Chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin for parenchymal brain lymphoma.

Ten patients with parenchymal CNS lymphoma received combination chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin (DHAP), and additional therapy according to clinical circumstances. Two of four patients with primary CNS lymphoma achieved and remain in complete remission (CR). Four of six patients with CNS lymphoma at relapse also achieved CR. DHAP is active against CNS lymphoma. Further trials with DHAP, particularly in conjunction with other treatment modalities, are warranted.

Frequent nonrandom chromosome abnormalities in 27 patients with untreated large cell lymphoma and immunoblastic lymphoma.

Fresh tumor samples from 27 patients with large cell lymphoma, either previously untreated (26 patients) or minimally treated (one patient), were processed for cytogenetic studies. Cytogenetic abnormalities were observed in all patients, most commonly in chromosomes 1, 3, 7, 12, 14, 17, and 18. Nine chromosomal breakpoints appeared frequently: 14q32 in 14 instances; 18q21 in seven; 9p13-21, 17p11-13, and 3q21-23 in six each; 1p11-21 in five instances; 1p36 in four; and 2p21-23 in three. The most common structural abnormalities were t(14;18)(q32;q21) in seven patients (26%) and 17p- in six (22%). The presence of 17p- was associated with a significantly higher proliferative capacity as manifested by the percentage of S phase = 22% versus 11% for cases without 17p-(P less than 0.05). Trisomy 12, typical of small lymphocytic lymphoma, was seen in five patients in this series, all of whom had diffuse large cell lymphoma; frequently, it appeared simultaneously with t(14;18). The two patients with immunoblastic lymphoma of B-cell type had an abnormality involving chromosome 2p21-23. Deletions in the long arm of chromosome 6, previously described as typical of diffuse large cell lymphoma and B-cell immunoblastic lymphoma were observed infrequently in this series. However, this abnormality has been present in 50% of patients with large cell lymphoma previously exposed to therapy, suggesting that it may be related to effects of chemotherapy or to clonal evolution.

Long-term follow-up with ABDIC salvage chemotherapy of MOPP-resistant Hodgkin's disease.

Thirty-six consecutive patients with advanced recurrent Hodgkin's disease resistant to chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) were treated with doxorubicin (Adriamycin), bleomycin, (dacarbazine) DTIC, (lomustine) CCNU, and prednisone (ABDIC). Among the 34 patients evaluable for response, complete remission occurred in 35% and partial remission in 35%. The achievement of complete remission during primary MOPP induction was a statistically significant prognostic factor that predicted complete remission with ABDIC (p less than 0.01). The median time to complete remission was 2 months (range 1-11 mo). The median relapse-free survival time for complete responders is 47 months, and an estimated 53% of all patients who achieve complete remission are projected to be alive, free of disease off therapy at 3 years from initiation of ABDIC. The median survival of all patients is 24 months. The median survival of complete responders, partial responders, and nonresponders is 70, 17, and 4 months, respectively. The survival curve for complete responders is significantly different from that for partial responders (p less than 0.01); the survival curve for partial responders is also significantly different from that of nonresponders (p less than 0.01). Toxicity of ABDIC was acceptable; only one patient died from complications of myelosuppression. Our results indicate that ABDIC is a potentially curative regimen for a fraction of patients with MOPP-resistant Hodgkin's disease who achieve complete remission with prior MOPP therapy. It also prolongs the survival of patients who do not achieve complete remission with prior MOPP therapy.

Stomach conservation in stages IE and IIE gastric non-Hodgkin's lymphoma.

