Mini-beam as salvage chemotherapy for refractory Hodgkin's disease and non-Hodgkin's lymphoma

Long-term disease-free survival after conventional dose salvage chemotherapy for relapsed or refractory non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) is rare. Intensive chemotherapy and autologous bone marrow transplantation (ABMT) is regarded by many as the treatment of choice. For lymphoma, eligibility for transplant is frequently restricted to cases with chemotherapy-sensitive disease or minimal tumour bulk. We evaluated the mini-BEAM regimen as further treatment for patients unresponsive to initial salvage therapy and thus ineligible for ABMT at our centre. Carmustine 60 mg/m(2) I.V. day one, etoposide 75 mg/m(2) I.V. days 2-5, cytosine arabinoside 100 mg/m(2) I.V. q12h days 2-5 and melphalan 30 mg/m(2) day 6 (mini-BEAM) was administered to 24 patients with lymphoma, 22 of whom were refractory to at least first-line salvage chemotherapy. Eleven had HD and 13 NHL. The complete response (CR) rate was 21% and the overall response was 59%. Febrile neutropenia occurred in 48% of treatment episodes. There were two treatment-related deaths. Thirteen patients underwent bone marrow transplantation (BMT), 11 received ABMT (8 HD, 3 NHL). Six patients did not achieve remission after transplant but 7 patients remain in continuous CR, with a follow-up of 6-17 months post-transplant. Consequently, 7 of 24 (29%) patients responded to mini-BEAM and many achieve long-term disease-free survival after BMT. Further evaluation of mini-BEAM as a salvage regimen prior to BMT is indicated.     

Activity of single agent vinorelbine in pretreated non-Hodgkin's lymphoma

BACKGROUND:: To assess the activity of single agent vinorelbine in pretreatednon Hodgkin's lymphoma. PATIENTS AND METHODS:: Twenty-three pretreated patients with non-Hodglun's lymphoma(14 intermediate-high grade, nine low-grade) were treated withvinorelbine 30 mg/m²/week for six months or up to four dosesafter achieving CR. RESULTS:: Among 13 evaluable patients with intermediatehigh grade lymphoma,three obtained CR and three PR, for an overall response rateof 46% (95% CI: 19%–75%). Median duration of responsewas six months. Othervise vinorelbine did not show any significantactivity in chemotherapy-refractory low-grade non-Hodgkin'slymphoma. Toxicity was acceptable, and the drug was well-toleratedeven in elderly patients. CONCLUSIONS:: The good activity and tolerability of vinorelbine in relapsedintermediate-high grade lymphoma suggest its inclusion in first-lineregimens, expecially in elderly patients. non-godgkin's lymphoma, salvage therapy, vinorelbine     

Short-term weekly chemotherapy followed by high-dose therapy with autologous bone marrow transplantation for lymphoblastic and Burkitt's lymphomas in adult patients

