L-Asparaginase—Based Regimen in the Treatment of Refractory Midline Nasal/Nasal-Type T/NK-Cell Lymphoma

Nasal, nasal-type T-cell/natural killer cell (T/NK-cell) lymphoma is a rare disease, and its prognosis is poor. Between March 1992 and March 2002 we investigated a new L-asparaginase-based salvage regimen to treat the disease and improve response to treatment and 5-year overall survival rate. Eighteen patients with refractory midline nasal, nasal-type T/NK-cell lymphoma, who were resistant to a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-like regimen, received an L-asparaginase-based salvage regimen (L-asparaginase, vincristine, and dexamethasone). Primary involved field radiation was given to the patients after chemotherapy. Ten (55.6%) of the patients achieved complete response (CR). Five patients (27.8%) achieved partial response (PR). The overall response rate (CR + PR) was 83.3%. The 5-year overall survival rate was 55.6%. Results of the preliminary clinical study indicated that the L-asparaginase-based salvage regimen significantly improved the response rate and 5-year survival rate. The findings suggested that the therapy is a promising new salvage regimen for treating refractory midline nasal, nasal-type T/NK-cell lymphoma.     

GDP (Gemcitabine,Dexamethasone, and Cisplatin) Is Highly Effective and Well-Tolerated for Newly Diagnosed Stage IV and Relapsed/Refractory Extranodal Natural Killer/T-Cell Lymphoma,Nasal Type

This study was conducted to evaluate the effectiveness and tolerance of GDP (gemcitabine, dexamethasone, and cisplatin) regimen in patients with newly diagnosed stage IV and relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type (ENKTL).The study enrolled 41 ENKTL patients who received GDP regimen at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2008 and January 2015.The disease status was newly diagnosed stage IV in 15 patients and relapsed/refractory in 26 patients. The median number of cycles of chemotherapy per patient was 6 (range, 2–8 cycles). The overall response rate and complete-remission rate were 83.0% (34/41) and 41.5% (17/41), respectively. After a median follow-up of 16.2 months, 1-year progression-free survival rate and 1-year overall survival rate for the whole cohort were 54.5% and 72.7%. Grade 3 to 4 adverse events included neutropenia (34.1%), thrombocytopenia (19.5%), and anemia (14.6%).Our study has suggested high efficacy and low toxicity profile of GDP regimen in patients with newly diagnosed stage IV and relapsed/refractory ENKTL.     

Long-term follow-up in patients treated with Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease

Several studies have focused on investigation of the optimal salvage regimen to induce maximum response before autologous stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin's disease (HD). However, in most of these studies, the follow-up is relatively short. In the present study, we report on long-term results of 55 consecutive patients with HD who received Mini-BEAM [BCNU (carmustine), etoposide, cytarabine, melphalan] as salvage therapy before ASCT. Eleven patients were refractory to front-line therapy, 17 were partial responders, and 27 patients had relapsed from HD. Twenty-eight patients achieved complete response, and 18 achieved partial response with a median of two cycles of Mini-BEAM, giving a total response rate of 84%. Significant factors predicting poor response (P < 0.05) were: initial treatment with MOPP (mechloroethamine, oncovin, procarbazine, prednisolone), > or = two previous chemotherapy regimens and three disease characteristics at Mini-BEAM treatment: presence of B symptoms, extranodal involvement or low serum albumin. However, only the last two factors retained independent influence on multivariate analysis. In total, 45/55 patients have been transplanted. Median follow-up after Mini-BEAM administration for living patients is 68 months. At the time of reporting, 31 out of 55 patients (56.4%) are still alive, 21 patients (38%) have relapsed, three (5.4%) have developed secondary neoplasias, and five have died of other complications not related to disease progression. The actuarial 7-year overall survival (OS) was 52%, the progression-free survival (PFS) 54% and the event-free survival (EFS) 36%. The response to Mini-BEAM was the most important prognostic factor for predicting the long-term probability of surviving the disease: none of the eight patients who did not respond to Mini-BEAM were alive at 3 years. On multivariate analysis, response to Mini-BEAM and extranodal involvement before Mini-BEAM had a significant influence on OS. Our results show the safety and efficacy of Mini-BEAM before ASCT for refractory or relapsed HD patients.     