Thirty-four patients with stages IE and IIE gastric lymphoma were treated with chemotherapy and radiotherapy combinations without stomach resection. In 20 patients, the diagnosis was established by endoscopic biopsy only; the other 14 had laparotomy and biopsy. No patient had a gastrectomy before treatment. Nineteen patients had stage IE disease and 15 had stage IIE. Lymphoma diagnoses were: diffuse large-cell, 26; immunoblastic, three; diffuse well-differentiated, three; nodular mixed, one; and unclassified, one. The treatment plan was to deliver an initial four cycles of chemotherapy, followed by radiotherapy, and finally, more chemotherapy. Thirty-three patients received cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo). Four patients with stage IIE disease received cyclophosphamide, methotrexate, etoposide, and dexamethasone (CMED). Twenty-three patients (68%) never had a relapse. Three patients had successful salvage therapy, one for local recurrence and two for tumor dissemination. Five patients died of recurrent abdominal disease, and one died of tumor dissemination. Two died of treatment-related complications, one of sepsis during treatment with CMED and one of bleomycin-induced lung fibrosis. No patient developed stomach perforation or bleeding as a result of chemotherapy or radiotherapy. Twenty-four of the 26 surviving patients were able to retain their stomachs. One patient required a gastrectomy for progressive disease during chemotherapy, and another required a subtotal gastrectomy for relief of an obstruction caused by cicatrization. These data show that surgery is not a necessary procedure in gastric lymphoma. Favorable results can be achieved by combining effective chemotherapy and local radiation.

Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma.

Based on remarkable activity in refractory lymphomas, a combination of etoposide, cisplatin (both administered by 4-day continuous infusions), cytarabine (Ara-C), and dexamethasone (EDAP) was evaluated in 20 patients with advanced myeloma refractory to standard melphalan and prednisone (MP) and/or vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dexamethasone (VAD) and even to high doses of melphalan (HDM) (seven patients). Forty percent of patients responded regardless of previously recognized risk factors (eg, duration of drug resistance, tumor mass, and serum lactic dehydrogenase [LDH] level). While the median survival was only 4.5 months, patients with good performance (Zubrod less than 2) and low or intermediate tumor stage survived more than 14 months compared with only 2 months for the remaining group. EDAP could be readily administered in the outpatient clinic, but neutropenic fever prompted hospital admission in 80% of patients, half of whom developed penumonia and sepsis, a fatal outcome in four patients. Severe myelosuppression was of short duration, so that subsequent cycles could be administered every 3 to 4 weeks. No serious extramedullary toxicity, including renal toxicity, was encountered. Marrow toxicity and hence infectious complications may be reduced by elimination of Ara-C without compromising treatment efficacy. We conclude that the lack of cross-resistance with VAD and even HDM makes EDAP or a similar combination an attractive regiment to be formally explored in an alternating sequence with VAD in high-risk myeloma.

Results of MIME salvage regimen for recurrent or refractory lymphoma.

Based on encouraging results of two previous ifosfamide-VP-16 salvage combinations, methyl-gag was added to ifosfamide, methotrexate, and etoposide (VP-16). This combination is called MIME. A total of 208 patients with recurrent lymphoma were treated with this regimen. Response rates were 24% for complete remission and 36% for partial remission. The MIME regimen was more effective in patients who were treated after being off front-line therapy for longer than 6 months. However, responses were also seen in patients with disease clearly resistant to front-line therapy, suggesting that MIME was at least partially non-cross-resistant with front-line doxorubicin-containing regimens. The 15-month median relapse-free survival of complete responders and the 9-month overall median survival time for all patients treated were both similar to results from previous ifosfamide-VP-16 combination use. This regimen has been effective in the treatment of patients with recurrent or refractory lymphoma, but cannot be considered curative in the majority of cases.

Stage IV diffuse large-cell lymphoma: a long-term analysis.