Background: Type and duration of treatment for highly aggressivenon-Hodgkin's lymphoma has been a matter of debate over thepast decade. To determine the therapeutic efficacy of an abbreviatedtreatment regimen, 26 patients with newly-diagnosed highly aggressivelymphomas, 17 of them belonging to the International WorkingFormulation (IWF) group I and 9 with Burkitt's lymphoma (IWFJ), were entered in a study using short-term weekly chemotherapyfollowed by high-dose therapy and autologous bone marrow transplantation.Patients and methods: Besides histology, requirements for entryinto to the study were age between 16 and 60 years, stage Ibulky disease and elevated LDH or stage II to IV disease withor without bulk or elevated LDH, and an absence of HTV infectionor CNS involvement at diagnosis. The treatment plan was 12 weeksof MACOP-B or VACOP-B chemotherapy followed by high dose therapyand autologous bone marrow transplantation in first completeremission. Results: Twenty patients (76%), 16 (62%) of thoseon MACOP-B or VACOP-B, 1 who had received 2 cycles of ProMACE-CytaBOMprior to MACOP-B and 3 after a first salvage reigmen, achievedcomplete remissions. Seventeen patients (65%) were transplantedin first remission, and 15 (58%) after induction treatment withonly MACOP-B or VACOP-B. Reasons for not being given high dosetherapy and autologous bone marrow transplantation (ABMT) werefailure to achieve complete remission in 6 patients, early relapsein 2 and severe pulmonary toxicity associated with chemotherapyin 1. The median time of follow-up was 45 months. At 3 years,the estimated event-free survival was 31% (CI 14%–50%)and the overall survival 48% (CI 25%–67%). There wereno deaths from toxic effects of treatment. Pretreatment factorsassociated with relapse were stage III or IV disease, age over30 years and bone marrow involvement. Logrank analysis showedthat age was the only factor significantly associated with poorevent-free survival. Conclusion: Short-term weekly chemotherapyfollowed by high-dose therapy with the CBV regimen in firstremission is not a highly effective treatment for advanced lymphoblasticand Burkitt's lymphomas. The 30% rate of failure to achievepartial remission after 6 weeks and/or complete response after12 weeks of MACOP-B or VACOP-B treatment, as well as the 42%failure rate to undergo ABMT in first remission, suggest thatmore aggressive chemotherapy should be used in the beginning. lymphoblastic lymphoma, Burkitt's lymphoma, VACOP-B, MACOP-B, ABMT, first remission     

Outcome of Patients with Relapsed or Refractory Non-Hodgkin's Lymphoma Referred for Autologous Bone Marrow Transplantation

Fifty-one patients with relapsed or refractory intermediate- or high-grade non-Hodgkin's lymphoma were referred for autologous bone marrow transplantation (ABMT). The primary criterion for eligibility was sensitivity to conventional-dose salvage chemotherapy. Of 47 patients who received salvage chemotherapy, 30 demonstrated chemotherapy-sensitive disease. Six eligible patients did not undergo ABMT for various reasons. A total of 24 patients underwent ABMT, with etoposide, melphalan ± total body irradiation as the intensive therapy regimen. There was one early treatment-related death and three non-responders. Of the remaining patients, 9 relapsed, while 11 remain in continuous complete remission (CR) at a median follow-up of 21 months after transplant (range 5-37 months). Two patients with chemosensitive disease and bone marrow involvement underwent allogeneic BMT with marrow from HLA-identical siblings. Both are in continuous CR at 6 and 12 months follow-up. Of the 25 patients who did not undergo ABMT, all have died (median survival 5 months).

The results indicate that approximately one-half of relapsed or refractory aggressive histology lymphoma patients referred for ABMT eventually undergo transplantation, if chemotherapy-sensitive relapse is the major criterion for eligibility. Approximately 25% of the referred patients may become long-term disease-free survivors with this approach. Reports of marrow transplant series should include all patients referred for ABMT as the denominator for calculating disease-free survival in order to reduce the bias of patient selection.     

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     

Salvage chemotherapy with mini-BEAM for relapsed or refractory non-Hodgkin's lymphoma prior to autologous bone marrow transplantation

Background: The role of intensive chemotherapy with autologous blood andmarrow transplantation (ABMT) for patients with relapsed or refractoryintermediate grade non-Hodgkins lymphoma has recently been established.However, conventional dose salvage chemotherapy is frequently used todetermine chemotherapy sensitivity and reduce tumor bulk prior to intensivetherapy. Different salvage regimens have been proposed but none appearssignificantly superior. The purpose of this study was to determine theefficacy of mini-BEAM salvage chemotherapy in patients referred for ABMT andto define prognostic factors of response.Patients and methods: One hundred four patients referred forconsideration of ABMT after failure of primary anthracycline-basedchemotherapy received BCNU 60 mg/m² day 1, etoposide 75mg/m² day 2–5, ara-C 100 mg/m² q12h day2–5, melphalan 30 mg/m² day 6 (mini-BEAM) until maximumtumor reduction. Median age was 52 (range 18–65); 57% had failedto achieve a complete response (CR) to doxorubicin-based chemotherapy atdiagnosis and only 13% had a previous CR lasting > 12 months.Seventy-six received mini-BEAM as first salvage chemotherapy.Results: The overall response rate (RR) was 37% (95%confidence interval (CI) 28–46%) with 12 patients achieving CRand 25 achieving PR. Theresponse rate among patients treated as first salvage was 43% comparedto 20% for patients who had failed to respond to a previous salvageregimen. Only 15% of patients who failed to respond to mini-BEAMresponded to another conventional dose salvage regimen. Thirty-eight of 104patients ultimately demonstrated sufficient response to proceed to ABMT.Actuarial survival at four years is 22% for all 104 patients, and36% for those who went on to ABMT. For those who were not transplanted,four-year survival was 18%. B symptoms and tumor burden at relapse weresignificant predictors of response to mini-BEAM in multivariate analysis, andidentified a poor prognosis group of patients unlikely to be cured by thisapproach.Conclusions: Mini-BEAM does not appear to be a superior salvage regimen inthis high-risk group of relapsed or refractory NHL patients for whom ABMT wasthe ultimate treatment intention. Only one-third of patients referred for ABMTultimately proceed to transplant; alternative treatment strategies should bedeveloped for those with a low likelihood of cure by this approach.     

