The role of body mass index in survival outcome for lymphoma patients: US intergroup experience.

BACKGROUND: The role of body mass index (BMI) in survival outcomes is controversial among lymphoma patients. We evaluated the association between BMI at study entry and failure-free survival (FFS) and overall survival (OS) in three phase III clinical trials, among patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Hodgkin's lymphoma (HL). PATIENTS AND METHODS: A total of 537, 730 and 282 patients with DLBCL, HL and FL were included in the analysis. Baseline patient and clinical characteristics, treatment received and clinical outcomes were compared across BMI categories. RESULTS: Among patients with DLBCL, HL and FL, the median age was 70, 33 and 56; 29%, 29% and 37% were obese and 38%, 27% and 37% were overweight, respectively. Age was significantly different among BMI groups in all three studies. Higher BMI groups tended to have more favorable prognosis factors at study entry among DLBCL and HL patients. BMI was not associated with clinical outcome with P-values of 0.89, 0.30 and 0.40 for FFS, and 0.64, 0.67 and 0.09 for OS, for patients with DLBCL, HL and FL, respectively. The association remains non-significant after adjusting for other clinical factors in the Cox model. A subset analysis of males with DLBCL treated on R-CHOP revealed no differences in FFS (P = 0.48) or OS (P = 0.58). CONCLUSION: BMI was not significantly associated with clinical outcomes among patients with DLBCL, HD or FL, in three prospective phase III clinical trials. The findings contradict some previous reports of similar investigations. Further work is required to understand the observed discrepancies.

Efficacy of abbreviated Stanford V chemotherapy and involved-field radiotherapy in early-stage Hodgkin lymphoma: mature results of the G4 trial.

INTRODUCTION: To assess the efficacy of an abbreviated Stanford V regimen in patients with early-stage Hodgkin lymphoma (HL). PATIENTS AND METHODS PATIENTS: with untreated nonbulky stage I-IIA supradiaphragmatic HL were eligible for the G4 study. Stanford V chemotherapy was administered for 8 weeks followed by radiation therapy (RT) 30 Gy to involved fields (IF). Freedom from progression (FFP), disease-specific survival (DSS) and overall survival (OS) were estimated. RESULTS: All 87 enrolled patients completed the abbreviated regimen. At a median follow-up of 10 years, FFP, DSS and OS are 94%, 99% and 94%, respectively. Therapy was well tolerated with no treatment-related deaths. CONCLUSIONS: Mature results of the abbreviated Stanford V regimen in nonbulky early-stage HL are excellent and comparable to the results from other contemporary therapies.

An individual patient-data comparison of combined modality therapy and ABVD alone for patients with limited-stage Hodgkin lymphoma.

BACKGROUND: Treatment options for patients with nonbulky stage IA-IIA Hodgkin lymphoma include combined modality therapy (CMT) using doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) plus involved-field radiation therapy (IFRT), and chemotherapy with ABVD alone. There are no mature randomized data comparing ABVD with CMT using modern radiation techniques. PATIENTS AND METHODS: Using German Hodgkin Study Group HD10/HD11 and NCIC Clinical Trials Group HD.6 databases, we identified 588 patients who met mutually inclusive eligibility criteria from the preferred arms of HD10 or 11 (n = 406) and HD.6 (n = 182). We evaluated time to progression (TTP), progression-free (PFS) and overall survival, including in three predefined exploratory subset analyses. RESULTS: With median follow-up of 91 (HD10/11) and 134 (HD.6) months, respective 8-year outcomes were for TTP, 93% versus 87% [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.24-0.78]; for PFS, 89% versus 86% (HR 0.71, 95% CI 0.42-1.18) and for overall survival, 95% versus 95% (HR 1.09, 95% CI 0.49-2.40). In the exploratory subset analysis including HD10 eligible patients who achieved complete response (CR) or unconfirmed complete response (CRu) after two cycles of ABVD, 8-year PFS was 87% (HD10) versus 95% (HD.6) (HR 2.8; 95% CI 0.64-12.5) and overall survival 96% versus 100%. In contrast, among those without CR/CRu after two cycles of ABVD, 8-year PFS was 88% versus 74% (HR 0.35; 95% CI 0.16-0.79) and overall survival 95% versus 91%, respectively (HR 0.42; 95% CI 0.12-1.44). CONCLUSIONS: In patients with nonbulky stage IA-IIA Hodgkin lymphoma, CMT provides better disease control than ABVD alone, especially among those not achieving complete response after two cycles of ABVD. Within the follow-up duration evaluated, overall survivals were similar. Longer follow-up is required to understand the implications of radiation and chemotherapy-related late effects. CLINICAL TRIALS: The trials included in this analysis were registered at ClinicalTrials.gov: HD10 - NCT00265018, HD11 - NCT00264953, HD.6 - NCT00002561.