Study on effectiveness of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related non-Hodgkin's lymphoma

Non-Hodgkin's lymphoma (NHL) remains the second most common malignant complication in patients with human immunodeficiency virus (HIV) infection. Even though NHL is commonly chemosensitive to primary treatment, failure or relapse still occurs in a large number of patients. We conducted this retrospective study to evaluate the efficacy and safety of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory AIDS-related NHL (AIDS-NHL). Forty-eight patients with relapsed or refractory AIDS-NHL were treated with intravenous combination chemotherapy with GDP. The overall objective response rate was 54.1?% (95?% confidence interval, CI, 40.1–68.3?%), with 10 complete responses and 16 partial responses. The 2-year overall survival rate (OS) was 70.8?% (95?% CI 58.0–83.7?%), and the 5-year OS was 41.7?% (95?% CI 27.7–55.6?%). The 2-year progression-free survival rate (PFS) was 37.5?% (95?% CI 23.8–51.2?%), and the 5-year PFS was 25.0?% (95?% CI 12.8–37.3?%). The median progression-free survival was 8.8?months (95?% CI 0–20.3?months), and the median overall survival was 40.6?months (95?% CI 22.6–58.6?months). Patients with B cell tumors who relapsed but had no B symptoms were clinical stage I/II, had infiltration fewer than two extranodal sites, had CD4⁺ counts >200 cells/μL, and had lactate dehydrogenase (LDH) less than the upper limit of normal benefited from GDP. The level of LDH had a significant impact on the response rate to chemotherapy with GDP (P?=?0.015). Myelosuppression was the main side effect; the incidence of grade 3–4 anemia was 8.3?%; leukopenia, 37.5?%; and thrombocytopenia, 48.3?%. Univariate and multivariate analyses were performed to determine variables for OS and PFS. This study confirms that GDP is an effective and safe salvage regimen in relapsed or refractory AIDS-NHL, was associated with modest declines in CD4⁺ lymphocyte counts, and did not promote HIV-1 viral replication.     

Clinical implications of plasma Epstein-Barr virus DNA in early-stage extranodal nasal-type NK/T-cell lymphoma patients receiving primary radiotherapy

The clinical value of plasma Epstein-Barr virus (EBV) DNA has not been evaluated in patients with early-stage extranodal nasal-type NK/T-cell lymphoma (NKTCL) receiving primary radiotherapy. Fifty-eight patients with stage I disease and 11 with stage II disease were recruited. High pretreatment EBV-DNA concentrations were associated with B-symptoms, elevated lactate dehydrogenase levels, and a high International Prognostic Index score. EBV-DNA levels significantly decreased after treatment. The 3-year overall survival (OS) rate was 82.6% for all patients. Stage I or II patients with a pretreatment EBV-DNA level of ≤ 500 copies/mL had 3-year OS and progression-free survival (PFS) rates of 97.1% and 79.0%, respectively, compared with 66.3% (P = .002) and 52.2% (P = .045) in patients with EBV-DNA levels of > 500 copies/mL. The 3-year OS and PFS rates for patients with undetectable EBV-DNA after treatment was significantly higher than patients with detectable EBV-DNA (OS, 92.0% vs 69.8%, P = .031; PFS, 77.5% vs 50.7%, P = .028). Similar results were observed in stage I patients. EBV-DNA levels correlate with tumor load and a poorer prognosis in early-stage NKTCL. The circulating EBV-DNA level could serve both as a valuable biomarker of tumor load for the accurate classification of early-stage NKTCL and as a prognostic factor.     

An effective salvage treatment using ifosfamide, etoposide, cytarabine, dexamethasone, and rituximab (R-IVAD) for patients with relapsed or refractory aggressive B-cell lymphoma

We evaluated the efficacy and toxicity of a new salvage regimen, consisting of rituximab (375?mg/m(2), day 1), ifosfamide (1500?mg/m(2) on days 3-7), etoposide (150?mg/m(2), days 3-5), cytarabine (100?mg/m(2), days 3-5) and dexamethasone (40?mg/body, days 3-5) (R-IVAD) for relapsed or refractory aggressive B-cell lymphoma. In this study, a total of 32 patients with a median age of 64?years (range 38-79) who received an average of 2.6 cycles of R-IVAD from 2001 to 2009 in our institution were retrospectively analyzed. R-IVAD was given every 3?weeks up to a total of three courses with support by granulocyte colony stimulating factor. The overall response rate was 72%, with 56% complete response. On a median follow-up of 16?months (range 2-99), estimated 2-year overall survival (OS) and event-free survival were 55% and 36%, respectively. Of these patients, 10 successfully proceeded to consolidating high-dose chemotherapy followed by autologous stem cell transplantation, accounting for 90% of the 2-year OS. No treatment-related mortality was observed during the investigation. We, therefore, conclude that R-IVAD regimen is a safe and efficacious alternative for patients with relapsed or refractory aggressive B-cell lymphoma.     