Risk of new primaries after chemotherapy and/or tamoxifen treatment for early breast cancer

BACKGROUND:: Both chemotherapy and tamoxifen are widely used either aloneor in combination as adjuvant treatment following mastectomy.Despite the fact that both of them exhibit carcinogenic propertiesin experimental models, detailed reports on the incidence ofnew primaries following chemotherapy and/or tamoxifen in patientswith early breast cancer are limited. PURPOSE:: To investigate the incidence of new primaries (including oppositebreast tumors and skin cancers) in untreated patients and inpatients treated with either tamoxifen or chemotherapy or withboth modalities. PATIENTS AND METHODS:: A total of 1696 patients with early breast cancer, 1286 of whomwere treated with either CMF-based adjuvant chemotherapy (n= 410), tamoxifen (n = 656) or with a combination of the two(n = 220) were considered for the present analysis. Patientswere operated on between November 1983 and December 1991 andwere followed up to June 1994. Detailed information about secondmalignancies were available for all patients. RESULTS:: Overall, 53 new primaries, 19 of them opposite breast tumors,occurred in 53 patients. The actuarial cumulative incidencerates at 5 years were: 3.1% (95% CI: 1.4%– 4.8%) in untreatedpatients; 1.7% (95% CI: 0.0%–3.5%) in tamoxifen-treatedpatients; 4.2% (95% CI: 1.3%–7.1%) in chemotherapy-treatedpatients and 2.6% (95% CI: 0.0%%5.2%) in the chemo-tamoxifengroup (all groups: P = n.s.; chemotherapy-treated versus tamoxifen-treated:P = 0.01). The corresponding figures, after exclusion of thepatients with opposite-breast and skin tumors, were: untreatedpatients: 2% (95% CI: 0.6%–3.4%); tamoxifen-treated patients0.95% (95% CI: 0.0%–2.4%); chemotherapy-treated patients:2.6% (95% CI: 0.4%–4.8%); chemotherapy plus tamoxifen:1.65% (95% CI: 0.4%–3.8%); (all groups: P = n.s.; CT versusTAM P = 0.05). Chemotherapy-treated patients showed a risk thatwas about two-fold that of the one to be expected in the generalpopulation. By contrast, a decrease in the total risk was observedin patients treated with tamoxifen. Patients who received chemotherapyand tamoxifen as well as those in the no-treatment group showeda risk which was comparable to that of the general population. CONCLUSIONS:: Adjuvant chemotherapy appears to increase the risk of secondmalignancies. By contrast, tamoxifen seems to exert an overallprotective effect in this regard, and it also appears to counteract,at least partially, the carcinogenic effect of chemotherapy. IMPLICATIONS:: While there is plenty of evidence that the benefit achievedby adjuvant chemotherapy considerably exceeds the risk of secondmalignancies, the indiscriminate use of chemotherapy shouldbe avoided, particularly in patients with a low risk of relapse.Moreover, it seems reasonable to prefer tamoxifen over chemotherapyfor patients likely to obtain comparable therapeutic benefitfrom antiestrogenic treatment. adjuvant chemotherapy, adjuvant tamoxifen, adjuvant chemo-tamoxifen therapy, early breast cancer, second malignancies     

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.     