Rnx deficiency results in congenital central hypoventilation.

The genes Tlx1 (Hox11), Enx (Hox11L2, Tlx-2) and Rnx (Hox11L2, Tlx-3) constitute a family of orphan homeobox genes. In situ hybridization has revealed considerable overlap in their expression within the nervous system, but Rnx is singularly expressed in the developing dorsal and ventral region of the medulla oblongata. Tlx1-deficient and Enx-deficient mice display phenotypes in tissues where the mutated gene is singularly expressed, resulting in asplenogenesis and hyperganglionic megacolon, respectively. To determine the developmental role of Rnx, we disrupted the locus in mouse embryonic stem (ES) cells. Rnx deficient mice developed to term, but all died within 24 hours after birth from a central respiratory failure. The electromyographic activity of intercostal muscles coupled with the C4 ventral root activity assessed in a medulla-spinal cord preparation revealed a high respiratory rate with short inspiratory duration and frequent apnea. Furthermore, a coordinate pattern existed between the abnormal activity of inspiratory neurons in the ventrolateral medulla and C4 motorneuron output, indicating a central respiratory defect in Rnx mice. Thus, Rnx is critical for the development of the ventral medullary respiratory centre and its deficiency results in a syndrome resembling congenital central hypoventilation.

Enx (Hox11L1)-deficient mice develop myenteric neuronal hyperplasia and megacolon.

The isolated homeobox gene Enx (Hox11L1) is expressed in enteric neurons innervating distal ileum, and proximal and distal colon. Enx-deficient mice develop megacolon with massive distension of the proximal colon. The number of myenteric ganglia, total neurons per ganglion, and NADPH diaphorase presumptive inhibitory neurons per ganglion are increased in the proximal and distal colon, but decreased in the distal ileum of all Enx-/- mice. Enx-/- mice provide a model for human neuronal intestinal dysplasia (NID), in which myenteric neuronal hyperplasia and megacolon are seen. These results suggest that Enx is required for the proper positional specification and differentiative cell fate of enteric neurons.

Patterns of disease progression and outcomes in a randomized trial testing ABVD alone for patients with limited-stage Hodgkin lymphoma.

BACKGROUND: In the National Cancer Institute of Canada Clinical Trials Group/Eastern Cooperative Oncology Group HD.6 trial, progression-free survival was better in patients randomized to therapy that included radiation, compared to doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) alone. We now evaluate patterns of progression and subsequent outcomes of patients with progression. PATIENTS AND METHODS: After a median of 4.2 years, 33 patients have progressed. Two radiation oncologists determined whether sites of progression were confined within radiation fields. Freedom from second progression (FF2P) and freedom from second progression or death (FF2P/D) were compared. RESULTS: Reviewers agreed for the extended (kappa = 0.87) and involved field (kappa = 1.0) analyses. Progression after ABVD alone was more frequently confined within both the extended (20/23 vs. 3/10; P = 0.002) and involved fields (16/23 vs. 2/10; P = 0.02). There was no difference in FF2P between groups [5-year estimate 99% (radiation) versus 96% (ABVD alone)] [hazard ratio (HR) = 3.14, 95% confidence interval (CI) 0.63-15.6; P = 0.14]; the 5-year estimates of FF2P/D were 94% in each group (HR = 1.04, 95% CI 0.41-2.63; P = 0.93). CONCLUSION: Treatment that includes radiation reduces the risk of progressive Hodgkin lymphoma in sites that receive this therapy, but we are unable to detect differences in FF2P or FF2P/D.

