failure of first-line therapy are generally poor. Twenty-five patients with non-Hodgkin's lymphoma (NHL) unresponsive to standard combination chemotherapy were treated with cis-platinum/VP-16. Alo were heavily pretreated, 29% having received three or more different drug regimens. Seventeen patients were evaluable for response. There were five complete remissions (CR) (29%) and four partial remissions (PR) (24%), giving an overall response rate of 53% (36% of all patients treated). The duration of CR was 12–48 weeks. Median survival for responders was 25 weeks (15–95), compared with only 5 weeks (4–17) for non-responders (P=0.002). Toxicity included nausea and vomiting, alopecia, minor renal impairment, and myelosuppression. This was sometimes severe: WBC<1.0x10⁹/l in three patients (18%) and platelets<50x10⁹/l in five patients (29%). The response rate for this combination is superior to that reported for either cisplatinum or VP-16 alone in similar patients (PR only 26% and 20%–30%, respectively). Further investigation is required to define the role of these drugs in the first-line treatment of poor-prognosis NHL.     

Gemcitabine and its combinations in the treatment of malignant lymphoma

Although combination chemotherapy can induce complete remission in a large proportion of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL), 30%-50% of patients will relapse. Gemcitabine has shown promising activity in heavily pretreated patients with HD and NHL even in those who have progressed after autologous stem cell transplantation. Its favorable toxicity profile allows development of combination regimens with other cytotoxic drugs and anti-CD20-targeted therapy, although hematologic toxicities appear to be greater than when gemcitabine is used as a single agent. Prolonged infusion of gemcitabine at a pharmacologically guided dose rate of 10 mg/m2/minute has demonstrated a pharmacokinetic and pharmacodynamic advantage although clinical efficacy of prolonged infusion needs to be established. Thus far, gemcitabine has been mainly tested in relapsed or refractory patients, and its inclusion in front-line therapy may bring about greater benefit. However, as gemcitabine has not been evaluated in randomized studies either alone or in combination with other chemotherapy drugs, its exact role in the treatment paradigm of lymphoma remains to be determined.     

Salvage chemotherapy using a combination of fludarabine and cyclophosphamide for refractory or relapsing indolent and aggressive non-Hodgkin's lymphomas

The prognosis of patients with refractory or relapsing non-Hodgkin's lymphoma (NHL) after primary therapy is poor and multi-drug salvage treatments are associated with less than 60% response rates, usually of short duration. Here we report the results of a phase II study using a fludarabine-cyclophosphamide (FAMP-Cy) combination as a salvage failure regimen in refractory and relapsing low-grade (6) and intermediate-grade (9) NHL patients. Fifteen patients, who had received up to 4 regimens prior to therapy with FAMP-Cy were treated with fludarabine (25 mg/m2) and cyclophosphamide (300 mg/m2) for 3 consecutive days followed by G-CSF (5 microg/kg). The overall response was 74%, 4 achieving complete responses (CR) and 7 partial responses (PR). All patients with low-grade NHL responded (4 CR, 2 PR); 5 patients with intermediate-grade NHL achieved PR lasting for a median of 5 months. The main toxicity encountered was moderate myelosuppression. Three patients had febrile neutropenia, one had drug-induced fever and a single patient developed severe neurotoxicity. Opportunistic infections due to lymphopenia were not seen. The combination of fludarabine and cyclophosphamide used as a salvage regimen showed an impressive response in a small group of heavily pretreated low-grade NHL patients who had previously received a large number of prior regimens. FAMP-Cy had limited effect in a similar group of intermediate-grade NHL patients. Results with this "failure" regimen are encouraging, however further studies are needed in order to confirm these observations in a larger series of patients.     

Non-Hodgkin's lymphoma: natural cell-mediated cytotoxicity correlated with histological classification and prognosis

Non-Hodgkin's lymphoma (NHL) patients classified according to the Rappaport classification system had depressed natural killer (NK) and NK cytotoxic factor activities, antibody-dependent cellular cytotoxicity, active killing potential as well as recycling capacity. The suppression of these activities was not related to the favorable or unfavorable prognosis of the patients. Paramaters of the NK cytotoxic status of the NHL patients did not correlate with the histology or prognosis of the disease.     