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

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

Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors.

PURPOSE: The efficacy of paclitaxel was evaluated in combination with ifosfamide and cisplatin as second-line chemotherapy for patients with relapsed testicular germ cell tumors (GCTs). PATIENTS AND METHODS: Forty-six patients with progressive metastatic GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. Eligibility required that patients have both a testis primary tumor site and a prior complete response (CR) to a first-line chemotherapy program, which had been identified previously as favorable prognostic factors to conventional-dose salvage chemotherapy. RESULTS: Thirty-two (70%) of 46 patients achieved a CR to treatment. Three patients (7%) who achieved a CR relapsed after TIP chemotherapy. Twenty-nine patients are continuously disease free at a median follow-up time of 69 months, resulting in a 63% durable CR rate and a 2-year progression-free survival rate of 65% (95% CI, 51% to 79%). CONCLUSION: Four cycles of TIP as second-line therapy achieved a durable CR rate in a high proportion of patients with relapsed testicular GCT. The high CR rate emphasizes the importance of patient selection according to prognostic factors to achieve a favorable outcome to conventional-dose salvage therapy.     

A Single-Center Study of 11 Patients with Intraocular Lymphoma Treated with Conventional Chemotherapy Followed by High-Dose Chemotherapy and Autologous Bone Marrow Transplantation in 5 Cases

Intraocular lymphoma (IOL) is a rare form of non Hodgkin lymphoma (NHL); it has a poor prognosis and is frequently associated with central nervous system (CNS) infiltration. We report the results of a prospective study of 11 patients with IOL who received conventional chemotherapy (CT), followed by salvage high-dose (HD) CT with autologous bone marrow transplantation (ABMT) in five cases. All 11 patients had abnormal funduscopic findings and six had CNS involvement at diagnosis. The diagnosis was based on vitrectomy in 10 cases and cerebral stereotaxic biopsy in one. Pathologic studies showed large-cell NHL in all cases. These large-cell NHL were of the B-cell type in 8 cases and of the T-cell type in two. First-line therapy consisted of a combination of cisplatin 25 mg/m² as a 24-hour IV infusion on 4 consecutive days, VP-16 40 mg/m2 for 4 days, aracytine 2 g/m² IV on day 5, and methylprednisolone 500 mg IV daily for 5 days (ESHAP) in 5 cases; alternating courses of ESHAP and HD methotrexate (MTX) in 4 cases; and HD MTX in 2 cases. Three patients underwent ocular and whole-brain radiation therapy. Five refractory patients subsequently received intensive CT with thiotepa 750 mg/m2, busulfan 10 mg/kg and cyclophosphamide 120 mg/kg, followed by ABMT.

First-line treatment failed in 10 evaluable cases. One patient died of CNS progression at 12 months. All the patients who underwent intensive CT and ABMT entered CR; two relapsed at 6 months and three are alive in CR 15, 15 and 14 months after ABMT. Six patients are alive with persistent disease at 8, 13, 14, 15, 18 and 24 months. It seems in conclusion that, high-dose thiotepa, busulfan and cyclophosphamide followed by ABMT is effective in some cases of refractory IOL.     

Methyl-Gag, Ifosfamide, Methotrexate and Etoposide (Mime) as Salvage Therapy for Non-Hodgkin's Lymphomasa Swedish national prospective study