Phase I evaluation of a synthetic mutant of beta-interferon.

A synthetic mutant of beta-interferon, produced by recombinant DNA technology, was prepared with serine substituted for the naturally occurring cysteine at amino acid 17. This molecule, after purification to homogeneity, was evaluated in 23 patients with cancer for tolerated doses, safety, and pharmacokinetics. Each patient was begun on twice weekly administration, one dose i.m., then an identical dose i.v. Doses, escalated weekly, were tolerated by 9 of 12 patients at 100 X 10(6) units i.m., 11 of 14 patients at 100 X 10(6) units i.v., and 8 of 10 patients receiving i.v. doses of 200 X 10(6) units. Fever (greater than or equal to 38.9 degrees C), the commonest cause for ceasing dose escalation, occurred in 11 of 13 patients who developed limiting i.v. toxicity and 6 of 11 who developed limiting i.m. toxicity. Patients who did not have progressive cancer after completion of dose escalation received five consecutive daily doses at their maximum tolerated single dose by each route, i.m. and i.v. These two 5-day treatments were given without difficulty. All patients treated with 300 X 10(6) units or less, i.m. (n = 13) or i.v. (n = 10), were able to receive five daily doses without limiting toxicity. Peak serum titers occurred immediately after i.v. administration and declined in an exponential manner thereafter. Despite absence of measurable titers in serum after i.m. injection, fever and significant (P less than 0.05) depression of WBC and platelet counts, serum calcium, and serum cholesterol occurred (prestudy to maximum tolerated dose). An immunoglobulin antibody to beta-interferon, detected by enzyme-linked immunoabsorbent assay, developed in 17 of 23 patients. Neutralizing activity (titer 10(2] was found in only 1 of 23 patients. No immune-mediated sequelae (symptomatic or renal) were identified. Further Phase I and II trials with this molecule will determine whether it will prove to have a better therapeutic index or different spectrum of therapeutic activity from alpha-interferon or gamma-interferon.

Retroperitoneal fibrosis following treatment for Hodgkin's disease.

With improvement and refinement of therapy, the majority of Hodgkin's disease patients are alive and free of disease at 5 years. As these patients continue to be observed, a variety of late complications have been reported. We describe herein three patients who developed retroperitoneal fibrosis following definitive therapy for Hodgkin's disease. The incidence approaches that seen with methysergide.

Vinblastine, bleomycin, and methotrexate: an effective adjuvant in favorable Hodgkin's disease.

Sixty-seven patients with favorable pathologic stage (PS) I and IIA or B or IIIA Hodgkin's disease were randomized to receive subtotal or total lymphoid irradiation (STLI/TLI) alone or involved field irradiation (IF) plus six cycles of a novel adjuvant chemotherapy containing vinblastine, bleomycin, and methotrexate (VBM). With a follow-up from 6 to 72 months (median, 37 months), the actuarial freedom-from-progressive disease (FFP) at 5 years is 70% after STLI/TLI and 95% after IF plus VBM. One death has occurred in the irradiation-only treatment group. The data for IF plus VBM are significantly superior to previous actuarial results at 5 years using IF alone (FFP = 35%, P less than .00001) and compare favorably with prior results with IF plus nitrogen mustard, vincristine, procarbazine, +/- prednisone (MOP[P]) chemotherapy (FFP = 80% at 5 years, P = .10). VBM is well tolerated with greater than 90% of calculated doses delivered. As anticipated, VBM has had relatively little adverse effect on male or female fertility. Selected pulmonary functions are reduced early after IF plus VBM to a greater degree than with irradiation of the mediastinum alone, but the differences are modest. Based upon our current numbers and follow-up, we can be 90% confident that VBM as an adjuvant to irradiation in favorable Hodgkin's disease is as effective, or even superior, to MOP(P) chemotherapy. Because of its lesser toxicity, adjuvant VBM may have a broader role in the management of Hodgkin's disease.

Follicular and diffuse mixed small-cleaved and large-cell lymphoma--a clinicopathologic study.