Non-Hodgkin's lymphomas in 137 patients aged 70 years or older: a retrospective European Organization for Research and Treatment of Cancer Lymphoma Group Study

The results of a European Organization for Research and Treatment of Cancer (EORTC) retrospective study on non-Hodgkin's lymphoma (NHL) in elderly patients (greater than or equal to 70 years of age) seen in Europe in 1984 are reported. A precodified form was sent to 55 European institutes in order to evaluate the incidence of NHL in the elderly with regard to natural history, treatment-related toxicity, response, and survival. Thirteen institutes participated in the study. One hundred thirty-seven cases of NHL were observed in the elderly during 1984, making up 28% of the total number of NHL seen in those institutes. The median age was 77 years; 21% of the patients had favorable (low-grade) and 73% unfavorable (intermediate- and high-grade) histology, according to the Working Formulation. Stage at presentation was localized (I and II) in 60% and advanced in 37% of the patients. Most of the physicians used standard therapy regimens at reduced doses, from the beginning of the treatment. Sixty patients (44%) underwent a "conservative" treatment (one or two antineoplastic drugs or local field radiotherapy) and 77 (56%) an "aggressive" treatment (polychemotherapy regimens or extended field radiotherapy). Response was similar between the two treatment groups, but severe and lethal toxicity was significantly higher among patients treated with aggressive therapy. Prospective randomized studies are clearly needed to define the optimal treatment in elderly patients with advanced unfavorable NHL.     

Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone alone or with levamisole or with levamisole plus BCG for malignant lymphoma: a Southwest Oncology Group Study

Between 1977 and 1983 the Southwest Oncology Group (SWOG) evaluated chemotherapy alone (cyclophosphamide, doxorubicin, vincristine, prednisone; CHOP) or chemoimmunotherapy (CHOP-levamisole or CHOP-levamisole-BCG) in a randomized prospective clinical trial involving 715 eligible patients with all types of malignant lymphoma (ML). Of 281 evaluable patients with favorable histologic types of ML, 171 (61%) achieved complete remission (CR) and there was no difference in CR rate, CR duration, or survival according to the type of initial treatment. Of 388 evaluable patients with unfavorable histologic types of ML, 194 (50%) achieved CR. Levamisole appeared to adversely affect CR rates in nodular mixed and nodular large-cell lymphoma and CR duration in patients with unfavorable histology ML. Chemoimmunotherapy with levamisole or levamisole-BCG offers no advantage in terms of CR rates, CR duration, or survival compared to CHOP chemotherapy alone, and levamisole may have had an adverse impact on outcome in certain subtypes of ML.     

Activity of esorubicin in recurrent malignant lymphoma: a Southwest Oncology Group study

A phase II trial of esorubicin (4' deoxydoxorubicin) was conducted by the Southwest Oncology Group in 88 assessable patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) at the time of first relapse. Esorubicin was administered at two dose levels: 25 mg/m2 for patients at risk for excessive myelosuppression, and at 30 mg/m2 for all others at 21-day intervals. Overall, 33 of 88 patients (38%) responded to treatment including three complete remissions (CRs; 3%) and 30 partial remissions (PRs; 34%), with the median duration of response lasting 6.2 months. Response rates did not differ significantly by histologic subtype: 31% of 26 patients with favorable NHL, 33% of 43 patients with unfavorable NHL, and 58% of 19 patients with HD. Twelve of 33 responding patients (36%) had relatively durable remissions lasting from 1 to more than 4 years. Leukopenia (less than 3,000 cells per microliter) was seen in 65 of 88 patients (74%) and was severe (less than 1,000 cells per microliter) in 20 of 88 patients (23%). Clinical signs or symptoms of congestive heart failure were not seen and the ejection fraction (EF) fell 10% to 20% in three patients. Esorubicin is an active agent in patients with NHL or HD at the time of first relapse.     