High-dose therapy and autologous stem cell transplantation in relapsed and refractory Hodgkin's disease: outcome based on a prognostic model

We evaluated the results of high-dose therapy (HDT) and autologous hematopoietic stem cell transplantation (ASCT) in patients with relapsed or primary refractory Hodgkin's disease (HD), using a previously reported prognostic model based on the presence of three poor prognostic factors at the start of salvage therapy/preparative regimen: B symptoms, extranodal disease and the duration of last complete response of less than 1 year. Based on this model, the patients were divided into low-risk and high-risk groups. Between 1993 and 2001, 24 patients with HD were treated with HDT and ASCT. Eighteen of the 24 patients had 0-1 risk factors (low-risk group) and 6 patients had 2-3 risk factors (high-risk group). Using Kaplan-Meier analysis, after a median follow-up of 40.5 months, the progression-free survival (PFS) was 48%, and the overall survival (OS) was 55%. PFS in the low-risk group was 56%, and in the high-risk group 17% (p < 0.001). OS in the low-risk group was 68% and in the high-risk group it was 18% (p < 0.001). The 100-day transplant-related mortality for the entire group was 16%. Our results are comparable to those reported in previous clinical trials for patients with refractory and relapsed HD treated with HDT and ASCT. The use of a prognostic model appears useful for predicting the outcome of HDT and ASCT for HD patients, and may play an important role in choosing the appropriate therapy for these patients.     

Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study

Extranodal NK/T-cell lymphoma, nasal type, is a rare and highly aggressive disease with a grim prognosis. No therapeutic strategy is currently identified in relapsing patients. We report the results of a French prospective phase II trial of an L-asparaginase-containing regimen in 19 patients with relapsed or refractory disease treated in 13 centers. Eleven patients were in relapse and 8 patients were refractory to their first line of treatment. L-Asparaginase-based treatment yielded objective responses in 14 of the 18 evaluable patients after 3 cycles. Eleven patients entered complete remission (61%), and only 4 of them relapsed. The median overall survival time was 1 year, with a median response duration of 12 months. The main adverse events were hepatitis, cytopenia, and allergy. The absence of antiasparaginase antibodies and the disappearance of Epstein-Barr virus serum DNA were significantly associated with a better outcome. These data confirm the excellent activity of L-asparaginase-containing regimens in extranodal NK/T-cell lymphoma. L-Asparaginase-based treatment should thus be considered for salvage therapy, especially in patients with disseminated disease. First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma warrants evaluation in prospective trials. This trial is registered at www.clinicaltrials.gov as #NCT00283985.     

Outcome after autologous stem cell transplantation in primary refractory or relapsed Hodgkin lymphoma—a long-term follow-up single center experience

Autologous stem cell transplantation (autoSCT) can achieve long-term remission in primary refractory or relapsed Hodgkin lymphoma (r/r HL); however, still up to 50% of patients relapse after autoSCT. In this retrospective analysis, we investigated the impact of autologous stem cell transplantation in a consecutive, unselected cohort of primary refractory and relapsed Hodgkin lymphoma patients (n = 66) with the majority of patients treated in the pre-brentuximab vedotin and immune checkpoint inhibitor era. In our cohort, a 5-year overall survival (OS) from autoSCT of 59.5% and a 5-year progression-free survival (PFS) after autoSCT of 46.1% was achieved. Multivariate analysis revealed primary refractory disease and early relapse (< 12 months) after initial therapy as well as the presence of B symptoms at relapse as independent risk factors associated with a higher risk for relapse and an inferior PFS and OS. Several other clinical factors, including the presence of extranodal disease at relapse and failure to achieve a complete response to salvage chemotherapy, were associated with a trend towards an inferior survival. Patients relapsing after autoSCT had a particularly poor outcome, regardless of eligibility to undergo allogeneic stem cell transplantation (alloSCT). We further evaluated recently published prognostic models for r/r HL patients undergoing autoSCT and could validate several risk scores in our independent “real world” cohort.     