The clinical records and initial biopsy materials from 76 patients with mixed small-cleaved and large-cell lymphoma containing both a follicular and diffuse architectural pattern were reviewed. The characteristics of this group, treated at Stanford University Medical Center (SUMC) between 1963 and 1983, are described. The 5-year actuarial survival and freedom from progression are 70% and 27.5%, respectively. Classification according to the degree of follicularity indicated that patients with focally follicular areas (ie, less than 25% of the histologic section) have a significantly worse freedom from progression and overall survival at 5 years compared with those patients with a predominantly follicular architecture (ie, greater than 50% follicular areas). Based on our analysis, we feel that the degree of follicularity is an important prognostic factor and that mixed lymphoma patients with only focally follicular areas behave more like an intermediate-grade lymphoma and should be treated aggressively.

Diagnosis of B cell lymphoma by analysis of immunoglobulin gene rearrangements in biopsy specimens obtained by fine needle aspiration.

Histologic diagnosis of lymphoma is far more difficult in the disaggregated cells obtained by percutaneous aspiration of lymph nodes than in tissue sections prepared from excisional biopsy specimens. However, the simplicity, economy, and safety of aspiration biopsy makes this an attractive diagnostic option in certain situations. In the present study, we demonstrate that lymph node aspirates provide material that is both suitable and sufficient for accurately detecting clonal proliferations of B cells by analysis of immunoglobulin gene rearrangements. The rearrangements detected in aspirated tissue serve as clonal markers that can be directly compared with the rearrangements found in histologically confirmed lymphoma removed by open biopsy. The application of gene rearrangements to aspirated material therefore offers a useful method of diagnosing lymphoma, particularly for the purposes of more thorough staging at initial presentation or the evaluation of tissues for possible relapse.

Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: results of a tree-structured survival analysis.

While diffuse large-cell lymphoma (DLCL) is considered to be highly curable with current therapy, treatment failures are observed even with intensive combination chemotherapy regimens. In order to study the prognostic significance of actual dose intensity of chemotherapy in DLCL, we retrospectively analyzed 115 previously untreated patients treated as Stanford between 1975 and 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP), methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, and dexamethasone ([M]BACOD), or methotrexate, Adriamycin, cyclosphosphamide, vincristine, prednisone, and bleomycin (MACOP-B). The actual relative dose intensity (RDI), the amount of drug actually administered to each patient during the first 12 weeks of therapy, was calculated as standardized to CHOP and analyzed in addition to clinical factors prognostic for survival by univariate analysis. Multivariate recursive partitioning (tree-structured) survival analysis identified the actual RDI of Adriamycin greater than 75% as the single most important predictor of survival. A model incorporating the actual RDI of Adriamycin and performance status, in combination with serum lactate dehydrogenase (LDH) and extranodal disease, defined three overall prognostic groups of patients with respective 3-year survival rates of 89%, 63%, and 18%. The three prognostic groups remained distinct, even when restricted to complete responders. This model was also predictive of survival when dose intensity was analyzed relative to the optimum dose defined for each of the three regimens and when applied to a subgroup of patients aged 50 years or younger. We conclude that actual RDI is an important prognostic factor for survival in DLCL and that analysis of RDI early in the course of treatment may allow modification of the treatment plan.

Long-term survival after histologic transformation of low-grade follicular lymphoma.

PURPOSE: To describe the course of patients following histologic transformation (HT) from low-grade follicular lymphoma to intermediate- or high-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were identified from data bases in the Division of Oncology and the Department of Surgical Pathology. HT was defined as the conversion of a follicular small cleaved-cell or follicular mixed small cleaved-cell and large-cell lymphoma to a diffuse large-cell, diffuse mixed small cleaved-cell and large-cell or any high-grade lymphoma. RESULTS: We analyzed the clinical course of 74 low-grade lymphoma patients with histologically proven transformation occurring from 1965 to 1988. The median time from diagnosis to HT was 66 months, and the median age at HT was 58 years. The median duration of survival after transformation was 22 months. Anatomic extent of disease at HT (limited v extensive, P = .01), prior chemotherapy (none v any, P = .01), and response to therapy (complete v partial or none, P = .005) at time of HT were identified as significant predictors of survival after HT in backward-selection Cox regression analysis. Thirty patients attained a complete response to therapy at HT. They had a median survival duration of 81 months after HT. CONCLUSION: A subset of patients with HT from low-grade follicular lymphoma to intermediate- or high-grade lymphoma enjoys relatively long-term survival. Patients with limited disease and no previous exposure to chemotherapy have the most favorable prognosis.