A long-term analysis of the clinical outcome of previously untreated adult patients who presented with stage IV diffuse large-cell lymphoma at diagnosis was performed to identify possible prognostic factors. Sixty-one patients were seen between 1974 and 1981; all were treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin followed by cyclophosphamide, vincristine, prednisone, and bleomycin for a total of one year. Overall five-year survival was 48.5%, with a median follow-up of 53 months. Of the 56 patients evaluable for remission status, 41 achieved a complete remission, and 27 are alive and disease free. Clinical factors of prognostic importance for survival included age, constitutional symptoms, lactate dehydrogenase (LDH) level, presence of mediastinal disease, large-cell infiltration of bone marrow, and number of extranodal sites of disease. The proportional hazards model then identified age, number of extranodal sites, and, to a lesser extent, serum LDH level as independent risk factors for survival. Four distinct patient risk groups were identified using these three factors. Younger patients with only one extranodal site of disease and normal LDH levels responded well on this therapy, with 100% alive at five years. In contrast, survival was less than 30% at five years for patients in the lowest risk group. There were 11 relapses; LDH level, constitutional symptoms, and mediastinal disease predicted for relapse. Knowledge of these risk factors permits individualization of treatment planning and allows more meaningful comparisons with the results of treatment studies using other intensive regimens.

MIME chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide) as treatment for recurrent Hodgkin's disease.

Forty-seven patients with Hodgkin's disease in relapse were treated with MIME combination chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide). All patients had previously received nitrogen mustard, vincristine, prednisone, procarbazine (MOPP) or similar regimens and doxorubicin-containing combinations, and many had received extensive irradiation. Complete remission (CR) occurred in 23%, and was influenced by presence of extranodal disease, hemoglobin, lactic dehydrogenase (LDH), and number of prior relapses. Median survival for all patients was 50 weeks, and was affected adversely by the presence of extranodal disease and the number of prior relapses. Toxicity was significant, including infections (23%), neutropenic fever (34%), and hemorrhagic cystitis (23%), but was related in part to the extent of prior therapy. These results with this novel chemotherapy program in heavily pretreated patients suggest that MIME should be studied in less extensively treated patients and considered as a part of treatment programs for patients with Hodgkin's disease in first relapse.

High-dose cytosine arabinoside in non-Hodgkin's lymphoma.

Thirty-two patients with refractory non-Hodgkin's lymphoma were treated with high-dose cytosine arabinoside (ara-C) given at 2 g/m2 IV over three hours every 12 hours for 4-8 g/m2/course repeated at three to four week intervals. There were eight partial responses (29%) and two minor responses among 28 evaluable patients. The median response duration was 10 weeks (range, 6-33 weeks). The median survival was significantly prolonged in responders compared to nonresponders (28 versus 15 weeks; p = 0.03). Two additional patients treated with 12 g/m2/course died of sepsis and myelosuppression. The dose-limiting toxicity was myelosuppression, which was more pronounced in patients with prior extensive radiation therapy and bone marrow involvement. In vivo measurements of intracellular concentrations of ara-CTP, the active metabolite of ara-C, showed significantly higher values in bone marrows with lymphomatous involvement compared to normal bone marrows (210 versus 95 microM; p = 0.05), probably indicating a preferential formation and retention of ara-CTP in malignant cells compared to normal hemopoietic cells. In addition, higher ara-CTP levels were found in bone marrows that had higher percentages of cells in S phase.

Multivariate analysis of prognostic factors in stage IV follicular low-grade lymphoma: a risk model.