Survival benefit with salvage radiotherapy for patients with locoregionally recurrent extranodal NK/T cell lymphoma, nasal type

The purposes of this study are to evaluate prognosis in patients with locoregionally recurrent extranodal nasal-type NK/T cell lymphoma (NKTCL) and to determine the value of salvage radiotherapy. Forty-two patients with NKTCL who developed first locoregional recurrence with (n?=?13) or without (n?=?29) systemic failure were reviewed. Retreatment included chemotherapy (n?=?20), radiotherapy (n?=?13), and radiotherapy plus chemotherapy (n?=?9). Fifteen patients were reirradiated for localized recurrent disease. The 5-year overall survival (OS) rate after recurrence was 40 %, with a median survival of 26 months. The 2-year OS rate and median OS were 68 % and 36 months for locoregional recurrence only, compared with 31 % and 14 months for both locoregional and systemic recurrence, respectively (p?=?0.034). Subgroup analysis for patients with localized recurrent disease revealed an improved OS with radiotherapy. The 2-year and 5-year OS rates were 77 and 69 % for radiotherapy, respectively, compared with a 2-year OS rate of 50 % and median OS of 16 months for chemotherapy alone (p?=?0.006). Patients with localized recurrence had a better prognosis than those with systemic recurrence. Salvage radiotherapy or reirradiation resulted in a favorable prognosis for patients with localized recurrent disease.     

Autologous stem cell transplant for early relapsed/refractory Hodgkin lymphoma: results from two transplant centres

Prior series have demonstrated that early relapsed (within 1 year) or refractory Hodgkin lymphoma (HL) is associated with poor prognosis. To determine the outcome for patients with early relapsed/refractory HL in the modern era, we combined data from two large transplant centres, Cleveland Clinic Taussig Cancer Institute (CCTCI) and Memorial Sloan-Kettering Cancer Center (MSKCC), and analysed consecutive patients transplanted for relapsed/refractory HL following induction failure or remission durations of <1 year. Two hundred and fourteen patients were analysed and the event-free survival (EFS) and overall survival (OS) at 6 years for all patients were 45% and 55%, respectively. Factors significant for prognosis in multivariate analysis were extranodal disease and bulky disease (≥5 cm). Patients with 0, 1, or 2 risk factors achieved 6 year EFS of 65%, 47%, and 24% and 6 year OS of 81%, 55%, and 27%, respectively. Patients with the sole risk factor of early relapsed/refractory disease achieved good outcomes in this large series; however the presence of bulk and/or extranodal disease significantly reduced EFS and OS. Patients with these additional risk factors are best suited for clinical trials investigating novel salvage regimens and post-transplant maintenance strategies.     

The prognostic significance of lymphopenia in peripheral T-cell and natural killer/T-cell lymphomas: a study of 826 cases from the International Peripheral T-cell Lymphoma Project

Lymphopenia is a marker of inferior survival in patients with various malignancies. However, the prognostic significance of lymphopenia in peripheral T-cell lymphoma (PTCL) is unclear. We analyzed the prognostic significance of lymphopenia in 826 patients with different types of PTCL and natural killer/T-cell lymphoma (NKTCL) from the International Peripheral T-cell Lymphoma Project. Lymphopenia was defined as an absolute lymphocyte count of less than 1,000 cells per microliter. The overall frequency of lymphopenia was 35.3%, ranging from 21.1% in ALK(+) anaplastic large cell lymphoma (ALCL) to 47.5% in angioimmunoblastic T-cell lymphoma (AITL). Lymphopenia was independently associated with an inferior overall survival (OS) in patients with the lymphoma type of adult T-cell leukemia/lymphoma (ATLL), with a 2-year OS of 15% versus 40% for those without lymphopenia (P < 0.001). Lymphopenia was also an adverse predictor of survival in PTCL, not otherwise specified, but was associated with other unfavorable prognostic factors. A trend toward inferior survival for lymphopenic patients was also observed in AITL, ALK(-) ALCL and extranasal NKTCL lymphoma, whereas no difference in survival was found in nasal NKTCL, ALK(+) ALCL, or enteropathy-associated T-cell lymphoma. In this study, lymphopenia was identified as a new adverse prognostic factor in the lymphoma type of ATLL.     