Lymphomas presenting as histologically unclassified neoplasms: characteristics and response to treatment.

Malignant lymphoma is frequently diagnosed when immunohistochemical techniques are applied to otherwise unclassified neoplasms. In this analysis of 35 patients with a histologically unclassified neoplasm that expressed leukocyte-common antigen(s) (LCA), actuarial survival was 63%, and 45% of patients were free from disease progression at 30 months following treatment as for lymphoma. The clinical features at diagnosis and the results of combination chemotherapy were found to be similar to a group of patients with a diagnosis of diffuse large-cell lymphoma (DLCL) concurrently treated at this institution. This study further emphasizes the importance of improved diagnostic techniques in the management of histologically unclassified tumors.

Small lymphocytic lymphoma.

The clinical course of 54 patients with small lymphocytic lymphoma (SL) was reviewed. The majority of patients had disseminated lymphoma at the time of diagnosis; 14 patients (26%) presented with Ann Arbor stage I and II disease. Five- and 10-year survival for all patients was 76% and 49%. The only clinicopathologic features identified that predicted a shortened survival were the presence or absence of systemic (B) symptoms (15% v 63% at 10 years, P = .01) and a diffuse rather than pseudofollicular nodal architecture (47% v 87% at 10 years, P = .04). Initial bone marrow involvement was not an adverse prognostic factor for patients who presented with stage III and IV disease. Ten patients developed a marked lymphocytosis consistent with progression to a leukemic phase (chronic lymphocytic leukemia [CLL]). These ten patients had a median initial lymphocyte count of 2,790, compared with 1,580 for those patients who did not progress to CLL (P = .0001). Developing CLL did not adversely affect survival (P = .48). Thirty-seven patients were treated with various combinations of radiation and chemotherapy; 17 patients received no initial therapy. Ten-year freedom from relapse (FFR) for stage I and II patients treated with irradiation was 80% and 62%; FFR for stage III and IV treated patients was 11%. Despite the marked differences in FFR, no statistically significant difference in survival could be demonstrated between the various stages. Selected patients with advanced SL received no initial therapy; these patients had a 10-year survival that was not statistically different from the immediately treated stage III and IV patients. Patients with stage I and II SL should be treated with irradiation; prolonged FFR and possibly cure of the disease can be achieved in these patients.

Follicular large-cell lymphoma: intermediate or low grade?

PURPOSE: To evaluate the benefit of anthracycline-based chemotherapy, identify prognostic factors, and determine the value of the International Prognostic Factors Index for patients with follicular large-cell (FLC) lymphoma. PATIENTS AND METHODS: This retrospective study includes 96 patients with FLC lymphoma treated at Stanford University Medical Center between 1969 and 1991. Fifty-five patients received doxorubicin plus cyclophosphamide-containing chemotherapy regimens, 21 patients received other chemotherapy regimens, 15 patients received radiotherapy only, and five patients received no initial therapy. Thirty-four patients had stage I or II disease and 62 patients had stage III or IV disease. RESULTS: With a median follow-up duration of 5.2 years (range, 1 to 18), the actuarial 5- and 10-year overall survival rates were 75% and 54%, with actuarial 5- and 10-year freedom from progression (FFP) rates of 53% and 42%, respectively. Patients treated with chemotherapy regimens that contained both doxorubicin and cyclophosphamide had a superior actuarial 10-year FFP rate (55% v 25%, P = .06) and overall survival rate (65% v 42%, P = .04) compared with patients treated with other chemotherapy regimens. Only one patient treated with doxorubicin plus cyclophosphamide relapsed after 3 years. In the multivariate analysis, discordant lymphoma and treatment with chemotherapy regimens not containing both cyclophosphamide and doxorubicin predicted for worse FFP and overall survival rates. In addition, poor performance status and increasing areas of diffuse histology predicted for a worse survival, while anemia and male sex predicted for a worse FFP. The age-specific International Index was useful in predicting outcome; however, few patients with FLC lymphoma had high-risk features. CONCLUSION: The plateau in FFP implies that patients with FLC lymphoma enjoy sustained remissions after standard anthracycline-based chemotherapy. FLC lymphoma should continue to be approached as an intermediate-grade lymphoma with curative intent.