We analyzed the records of 96 previously untreated patients with stage IV follicular low-grade lymphoma (FLGL) uniformly treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo) chemotherapy from 1972 to 1982. The overall complete remission (CR) rate was 77%. At a median follow-up of 138 months, the 10-year cause-specific survival rate was 42% with a median survival of 100 months. Failure-free survival (FFS) was 15% at 10 years with a median FFS of 30 months. Multivariate analysis showed peripheral lymph node size (LN), degree of marrow involvement, and sex, in that order, to be important for FFS, while the number of extranodal sites (#ENS), LN, sex, and degree of marrow involvement were important for cause-specific survival. We devised a tumor burden (TB) model, incorporating #ENS, LN, and degree of marrow involvement. Three groups were identified with statistically significant differences in cause-specific survival and FFS. Those with low TB (one ENS exclusive of extensive marrow and nodal disease less than 5 cm) had a 10-year cause-specific survival of 73% compared with 24% for patients with high TB (greater than or equal to two ENS and nodal disease greater than or equal to 5 cm) (P less than .001) and 40% for those with intermediate TB (either greater than or equal to 2 ENS, or extensive marrow only, or nodal disease greater than 5 cm) (P = .050). Patients with low TB had a 10-year FFS rate of 32%, while the intermediate and high TB groups had 10% and 9% FFS, respectively (P = .003). Because sex was a very strong prognostic variable, we created a risk model for survival and FFS based on TB and sex. Females with low TB had the best prognosis (92% survival and 50% FFS at 10 years) and males with high TB had the worst outlook (median survival and FFS, 43 and 12 months, respectively). Other TB-sex combinations defined two groups with statistically significant differences in survival but comparable FFS. This model should aid in the design and analysis of future trials.

Tumor burden assessment and its implication for a prognostic model in advanced diffuse large-cell lymphoma.

Previously untreated adult patients who presented with advanced diffuse large-cell lymphoma (DLCL) at diagnosis were studied to identify possible prognostic factors. One hundred five patients were seen between 1974 and 1981; 45 patients were stage III and 60 patients were stage IV. All patients received cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo). Stage III patients also received radiation therapy alternated with chemotherapy. Overall survival was 50% at 5 years and 43% at 8 years. Seventy-four patients achieved a complete remission (CR) and 37 are alive and disease-free with a median follow-up of 72 months. There was no difference in clinical outcome between stage III and stage IV. However, a proportional hazards model identified lactic dehydrogenase (LDH) level and tumor burden, among all clinical factors studied, as independent risk factors for survival. These two factors were also important for achievement of remission and relapse-free survival. Three distinct patient risk groups were identified with 5-year survival rates of 87%, 48%, and 20%, respectively. The measure of tumor burden proposed herein, along with LDH level, can be used for developing treatment programs, and for meaningful comparison of different treatment regimens, as well as assessment of prognosis.

Small noncleaved cell lymphoma in adults: superior results for stages I-III disease.

Small noncleaved cell lymphoma (SNCCL), a rare lymphoma in adults, is associated with not only a rapid complete response (CR) to chemotherapy but also with the potential to rapidly relapse both systemically and in the CNS. We treated 44 assessable adults with two similar protocols, consisting of three sequential chemotherapy combinations and intrathecal prophylaxis with methotrexate and cytarabine. The overall CR rate was 80%; it was 100% in patients with Ann Arbor (AA) stages I-III disease and 57% in those with stage IV disease. The overall survival (OS) rate at 5 years was 52%. The overall 5-year freedom from tumor mortality (FTM) rate was 63%; it was 95% for patients with AA stages I-III disease, and 29% for those with stage IV disease. Stepwise multivariate analysis of factors associated with remission duration and survival indicated that advanced-disease stage and age of 40 years or over were predictors of poor prognosis. Twelve patients with positive human immunodeficiency virus (HIV) serology were also included in this series. They had an 83% CR rate and an 83% 5-year FTM, but only a 36% 5-year OS; most deaths were secondary to opportunistic infection. Histologic subtype (Burkitt's lymphoma [BL] or non-Burkitt's lymphoma [NBL]) did not correlate with patient age, site of tumor presentation, response to therapy, or survival. Both protocols achieved comparable results. The approach used in these protocols is highly effective for patients with early staged disease, regardless of their HIV status; however, better therapy is necessary for those with SNCCL presenting in an advanced stage.

Prognostic factors for response and survival after high-dose cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation for relapsed Hodgkin's disease.