Intensive therapy and autotransplant for patients with an incomplete response to front-line therapy for lymphoma

BACKGROUND:: Patients with Hodgkin's disease (HD) and intermediate or high-gradenon-Hodgkin's lymphoma (NHL) who fail to achieve a completeremission (CR) with standard induction therapy have a poor prognosiswith conventional-dose salvage therapy alone. We examined therole of subsequent intensive therapy and autologous bone marrowtransplantation (ABMT) in patients who demonstrated a responseto conventional-dose salvage therapy. PATIENTS AND METHODS:: Sixty-six patients with either HD (n = 30) or NHL (n = 36) underwentintensive therapy with etoposide (60 mg/kg), intravenous melphalan(160–180 mg/m²) followed by infusion of unpurged autologousbone marrow and/or blood cells. All patients had advanced stageor bulky disease at diagnosis and failed to achieve a CR afteran anthracycline-containing front-line chemotherapy regimen(NHL) or ABVD or equivalent regimen (HD). Patients who achieveda CR after involved-field radiotherapy were excluded. All patientsdemonstrated sensitivity to conventionaldose salvage treatmentbefore advancing to intensive therapy and ABMT. RESULTS:: The CR, partial response (PR) and overall response rate (RR)following ABMT for HD patients was 48%, 17% and 65%, respectively.At a median follow-up of 35 months, the predicted three-yearoverall survival (OS) is 51% (95% CI: 44%–60%) and event-freesurvival (EFS) is 34% (95% CI: 26%–54%). For patientswith NHL, the CR, PR and RR were 68%, 9% and 77%, respectively.At a median follow-up of 28 months, the predicted three-yearOS is 51% (95% CI: 35%–66%) and EFS is 39%(95% CI: 21%–57%). CONCLUSIONS:: Intensive therapy with etoposide and melphalan followed by ABMTresults in prolonged survival in selected patients with lymphomawho fail to achieve a complete remission to front-line chemotherapy.Based on our previous studies of outcome to conventionaldosesalvage chemotherapy, we estimate that of all patients failinginduction therapy, 28% with HD and 15% with NHL will be eventfreeat three years after ABMT. induction failure, Hodglun's disease, non-Hodgkin's lymphoma, refractory lymphoma     

Repeated radioimmunotherapy with 131I-rituximab for patients with low-grade and aggressive relapsed or refractory B cell non-Hodgkin lymphoma

Purpose

A single treatment of ¹³¹I-rituximab in patients with B cell non-Hodgkin lymphoma (NHL) showed a modest rate of response (29 %) in a relatively short duration (median 2.9 months). On the basis of this result, we investigated whether repeated treatment with ¹³¹I-rituximab could improve the response.

Patients and methods

Thirty-one patients with relapsed or refractory B cell NHL received unlabeled rituximab (70 mg) immediately prior to the administration of a therapeutic dose of ¹³¹I-rituximab. The tumor response was evaluated 1 month later by contrast-enhanced ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography. Radioimmunotherapy (RIT) was repeated at 4-week intervals.

Results

A total of 87 cycles of RIT were administered. Repeated RIT yielded twofold increases in response rate (68 %) and in median response duration (8.6 months). This protocol also induced a favorable response in patients with an aggressive histology compared to that induced by a single treatment (50 vs. 9 %, respectively, p = 0.063). The toxicities were principally hematologic with grade 4 thrombocytopenia occurring in 12 % and neutropenia occurring in 17 % of the 85 assessable cycles.

Conclusions

Compared to a single treatment, repeated RIT with ¹³¹I-rituximab increased the response rate and duration for patients with relapsed or refractory B cell NHL, including those with an aggressive histology.     

Cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation in refractory Hodgkin's disease and non-Hodgkin's lymphoma: a dose-finding study

Cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) is a widely used conditioning regimen in autologous bone marrow transplantation (ABMT) of patients with refractory and relapsed lymphoma. However, the maximum-tolerated dose (MTD) of these agents when used in combination has not been systematically explored. We treated 58 patients (28 with non-Hodgkin's lymphoma [NHL], 30 with Hodgkin's disease [HD]) at seven dose levels of CBV. Doses were cyclophosphamide 4,500 to 7,200 mg/m2, BCNU 450 to 600 g/m2, and VP-16 1,200 to 2,000 mg/m2. The MTD was cyclophosphamide 7,200 mg/m2, BCNU 450 mg/m2, and VP-16 2,000 mg/m2. Six hundred milligrams per square meter of BCNU was associated with five of 18 cases of interstitial pneumonitis versus two of 40 at 450 mg/m2 (P = .02). Treatment-related mortality was 5% at dose levels less than or equal to the MTD and 22% at the highest dose. In this heavily pretreated patient population, most of whom had high volume residual disease, complete responses (CRs) to CBV and ABMT occurred in 25% of assessable patients with NHL and 43% of patients with HD. Thirteen of 28 patients with NHL and 14 of 30 with HD remain free from disease progression with median follow-up of 212 and 215 days, respectively. CBV can be administered with acceptable toxicity over a wide range of doses to patients with refractory and relapsed lymphoma.     

恶性淋巴瘤并发特发性血小板减少性紫癜5 例报告

 目的　探讨恶性淋巴瘤 (ML)并发特发性血小板减少性紫癜 (ITP)的诊断与治疗。方法　通过本组病例分析 ML并发 ITP的诊断治疗。结果　本组资料 ML50 0例中并发 ITP5例 ,其中 NHL4例 ,HD1例 ,发生率为 1 % ;ML并发 ITP可于 ML诊断之前、两者同时发生或于肿瘤治疗缓解多年以后发生。强的松或联合化疗可使 ITP缓解 ,但与肿瘤反应不完全平行。结论　提出ML患者并发血小板减少的诊断及合理选择治疗的重要意义。     

Dexa-BEAM is not effective in patients with relapsed or resistant aggressive high-grade non-Hodgkin's lymphoma

The aim of the present study was to evaluate the feasibility and response of the Dexa-BEAM regimen as a salvage therapy followed by high-dose chemotherapy (HDCT) with peripheral blood stem cell transplantation (PBCST) in responding patients with high-grade relapsed or resistant aggressive non-Hodgkin's lymphoma (NHL). Sixteen pretreated patients (mean age 44, range 26-59) with relapsed (8) or resistant (8) NHL were treated with 1-4 cycles of Dexa-BEAM (dexamethasone, BCNU, etoposide, cytarabine, melphalan) in order to attain maximal response. Patients achieving complete response (CR) or partial response (PR) received HDCT with PBSCT. The conditioning regimen used was BEAM. Three patients achieved CR and one patient PR, resulting in an overall response rate of 25%. Three of four responding patients underwent high-dose chemotherapy and were successfully transplanted with autologous blood stem cells. Progressive disease developed in one patient after transplantation. Myelosuppression (WHO grade III- grade IV), the major side effect, was observed in all courses of Dexa-BEAM. Myelosuppression-related infection WHO grade IV occurred in four patients. The protocol was not well tolerated in this heavily pretreated group of patients with four severe myelosuppression-related infections WHO grade IV and one treatment-related death. The overall response rate in this study is not comparable to other salvage regimens published and led to the discontinuation of the trial. In conclusion Dexa-BEAM was only effective in a minority of patients with refractory or relapsed aggressive NHL and was not useful as a cytoreductive regimen prior to HDCT.     

Epirubicin in non-Hodgkin's lymphomas

Epirubicin (Epi-DX), a new analog of doxorubicin, was administered I.V. once q 3 weeks at the dose of 90 mg/m2 to 20 evaluable patients with non-Hodgkin's lymphomas (NHL). Eighty-two percent of patients with favorable histology and 67% with unfavorable histology achieved complete or partial remissions, with an overall response rate of 75%. Gastrointestinal and hematologic toxicity was generally mild to moderate. Reversible ST-T changes were observed only in two patients. Epi-DX has high activity in patients with NHL, and further studies in combination with other agents are recommended.