Effect of treatment for Hodgkin's disease on pulmonary function: results of a prospective study.

PURPOSE: Because each of very different treatments for Hodgkin's disease (HD) may result in a high rate of cure, attention is currently focused on toxicity. This prospective study was designed to assess the effects of mediastinal irradiation and bleomycin chemotherapy on pulmonary function. PATIENTS AND METHODS: Patients were treated from 1980 to 1990 on randomized controlled trials at Stanford University. Pulmonary function was tested before treatment (baseline), early after treatment (< 15 months), and more than 36 months posttherapy. Treatment options in the 145 patients were grouped as I (mediastinal radiotherapy), II (mediastinal radiotherapy plus bleomycin), and III (bleomycin) for analyses of variance (ANOVAs). A variety of regression models were used to predict early and late effects on pulmonary function. RESULTS: A decrease in forced vital capacity (FVC) and diffusing capacity (DLCO) in the first 15 months after treatment followed by recovery after 36 months was observed for most patients. Patients who received mediastinal radiotherapy (RT) had a more pronounced reduction in pulmonary function and less complete recovery. Overall, 3 or more years after treatment, 32% of group I patients, 37% of group II patients, and 19% of group III patients had FVC values less than 80% of predicted, while only 7% of patients had a DLCO less than 80% of predicted. Linear regression identified baseline measurement as the only significant predictor of change in percent predicted FVC or DLCO; patients with higher baseline values had greater decrements after therapy. Mantle RT was the only significant treatment variable, predictive of FVC and DLCO within 15 months and FVC at 36 or more months. No patient experienced pulmonary toxicity severe enough to require hospitalization. CONCLUSION: This prospective analysis of pulmonary function after treatment for HD showed that mediastinal RT was the only treatment variable that achieved statistical significance. Although there were no significant interactions between mediastinal RT and bleomycin or Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) chemotherapy, the patient numbers were small after correction for mediastinal mass size and drug regimen such that an effect could have been missed. The mild reduction in pulmonary function should be factored into the overall assessment of morbidity risk for each of the potentially curative treatments included in this study. As with all reports of late effects, these data should be interpreted with respect to the population tested, details of the treatment administered, methods of measurement, and length of follow-up.

Brief chemotherapy, Stanford V, and adjuvant radiotherapy for bulky or advanced-stage Hodgkin's disease: a preliminary report.

PURPOSE: Although survival rates have improved for patients with bulky and advanced-stage Hodgkin's disease (HD), current treatments entail substantial acute morbidity and risks for late effects such as infertility, second malignancies, and cardiopulmonary toxicities. A novel, brief chemotherapy regimen (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone [Stanford V]) was designed to shorten the duration of treatment, significantly reduce cumulative doses of alkylating agents, doxorubicin, and bleomycin, and maintain dose-intensity (DI). This brief chemotherapy was combined with radiation therapy (RT) to bulky disease sites. METHODS: Since May 1989, 65 previously untreated patients were treated for stage II HD with bulky mediastinal involvement (n = 21) or for stage III or IV HD (n = 44). Patients received weekly chemotherapy for 12 weeks. Consolidative RT was given to the first 25 patients to sites of initial bulky disease or radiographic abnormalities that persisted after chemotherapy; in the remaining 40 patients, RT was limited to bulky disease (adenopathy > or = 5 cm and/or macroscopic splenic nodules defined by computed tomography [CT]). RESULTS: With a median follow-up period of 2 years, actuarial 3-year survival rate is 96% and failure-free survival (FFS) rate is 87%. The 3-year FFS rate is 100% for stage II patients with bulky mediastinal disease and 82% for patients with stage III to IV disease. There were no treatment-related deaths. In a preliminary analysis on a subset of patients, female and male fertility appears to be preserved. CONCLUSION: These preliminary results indicate that the Stanford V chemotherapy regimen with or without RT is well-tolerated and effective therapy for bulky, limited-stage, and advanced-stage HD. Less cumulative exposure to alkylating agents, doxorubicin, and bleomycin and limited use of radiation is expected to decrease risks for second neoplasms and late cardiopulmonary toxicity. Based on these results, the Stanford V chemotherapy with or without RT regimen deserves further study in the context of a randomized clinical trial.