One hundred and two patients with recurrent or refractory non-Hodgkin's lymphoma (NHL) were treated with MIME (methyl-GAG, ifosfamide, methotrexate, etoposide) in accordance with a prospective protocol. Of 75 patients with high-grade malignant NHL (median age 57 years, range 21-79), 15 patients (20%) obtained a complete response (CR) and 27 patients (36%) a partial remission (PR), giving an overall response rate of 56%. The remissions were usually short when not consolidated with ABMT or radiotherapy. The probability of progression-free survival after 2 years was 13%, and the cause-specific survival was 23%. Of 27 patients with low-grade NHL (median age 46 years, range 37-86), 7% had a CR and 37% a PR giving a response rate of 44%. The remissions were again usually short when not consolidated, and the probability of progression-free survival at two years was 11%, and the cause-specific survival 26%. The main toxicity was hematological with septicemia in 20% of the patients and other severe infections in 19%. Fifteen patients (11 high-grade NHL and 4 low-grade NHL) were consolidated with high-dose therapy followed by ABMT, of whom 6 are in continuous CR. We conclude that MIME can induce remissions in NHL patients, and that the remission rates are comparable with those of many other salvage regimens. The remissions are, however, generally of short duration and need consolidation. There was considerable toxicity therefore patients not suitable for ABMT preferably should be treated with less toxic salvage regimens.     

自体骨髓移植治疗淋巴瘤的时机选择

本文报告用自体骨髓移植治疗11例晚期淋巴瘤,获得了良好效果。作者和文献认为,自体骨髓移植不仅是一种有效手段,而且有广泛的适应症。不失时机地用自体骨髓移植治疗淋巴瘤,可使部分晚期病例,获得长期缓解。     

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.     

Intensive cytoreductive therapy followed by autologous bone marrow transplantation for patients with hematologic malignancies or solid tumors

Fifty patients were studied. Twenty patients with non-Hodgkin's lymphomas (NHL) of high-grade malignancy and 21 patients with acute leukemia (AL) were treated with high-dose cyclophosphamide and total body irradiation, and three patients with Hodgkin's disease (HD) and six patients with solid tumors were treated with high-dose cyclophosphamide and VP16-213. Those procedures were followed by autologous bone marrow transplantation (ABMT). All patients had received conventional chemo(radio)therapy before the ABMT procedure. Although remissions were obtained in patients with cytotoxic drug-resistant diseases (lymphomas and solid tumors), none has become a long-term survivor, as occurred also in patients with solid tumors in partial remission (PR). Two of five patients with NHL in PR at the time of ABMT have become long-term disease-free survivors (28+, 56+ months). Ten patients with NHL were treated in complete remission (CR) and seven are in unmaintained CR; four with long follow-up (14+ to 59+ months). All patients with AL were treated in CR; two patients received ABMT in second CR, and both relapsed. Ten of nineteen patients in first CR relapsed; eight are alive in CR, five with long follow-up. Four deaths were therapy-related, all were patients in poor clinical condition. Intensive cytoreductive therapy followed by ABMT can produce prolonged disease-free survival (and probably cure) in a fair number of patients with poor risk NHL in CR and PR and probably also in patients with acute myeloblastic leukemia in first CR. This procedure was not successful in achieving long-term disease-free survival in patients with refractory lymphomas or solid tumors.     

Salvage therapy with ProMACE-MOPP followed by intensive chemoradiotherapy and autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma who failed to respond to first-line CHOP.

PURPOSE: We used alternative chemotherapy immediately followed in early-response patients by high-dose chemoradiotherapy and autologous bone marrow transplantation (ABMT) to treat patients with non-Hodgkin's lymphoma (NHL) who had failed to respond to first-line chemotherapy. PATIENTS AND METHODS: Thirty-one patients with NHL of intermediate- or high-grade malignancy who had failed to respond to first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy were treated. Seventeen patients had primary refractory disease and 14 had relapsed from first complete response (CR). The treatment consisted of prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, mechlorethamine, vincristine, and procarbazine (ProMACE-MOPP) salvage chemotherapy, followed, in case of responsive disease (at least partial response [PR]), by high-dose cyclophosphamide and total-body irradiation (TBI) with ABMT. RESULTS: Twenty-eight of 31 (90%) patients achieved PR (23 patients) or CR (five patients) with ProMACE-MOPP, and three failed to respond. Seventeen of 28 (61%) patients who responded underwent the ABMT procedure, which resulted in CR in 14 patients (82%); three failed to respond. Eleven responsive patients were not transplanted because of residual bone marrow infiltration (five patients), patient refusal (four patients), and ProMACE-MOPP-related mortality (two patients). To date, nine patients are alive and in CR, seven with a median follow-up of 41 months (range, 17 to 84 months). Referring to the original CHOP treatment, five of 17 (29%) patients with primary refractory disease remain free of disease at a median of 36 months after ABMT, and four of 14 (29%) patients in first relapse remain free of disease at a median of 33 months after ABMT. One patient died of AMBT-related toxicity. CONCLUSION: ProMACE-MOPP salvage chemotherapy produces a high early-response rate in patients who fail to respond to first-line CHOP, and more than half of the responding patients can be scheduled to receive ABMT, resulting in disease-free survival (DFS) at 3 years in 50% of the transplanted patients and in 25% of the original number of patients intended to receive this treatment.     

Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin, cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation: Children's Cancer Group Study CCG-5912.

PURPOSE: To determine the toxicity and response rate in children treated with dexamethasone, etoposide, cisplatin, high-dose cytarabine, and L-asparaginase (DECAL) for recurrent non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). PATIENTS AND METHODS: Ninety-seven children with recurrent NHL (n = 68) or HD (n = 29) were enrolled. Treatment consisted of two cycles of DECAL, then bone marrow transplantation or up to four cycles of ifosfamide, mesna, and etoposide alternating with DECAL maintenance therapy. RESULTS: After two cycles of DECAL induction therapy, complete response (CR) or partial response (PR) was reported in 19 (65.5%; 10 CRs and nine PRs) of 29 patients with HD and 29 (41.6%; 23 CRs and six PRs) of 68 patients with NHL. When only 24 patients with HD and 58 patients with NHL who were assessable for response were considered, the response rates were 79.2% (19 of 24 patients) and 50.0% (29 of 58 patients), respectively. Five-year event-free survival was 26% +/- 9% and 23% +/- 5% in patients with HD and NHL, respectively. Five-year survival was 31% +/- 14% and 30% +/- 6%, respectively. Although median time to treatment failure was significantly longer in patients with HD (EFS, P =.002; survival, P =.011), this difference did not translate into a higher long-term survival. Grade 3 or 4 toxic effects were observed during induction in 70 (72%) of 97 patients and during maintenance in 45 (70%) of 64 courses of DECAL therapy. Pancytopenia and systemic infections in particular were frequently observed. Other toxic effects were uncommon. Although not a formal part of the therapy or the study design, 42 patients who responded to therapy who underwent bone marrow transplant did not show any benefit from this approach. CONCLUSION: DECAL is an effective and tolerable salvage regimen for treating patients with recurrent NHL and HD.     

High-dose chemotherapy with autologous stem cell support in first-line treatment of aggressive non-Hodgkin lymphoma - results of a comprehensive meta-analysis

BACKGROUND: Randomized controlled trials (RCTs) reported conflicting results on the impact of high-dose chemotherapy (HDCT) and autologous stem cell transplantation in the first-line treatment of patients with aggressive non-Hodgkin lymphoma (NHL). METHODS: We performed a systematic meta-analysis to assess the efficacy HDCT compared to conventional chemotherapy in aggressive NHL patients with regard to complete response (CR), overall survival (OS), event-free survival (EFS), toxicity, and impact of the age-adjusted International Prognostic Index (aaIPI) risk factors. We searched the Cochrane Library, MEDLINE and other databases (1/1990 to 1/2005). Hazard ratio (HR), relative risks (RR) and 95% confidence intervals (CIs) were calculated using the fixed effect model. RESULTS: Fifteen RCTs including 2728 patients were identified. HDCT improved CR when compared to conventional chemotherapy (RR 1.11, CI 1.04-1.18). Overall, there was no evidence for HDCT to improve OS (HR 1.05, 95% CI 0.92-1.19) or EFS (HR 0.92, 95% CI 0.80-1.05) when compared with conventional chemotherapy. However, subgroup analysis indicated OS differences (p=0.032) between good (HR 1.46, 95% CI 1.02-2.09) and poor risk (HR 0.95, 95% CI 0.81-1.11) patients. Conflicting results were reported for poor risk patients, where some studies reported improved and others reduced OS and EFS after HDCT. CONCLUSION: There was no evidence that HDCT improved OS and EFS in good risk NHL patients. The evidence for poor risk patients is inconclusive. HDCT should not be further investigated in good risk patients with aggressive NHL but high quality studies in poor risk patients are warranted.     