Second-line salvage chemotherapy for transplant-eligible patients with Hodgkin's lymphoma resistant to platinum-containing first-line salvage chemotherapy

Background

The management of patients with relapsed or refractory Hodgkin’s lymphoma who achieve less than a partial response to first-line salvage chemotherapy is unclear. The objective of this study was to evaluate response and outcomes to second-line salvage and autologous stem cell transplantation in patients not achieving a complete or partial response to platinum-containing first-line salvage chemotherapy.

Design and Methods

Consecutively referred transplant-eligible patients with relapsed/refractory Hodgkin’s lymphoma after primary chemotherapy received gemcitabine, dexamethasone, and cisplatin as first salvage chemotherapy. Those achieving a complete or partial response, and those with a negative gallium scan and stable disease with bulk <5 cm proceeded to high-dose chemotherapy and autologous stem cell transplantation. Patients with progressive disease or stable disease with a positive gallium scan or bulk ≥5 cm were given second salvage chemotherapy with mini-BEAM (carmustine, etoposide, cytarabine, melphalan). Patients who responded (according to the same definition) proceeded to autologous stem cell transplantation.

Results

One hundred and thirty-one patients with relapsed/refractory Hodgkin’s lymphoma received first-line salvage gemcitabine, dexamethasone, and cisplatin; of these patients 99 had at least a partial response (overall response rate 76%). One hundred and twelve (85.5%) patients proceeded to autologous stem cell transplantation, while the remaining 19 (14.5%) patients received mini-BEAM. Among these 19 patients, six had at least a partial response (overall response rate 32%), and nine proceeded to autologous stem cell transplantation. The remaining ten patients received palliative care. Seven of the nine patients transplanted after mini-BEAM had a subsequent relapse. Patients receiving second salvage mini-BEAM had poor outcomes, with a 5-year progression-free survival rate of 11% and a 5-year overall survival rate of 20%.

Conclusions

Patients who require a second salvage regimen to achieve disease control prior to autologous stem cell transplantation have a relatively poor outcome and should be considered for alternative treatment strategies.     

Salvage chemotherapy with mini-BEAM for relapsed or refractory Hodgkin's disease prior to autologous peripheral blood stem cell transplantation.

BACKGROUND AND OBJECTIVE: High-dose chemotherapy and autologous bone marrow transplantation (ABMT) has become the standard approach for most patients with relapsed or refractory Hodgkin's disease. Disease status at transplant has been correlated with outcome following ABMT. In light of this, we employ mini-BEAM (BCNU, etoposide, cytarabine and melphalan) salvage therapy in order to achieve a state of minimal residual disease prior to transplantation. DESIGN AND METHODS: From February 1992 to June 1998 twenty-four patients receiving mini-BEAM therapy for resistance or relapse of their Hodgkin's disease were included. Four patients had obtained no response with initial chemotherapy (refractory), eight had obtained an incomplete response, seven were in first relapse and five in second or subsequent relapse. Fifteen patients received mini-BEAM as first salvage chemotherapy regimen. The remaining nine patients had previously been exposed to a median of one salvage regimen. Patients received a median of three cycles of mini-BEAM. RESULTS: Sixteen patients achieved complete remission and four partial remission, yielding an overall response rate of 83%. No significant differences in response were observed between patients who received mini-BEAM as initial salvage therapy and those who had received a prior salvage regimen. Eighteen out of the twenty responding patients went on to intensive therapy and peripheral blood stem cell transplantation. With a median follow-up of 52 months, the cumulative probability of 7-year overall survival is 71% for the responders and that of the 6-year disease-free survival is 42%. No treatment-related deaths were observed. INTERPRETATION AND CONCLUSIONS: Mini-BEAM is an effective salvage regimen with moderate toxicity that may be useful for cytoreduction prior to stem cell procedures.     