Sixty-one patients with relapsed Hodgkin's disease who had failed a mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)- and a doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-like regimen were treated with a high-dose combination chemotherapy containing cyclophosphamide, carmustine, and etoposide (CBV) and autologous bone marrow transplantation (ABMT). Fifty-nine patients were treated in relapse and two were intensified early in third remission. Following therapy, 29 patients (47%) were in complete remission (CR), 18 patients (30%) achieved a partial response (PR), and 14 patients (23%) had progressive disease (PD). Among the partial responders, six patients achieved a CR following addition of local radiation therapy to sites of residual nodal disease. For a minimum follow-up of 2 years, 23 patients (38%) are alive and free of disease. High-dose CBV therapy produced severe myelosuppression, and there were four (7%) treatment-related deaths. A multivariate analysis identified failure of more than two prior chemotherapy treatments and poor performance status as important adverse risk factors for survival. Patients who had no adverse risk factor and/or were intensified with CBV while Hodgkin's disease was still responding to conventional chemotherapy, had a CR rate of 63%, with 77% projected 3-year survival; whereas, all other patients had a CR rate of 31%, and a projected 3-year survival of only 18%. Our results demonstrated that CBV and ABMT can induce remission duration of 2 years or greater in a significant proportion of patients with relapsed Hodgkin's disease.

A new serologic staging system for large-cell lymphomas based on initial beta 2-microglobulin and lactate dehydrogenase levels.

We report results of our investigation of prognostic factors for patients with large-cell lymphoma who were entered on the same treatment protocol and who had known pretreatment serum beta 2-microglobulin (beta 2M) and lactate dehydrogenase (LDH) levels. beta 2M and LDH levels were the most significant and independent variables for predicting time to treatment failure (TTF) and survival. The serum level of beta 2M correlated with tumor burden. These two serum markers defined three significantly different prognostic groups. All 27 patients in the low-risk group remain alive and in remission; in contrast, 22 of the 27 patients (81%) in the high-risk group have failed treatment, and only seven (26%) remain alive. In comparison with the Ann Arbor staging system, serum levels of beta 2M and LDH may provide a more precise system for defining risk groups and thereby allow a more rational approach to the development and analysis of treatment strategies.

Stage III follicular lymphoma: durable remissions with a combined chemotherapy-radiotherapy regimen.

From 1975 to 1982, 74 patients with stage III follicular lymphoma were treated with a combined modality protocol which included chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo), and radiotherapy to involved regions. This program resulted in a complete remission (CR) rate of 81%, a 5-year survival of 75%, and 5-year relapse-free survival (RFS) of 52% for all patients. Analysis of potential factors affecting treatment outcome revealed a significantly better CR rate for patients with small cleaved cell type (97%) than for patients with mixed (73%) or large-cell (57%) histologies. The 5-year survival was significantly better for patients with small cleaved (91%) and mixed (84%) cell types than for large cell (40%). In addition, bulky abdominal disease and elevated serum lactate dehydrogenase (LDH) were significant adverse prognostic factors for CR and for survival. Toxicity was moderate. No secondary leukemias have occurred. This combined modality regimen resulted in prolonged remission and potential cure for over half of patients who achieved CR, and is particularly encouraging for those with follicular small cleaved and mixed histologies.

Phase II trial of fludarabine phosphate in lymphoma: an effective new agent in low-grade lymphoma.

PURPOSE: In a phase II trial we investigated fludarabine phosphate (FAMP) as therapy for patients with relapsed lymphoma to determine its effectiveness and toxicity in this disease. PATIENTS AND METHODS: The 67 assessable patients had a median age of 56 years and had received a median of three chemotherapy regimens before treatment with FAMP. The starting dose was 25 mg/m2 administered intravenously over 30 minutes daily for 5 days every 3 to 4 weeks. RESULTS: High response rates were observed for follicular small cleaved-cell lymphoma (FSCCL) (62%), follicular mixed small- and large-cell lymphoma (80%), and follicular large-cell lymphoma (FLCL) (100%). Responses also occurred in small lymphocytic lymphoma (SLL) (33%), transformed lymphoma (33%), mycosis fungoides (40%), and Hodgkin's disease (25%). No responses were observed in other intermediate- or high-grade lymphomas (N = 20). Overall, there were five patients with a complete response, 23 patients with a partial response, and an overall response rate of 37%. Toxicity was primarily hematologic and infectious. No significant gastrointestinal, hepatic, renal, or neurologic toxicity occurred. CONCLUSIONS: We conclude that FAMP has major activity in follicular lymphoma. Fundamental research is needed to understand this differential efficacy in low-grade lymphoma yet lack of efficacy in intermediate- and high-grade lymphoma. Clinical investigations should be done using FAMP in varying dose schedules and in combination regimens.