The incidence of lymphoma in first-degree relatives of patients with Hodgkin disease and non-Hodgkin lymphoma: results and limitations of a registry-linked study

BACKGROUND: The precise incidence of familial Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) in first-degree relatives is unknown. Through record linkage using two population-based sources, the authors estimated the risk of HD and NHL in family members of lymphoma probands. METHODS: The authors identified 8,037 first-degree relatives of 2,606 lymphoma cases (28.5% HD, 71.5% NHL) treated between 1970 and 1993 in 3 hospitals in Israel via the family file of the Population Registry. The authors linked this file with the Israel Cancer Registry, then calculated the standardized incidence ratio (SIR) by dividing the observed number of cases with the expected, adjusting for age, gender, calendar year, and continent of origin. RESULTS: The family file yielded incomplete ascertainment of relatives (for 771 probands, no relatives were identified). Twenty cases of lymphoma--6 HD and 14 NHL--were identified among relatives of lymphoma patients. The SIR for HD was 1.15 (95% confidence interval [CI]: 0.42-2.51) and for NHL 1.71 (95% CI: 0.93-2.87), considering the entire population of first-degree relatives. SIRs among siblings of lymphoma probands were 3.12 (95% CI: 1.01-7.29) for HD, 2.16 (95% CI: 0.45-6.31) for NHL, and 2.68 (95% CI: 1.15-5.27) for all lymphomas. There were 4 HD/HD, 1 NHL/NHL, and 3 NHL/HD sibling pairs. For HD/HD and NHL/NHL sibling pairs, the interval between lymphoma occurrence in proband and sibling was 1-4 years, whereas for HD/NHL pairs this ranged from 16 to 21 years. CONCLUSIONS: The risk of lymphoma among siblings of lymphoma probands was over 2.5-fold that of the general population and lower among other family members. The temporal proximity of HD/HD and NHL/NHL sibling pairs argues for environmental as well as genetic etiology. This method was hampered by incomplete data.     

Incidence of Post Transplant Myelodysplasia/Acute Leukemia in Non-Hodgkin's Lymphoma Patients Compared with Hodgkin's Disease Patients Undergoing Autologous Transplantation Following Cyclophosphamide, Carmustine, and Etoposide (CBV)

Secondary malignancies, particularly myelodysplasia (MDS), are serious events following high dose therapy with autologous stem cell support. We observed a higher frequency of secondary malignancies in patients with Hodgkin's disease (HD) than in patients with non-Hodgkin's lymphoma (NHL) undergoing high dose therapy with the same non-TBI conditioning regimen. Three hundred patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) were treated with Cyclophosphamide, carmustine and etoposide and autologous stem cell support from 1986 through 1994. Median follow up of survivors is 3.9 years. Five-year survival is 51 % for HD and 48 % for NHL. Eleven patients developed second malignancies (9/150 treated for HD vs. 2/150 treated for NHL) a median of 2.4 years from transplantation and 5.2 years from initial diagnosis. Six patients had myelodysplasia or acute leukemia (MDS/AML) and 5 had lymphomas or solid tumors. Actuarial risk of MDS/AML at five years for patients transplanted for non-Hodgkin's lymphoma is 3 % (95 % CI 0.6-9.6%). HD patients had significantly different pretreatment characteristics than patients with NHL. A Cox model showed that greater number of prior relapses and prior radiation therapy were significant risk factors for the development of MDS/AML. These data suggest that Cβ V is associated with a lower risk of secondary MDS/AML than TBI containing regimens and that much of the risk is associated with the pre-transplantation therapy. The use of autotransplantation early in the course of therapy for relapsed lymphoma might prevent some cases of MDS/AML.