Effectiveness of gemcitabine,pegaspargase, cisplatin,and dexamethasone (DDGP) combination chemotherapy in the treatment of relapsed/refractory extranodal NK/T cell lymphoma: a retrospective study of 17 patients

The prognosis of extranodal nature killer (NK)/T cell lymphoma (ENKL) is dismal because of its aggressive course and multidrug resistance. Currently, for patients with relapsed/refractory ENKL, l-asparaginase-based regimens such as l-asparaginase, ifosfamide, methotrexate, etoposide, and dexamethasone (SMILE) or l-asparaginase, methotrexate, and dexamethasone (AspaMetDex) are recommended. We retrospectively investigated the efficacy and safety of gemcitabine, pegaspargase, cisplatin, and dexamethasone (DDGP) combination chemotherapy in the treatment of 17 relapsed/refractory ENKL patients. Clinical data from these patients were collected and analyzed. The primary end point was overall response rate (ORR). All patients were subjected to 2 to 6 cycles of DDGP chemotherapy, and the median number of cycles of DDGP regimen administrated was four. The ORR was 88.2 % (15/17), with nine patients (52.9 %) achieved complete response (CR) and six patients (35.3 %) achieved partial response (PR). The median follow-up time was 17 months (range 2–28 months). The 1-year overall survival (OS) rate and 1-year progression-free survival (PFS) were 82.4 and 64.7 %, respectively. For those CR responders, the median PFS was 17 months. Grade 3/4 neutropenia occurred in nine patients (52.9 %) and grade 3/4 thrombocytopenia occurred in six patients (35.3 %). DDGP combination chemotherapy produces favorable outcomes in relapsed/refractory ENKL, and more attention should be paid to treatment-related myelosuppression. Further prospective trials are expected to define the efficacy.     

Intensified preparative regimens and autologous transplantation in refractory or relapsed intermediate grade non-Hodgkin's lymphoma

Between September 1986 and June 1998, 99 patients with relapsed or refractory IGL received intensified preparative therapy and underwent autologous transplantation at a single institution. Two intensified preparative regimens were used: cyclophosphamide, etoposide, total body irradiation (CY-VP-TBI) (n = 66) and cyclophosphamide, BCNU, etoposide (CBV) (n = 33). As clinical features and results were not different for the two preparative regimens, results were combined. For all patients undergoing autologous transplantation, 5-year actuarial overall survival (OS) was 34% +/- 6%; 5-year event-free survival (EFS) was 26% +/- 5%. For patients who responded to primary therapy, salvage therapy, or both, OS was 42% +/- 7%; for non-responders to prior therapy, OS was 14% +/- 7%, P < 0.025. OS was better among patients responding to salvage therapy (50% +/- 9%), than among patients who had a complete response to initial therapy, but failed to respond or were untested/unevaluable with respect to salvage therapy (26% +/- 10%; P < 0.025). On multivariate analysis, response to salvage therapy was associated with survival following autologous transplantation (P < 0. 005). Treatment related mortality was 9% overall and only 6% after G-CSF and GM-CSF were introduced into routine clinical practice. High-intensity preparative therapy is highly effective, with acceptable treatment-related mortality, in patients with IGL who have responded to induction therapy, salvage therapy, or both. The best responses are observed in patients responding to salvage therapy. Randomized prospective studies will be needed to further define the role of intensified preparative regimens. Bone Marrow Transplantation (2000) 25, 257-262.     

Homoharringtonine in combination with cytarabine and aclarubicin in the treatment of refractory/relapsed acute myeloid leukemia: a single-center experience

To assess the efficacy and toxicity of HAA regimen (Homoharringtonine 4 mg/m²/day, days 1–3; cytarabine 150 mg/m²/day, days 1–7; aclarubicin 12 mg/m²/day, days 1–7) as a salvage therapy in the treatment of refractory and/or relapsed acute myeloid leukemia (AML), 46 patients with refractory and/or relapsed AML, median age 37 (16–65) years, participated in this clinical study. The median follow-up was 41 (10–86) months. Eighty percent of patients achieved complete remission (CR), and the first single course of re-induction HAA regimen resulted in CR rate of 76.1 %. The study protocol allowed two courses of induction. The CR rates of patients with favorable, intermediate and unfavorable cytogenetics were 90 %, 88.9 %, and 37.5 %, respectively. For all patients, the estimated 3-year overall survival (OS) rate was 42 %, and the estimated relapse free survival (RFS) at 3 years for the 36 CR cases was 49 %. The toxicities associated with HAA regimen were acceptable. HAA is a good choice in cases with refractory/relapsing AML for salvage chemotherapy, preferably with a high-efficacy and low-toxicity profile.     