Randomized study of growth factors post-peripheral-blood stem-cell transplant: neutrophil recovery is improved with modest clinical benefit.

PURPOSE: To evaluate the clinical value of growth factors (GFs) with peripheral-blood stem cells (PBSC) collected following mobilization with GFs, we randomized patients to receive or not to receive GFs following transplant. PATIENTS AND METHODS: Thirty-seven patients were apheresed after receiving the combination of granulocyte colony-stimulating factor (G-CSF) with granulocyte-macrophage colony-stimulating factor (GM-CSF) at doses of 10 micrograms/kg/d and 5 micrograms/kg/d, respectively, for 6 days before apheresis and during a median of 4 days of collections. One day after the infusion of autologous marrow and PBSC, patients were randomly assigned to receive no GFs or a combination of G-CSF (7.5 micrograms/kg/d) and GM-CSF (2.5 micrograms/kg/d), both as a 2-hour intravenous (i.v.) infusion twice per day until the neutrophil count was greater than 1,500/microL. RESULTS: The median days to recovery to an absolute neutrophil count (ANC) of 100/microL (9 v 11.5, P = .0005), 500/microL (10 v 16, P = .0004), or 1,000/microL (12 v 21, P = .0008) was shortened with the use of GFs, post-PBSC infusion. In addition, the duration of hospitalization was shorter (19 v 21 days, P = .0112) in the arm receiving GFs post-PBSC infusion. There was no significant difference between the two study arms in the duration of fever, documented septic episodes, or RBC or platelet transfusion requirements. CONCLUSION: Despite faster neutrophil recovery and shortened duration of hospitalization with GFs administered after PBSC transplantation, the measured clinical variables of febrile days, septic episodes, and transfusion requirements were similar between the study arms. The use of GFs post-PBSC transfusion is associated with a modest clinical benefit.

ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study.

PURPOSE: This study attempted to determine the efficacy of the combination of etoposide (VP-16), methyl-prednisolone, and cytarabine (Ara-C) with or without cisplatin in relapsing and refractory adult lymphoma patients. PATIENTS AND METHODS: The first 63 patients were randomized to receive VP-16 40 mg/m2/d for 4 days, methylprednisolone 500 mg intravenously daily for 5 days, and Ara-C 2 g/m2 intravenously over 2 to 3 hours on day 5 with or without cisplatin 25 mg/m2 IV administered by 24-hour infusion for 4 days (ESHA +/- P). Markedly different responses between ESHA (33%) and ESHAP (75%) led to deletion of the ESHA arm. A total of 122 patients on the ESHAP regimen were studied. RESULTS: Forty-five patients (37%) attained a complete remission (CR) and 33 (27%) attained a partial remission (PR), for a total response rate of 64%. The median duration of CR was 20 months, with 28% of remitters still in CR at 3 years. The overall median survival duration was 14 months; the survival rate at 3 years was 31%. Overall time to treatment failure (TTF) showed 10% of all patients to be alive and disease-free at 40 months. Response and survival rates were similar in patients with low-grade (n = 34), intermediate-grade (n = 67), transformed (n = 18), and high-grade (n = 3) lymphoma. The most significant factors for response and survival by multivariate analysis were the serum lactic dehydrogenase (LDH) level, tumor burden, and age (when analyzed as a continuous variable), while prior CR was highly significant by univariate analysis. A significant difference in survival was noted for patients with normal LDH levels and low- or intermediate-tumor burden or patients with low tumor burden and elevated LDH levels (55% 3-year survival rate) versus patients with elevated LDH levels and intermediate or high tumor burden (< 20%). Major toxicities included myelosuppression, with a median granulocyte count of 500/microL and platelet count of 70,000/microL. CONCLUSION: ESHAP was found to be an active, tolerable chemotherapy regimen for relapsing and refractory lymphoma. Applying a prognostic model based on tumor burden and serum LDH level shows significant differences in survival in this patient population.

Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP.

PURPOSE: We report the results of a prospective trial in which patients with relapsing non-Hodgkin's lymphomas were sequentially treated with two regimens (mesna, ifosfamide, mitoxantrone, and etoposide [MINE], and etoposide, methylprednisolone, cytarabine, and cisplatin [ESHAP]) if they had no history of disease resistance to these drugs. PATIENTS AND METHODS: Ninety-two patients received MINE (mesna 4 g/m2, ifosfamide 4 g/m2, mitoxantrone 8 mg/m2, and etoposide 195 mg/m2) for a maximum of six courses followed by ESHAP (etoposide 240 mg/m2, methylprednisone 500 mg/d, high-dose cytarabine 2 g/m2, and cisplatin 100 mg/m2) for three courses to consolidate complete response (CR) or for a maximum of six cycles after a partial response (PR) or no response to MINE. Pretreatment serum levels of lactate dehydrogenase (LDH) and beta 2-microglobulin (beta 2M) were documented in 80 of 92 patients. RESULTS: The response rate to MINE-ESHAP was 69% (48% CRs and 21% PRs), with a median survival time of 24 months and median time to treatment failure of 12 months. The median time to treatment failure according to histology was as follows: low-grade histologies, 16 months; low-grade transformed to intermediate-grade, 8 months; and intermediate-grade, 5 months. The most serious complication was myelosuppression, which resulted in two deaths due to neutropenic sepsis. A risk factor model based on beta 2M and LDH levels before salvage treatment showed three categories of risk, with 36-month survival rates as follows: low (beta 2M < 3 mg/dL and LDH normal), 61%; intermediate (beta 2M > or = 3 mg/dL or LDH above normal), 23%; and high (beta 2M > or = 3 mg/dL and LDH above normal), 0%. CONCLUSION: MINE-ESHAP is an effective salvage strategy for patients with recurrent lymphoma. Toxicity was acceptable. Factors that determine prognostic categories at relapse merit further study.

Clinical features and results of management of superior vena cava syndrome secondary to lymphoma.

Thirty-six of 915 patients with non-Hodgkin's lymphoma presented with superior vena cava syndrome (SVCS). The histologic types associated with SVCS were diffuse large cell in 23 patients, lymphoblastic in 12, and follicular large cell in one patient. Radiotherapy alone appeared equal to chemotherapy alone or in combination with radiotherapy in achieving relief of SVCS symptoms. Chemotherapy alone or in combination with radiotherapy was superior to radiotherapy alone in prolonging relapse-free survival and overall survival. No differences in relapse-free survival and survival were found between the patients treated with chemotherapy alone and those treated with chemotherapy and radiotherapy, but the addition of radiotherapy appeared to prevent local relapses in the group with large-cell lymphoma. The presence of symptoms of involvement of other mediastinal structures such as dysphagia, hoarseness, or stridor (DHS), a higher grade of intensity, and a shorter duration of symptoms (less than or equal to 2 weeks) appeared to adversely influence relapse-free survival and survival. The following conclusions were made: (1) a histologic diagnosis before the onset of treatment is desirable and feasible in patients presenting with SVCS except in those with severe respiratory distress, (2) both chemotherapy and radiotherapy are equally effective in alleviating the symptoms of SVCS, and (3) combined modality treatment with chemotherapy and radiotherapy results in a lower frequency of local relapses compared to chemotherapy alone but survival was similar in both groups.