Similar outcome of treatment of B-cell and T-cell diffuse large-cell lymphomas: the Stanford experience.

Although previous studies have suggested a relatively poor prognosis for some patients with peripheral T-cell lymphoma, the clinical significance of immunologic phenotype in diffuse large-cell lymphoma (DLCL) remains controversial. One hundred one patients with a uniform morphologic diagnosis of DLCL treated at Stanford between 1975 and 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP), methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, and dexamethasone ([M]BACOD), or methotrexate, Adriamycin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy were studied with regard to immunologic phenotype. Immunologic analysis, performed on frozen or paraffin-embedded tissue, identified 77 cases of B-cell origin, 21 cases of T-cell origin, and three cases that lacked B-cell or T-cell markers. Analysis of complete remission (CR) rates (84% v 95%), 5-year actuarial freedom from disease progression (38% v 53%), and 5-year actuarial overall survival (52% v 79%) showed no statistically significant differences in prognosis between B- and T-cell patients, respectively. The 5-year actuarial survival of patients with stage IV T-cell DLCL (56%) also did not differ in a statistically significant way from stage IV B-cell patients (36%). We conclude that treatment selection for DLCL should not be based on immunologic phenotype alone.

Fractionated total-body irradiation, etoposide, and cyclophosphamide plus autografting in Hodgkin's disease and non-Hodgkin's lymphoma.

PURPOSE: High-dose etoposide was incorporated into a regimen of fractionated total-body irradiation (FTBI) and high-dose cyclophosphamide before autologous transplant with the goal to enhance the antitumor effect of the myeloablative regimen in poor-risk lymphoid malignancies. PATIENTS AND METHODS: Ninety-six patients, 24 with recurrent or refractory Hodgkin's disease and 72 with poor-risk non-Hodgkin's lymphoma (NHL), were treated on this study. Cytoreduction with conventional therapy was attempted before administration of the preparatory regimen. The preparatory regimen consisted of 12 Gy total-body irradiation administered in 10 1.2-Gy fractions on day -8 through day -5, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Patients with NHL received bone marrow purged with a panel of monoclonal antibodies and complement on day 0, while patients with Hodgkin's disease received peripheral-blood stem cells alone or with unmanipulated bone marrow. RESULTS: The major morbidities of transplant were mucositis and skin toxicity. Eight patients (8.6%) died of regimen-related toxicities within 100 days of transplant. Engraftment was related to the rescue product; the median time to a neutrophil count more than 500/microL was 10 days for patients with Hodgkin's disease and 16 days for NHL patients. With a maximum follow-up duration of longer than 5 years, the 3-year actuarial survival rate is 57%. At 3 years, the actuarial freedom from progression (FFP) rate is 55% and the event-free survival rate is 47% for patients with Hodgkin's disease, while the respective figures for NHL patients are 60% and 53%. Among 32 patients with intermediate- and high-grade lymphoma transplanted subsequent to first relapse, 70% are free of lymphoma and 60% are event-free at > or = 3 years. CONCLUSION: The preparatory regimen consisting of FTBI, etoposide, and cyclophosphamide demonstrates relative efficacy in patients with Hodgkin's disease and NHL selected for high-dose therapy. Longer follow-up duration is needed to determine the rate of cure and to assess late complications. Major remaining challenges for high-dose therapy are a more inclusive strategy for all poor-risk patients and the need to reduce posttransplant relapses.