Long-term results of 60 patients with pathologic stage I & IIA Hodgkin's disease treated with exclusive mantle radiation therapy.

Between January 1972 and December 1982 60 patients with pathological stage IA and IIA Hodgkin's disease (HD) were submitted to Mantle irradiation only. Twenty-five were in stage I (32.1%) and 35 in stage II (67.9%). All patients were submitted to staging laparotomy. Cases with large mediastinal mass were excluded from this series. Delivered doses were 44 Gy in involved areas, 40 Gy on the mediastinum and 36 Gy on uninvolved sites. Twenty-four patients in stage I (96%) and 33 in stage II (94.2%) obtained complete remission. Actuarial 10- and 20-yr overall (OS) rates were 86% and 79.1%, respectively. Event-free (EFS) and relapse-free (RFS) survival rates at 10 and 20 yr were 67.5% and 62.1%, respectively. The occurrence of disease relapse resulted in the only statistical significant prognostic factor for OS in both univariate and multivariate analysis. Distant and extranodal recurrences were significantly (P<0.01) related to a reduced OS. On multivariate analysis stage was the only determinant factor for increased RFS. Extended field RT proved to be an effective curative modality for stage I HD patients, whereas 15 out of 33 patients in stage II relapsed requiring salvage therapy. Long-term analysis of survival and treatment-related morbidity rates will improve our knowledge and assist the physicians to choose the therapeutic option to offer to HD patients.     

Gemcitabine and vinorelbine combination is effective in both as a salvage and mobilization regimen in relapsed or refractory Hodgkin lymphoma prior to ASCT

We investigated the efficacy of gemcitabine and vinorelbine (Gem/Vin) combination chemotherapy as a salvage and mobilization regimen in relapsed or refractory Hodgkin lymphoma (HL) patients prior to autologous hematopoietic stem cell transplantation. We retrospectively reviewed the data of our relapsed or primary refractory HL patients treated with Gem/Vin regimen which consisted of gemcitabine 1,000 mg/m²/day and vinorelbine 30 mg/m²/day on days 1, 8, and 15 every 28 days. The overall response rate was 72.4%. Ten (34.5%) patients achieved complete remission, 11 (37.9%) partial remission, and eight (27.6%) patients had no response. Mobilization with Gem/Vin regimen was successful in 20/23 (87%) patients while mobilization failure was seen in three (13%) patients. Gemcitabine and vinorelbine is an effective salvage regimen with acceptable toxicity and high mobilization potential in relapsed or refractory HL patients.     

Etoposide, mitoxantrone and prednisone: a salvage regimen with low toxicity for refractory or relapsed non-Hodgkin's lymphoma

BACKGROUND AND OBJECTIVES: Relapsed non-Hodgkin's lymphoma (NHL) is preferably treated with high-dose therapy and stem cell support. However, not all patients qualify for intensive chemotherapy. We evaluated the efficacy and toxicity of a new salvage chemotherapy regimen designed for patients with relapsed or refractory NHL who are not appropriate candidates for high-dose therapy (HDT). DESIGN AND METHODS: Seventy-nine patients received a regimen consisting of etoposide (350 mg/m(2) i.v. day 1), mitoxantrone (14 mg/m(2) i.v. day 1) and prednisone (80 mg/m(2) p.o. days 1-5) (EMP). The majority had aggressive NHL. Twenty-one patients were elderly, i.e. >60 years of age; RESULTS. The overall response rate in the 79 patients was 38% as compared to 67% in the elderly. The progression-free survival was 54% and 30% at 12 months and 24 months, respectively. The toxicity of the regimen was relatively low. No toxic deaths have occurred. In 28 of 231 cycles (12%) a CTC-grade 2-4 infection was encountered. Twenty-one hospital admissions were necessary because of infection or fever. Other toxicity was rare. Toxicity was not greater in the elderly patients. WHO performance status 2-4 and elevated serum lactate dehydrogenase (LDH) concentrationv were adverse prognostic factors for response as well as for overall survival. Another adverse prognostic factor for response was age <60 years. INTERPRETATION AND CONCLUSIONS: EMP is a new salvage regimen with a relatively low toxicity. It should be considered for patients with relapsed or refractory NHL who are not candidates for standard reinduction therapy and stem cell transplantation.