Factors affecting the development of atrial fibrillation and atrial flutter (AF/AFL) following autologous hematopoietic SCT (auto-HSCT).

The use of autologous hematopoietic SCT (auto-HSCT) has expanded to include older patients. Increasing age is a well-appreciated risk factor for the development of atrial fibrillation and/or atrial flutter (AF/AFL) in the general population. As more elderly patients undergo auto-HSCT, the risk of developing AF/AFL post transplant may also increase. However, few data evaluating other risk factors for the development of AF/AFL following auto-HSCT exist. Therefore, we performed a retrospective study to determine the incidence of AF/AFL following auto-HSCT and to determine the risk factors associated with the development of AF/AFL. Patients who developed AF/AFL were compared with a group of patients who received auto-HSCT within the same time period (April 1999 to May 2005) and were within 5 years of age. Of the 516 patients who underwent auto-HSCT at the University of Nebraska Medical Center 44 (8.5%) developed AF/AFL at a median time of 4 days (range, days 1-9) following auto-HSCT. In multivariate analysis, risk factors for developing AF/AFL were older age, odds ratio and 95% CI of 1.14 (1.07-1.21), elevated serum creatinine level, 2.69 (1.00-7.22), history of previous arrhythmia, 9.33 (3.01-28.99), and history of previous mediastinal irradiation, 11.12 (1.33-92.96).

Patients with grade 3 follicular lymphoma have prolonged relapse-free survival following anthracycline-based chemotherapy: the Nebraska Lymphoma Study Group Experience.

BACKGROUND: The aim of the study was to determine the outcome and clinical features predictive of survival in patients with follicular lymphoma (FL) treated aggressively and to determine the rate of disease-specific mortality in patients with grade 3 FL (FL3). MATERIALS AND METHODS: Four hundred and twenty-one patients with FL who were treated with various anthracycline-based chemotherapy regimens were included in this retrospective study. RESULTS: Patients with FL3 and a diffuse component of >50% had the worst outcome, with a hazard ratio of dying of 2.2 (95% CI 1.4-3.4) compared with patients with FL1 or FL2, and a ratio of 1.6 (95% CI 1.02-2.5) compared with FL3 with a diffuse component of < or =50% by multivariate analysis (P = 0.0026). Patients with FL3a had an outcome similar to those with FL3b. In patients with FL3 and a diffuse component of < or =50%, the overall and event-free survival curves showed a plateau for patients younger than 60 years of age. However, there were no differences in the cumulative incidence of relapse/progression or lymphoma-specific/treatment-related mortality between the two age groups. CONCLUSIONS: Less than half of the patients with FL3 and a diffuse component of < or =50% treated with anthracycline-based combination chemotherapy will relapse and relapses are uncommon after 6 years. Older patients should be offered the same aggressive chemotherapy as younger patients.

Hematopoietic stem cell transplantation in mantle cell lymphoma.

BACKGROUND: Patients with mantle cell lymphoma (MCL) have in general, lower response rates and overall survival (OS) than those with other B-cell non-Hodgkin's lymphomas. The role of hematopoietic stem cell transplantation (HSCT) in MCL is unclear. Hence we decided to study the clinical course of patients who received autologous and allogeneic HSCT for MCL. METHODS: Ninety-seven patients, (80 patients-autologous; 17 patients-allogeneic) who received a HSCT for mantle cell lymphoma were included in the study. RESULTS: The complete response rates at day 100 between the two groups were similar (73% vs. 62%). Day-100 mortality was higher in the allogeneic HSCT group (19% vs. 0%) (P < 0.01). The estimated 5-year relapse rates, 5-year event-free survival (EFS) and 5-year OS among the allogeneic HSCT patients were 21%, 44% and 49%, respectively, similar to 56%, 39% and 47% in the autologous group. Ten patients received HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone + high-dose methotrexate and cytarabine) +/- rituximab prior to transplant. There have been no relapses or deaths amongst these patients at a median follow-up of 16 months. CONCLUSIONS: Patients treated with allogeneic HSCT had a lower relapse rate, but similar EFS and OS to autologous HSCT. Treatment of MCL with HyperCVAD +/- rituximab followed by HSCT seems promising.

Immunological and clinical effects of post-transplant G-CSF versus placebo in T-cell replete allogeneic blood transplant patients: results from a randomized double-blind study.

BACKGROUND: Immunological and clinical effects of post-transplant growth factor administration have not been well studied. This report describes the outcome and immune functions of a total of 50 HLA-matched related donor allogeneic blood stem-cell transplantation patients who received post-transplant G-CSF (10 microg/kg) or placebo. METHODS: Immune status, including number of lymphocyte subsets and their functions, and serum immunoglobulin levels and clinical status--including GvHD, rate of relapse, event-free survival, and overall survival--were determined in the patients enrolled in this study. RESULTS: Twenty-eight patients survived 1 year after transplant, and 15 patients had available results to compare immune function by randomization assignment. At 12 months post-transplant, immune parameters in G-CSF versus placebo groups showed no statistically significant differences in number of circulating lymphocyte subsets CD3, CD4, CD8, CD19 and CD56 in the two groups. There was no significant (NS) difference in immunoglobulin IgG, IgA and IgM levels, NK or LAK cell-mediated cytotoxicity levels, and mitogen-induced proliferation between post-transplant G-CSF and placebo group. In addition, the analyses of immune parameters at earlier time-points on Days 28, 100, 180, and 270 revealed that, except for LAK cytotoxicity at Day 100, there was no differences between the two groups. Fourteen of 26 patients are alive in the G-CSF arm and nine of 24 in the placebo arm. Median follow-up of surviving patients is 43 months. Four year overall and event-free survival in the G-CSF and the placebo group were 53% and 35% (NS), and 44% and 36% (NS) respectively. Bacterial or fungal infections were the cause of six of 12 deaths in the G-CSF arm (all bacterial) and of four of 15 deaths in the placebo arm (two deaths from Aspergillus) (P=0.26). Two patients relapsed in the G-CSF arm and three in the placebo arm. Four year cumulative incidences of relapse were 8% versus 13% in G-CSF versus placebo arms, respectively, (NS). Chronic GvHD developed in 14 of 19 100-day survivors after G-CSF (11 extensive stage), and in 17 of 20 (14 extensive stage) in the placebo arm. The 4-year cumulative incidence of chronic GvHD was 56% [95% confidence interval (CI) 24-88%] after G-CSF and 71% (95% CI 48-94%) after placebo; this difference was not statistically significant (log rank P=0.41). CONCLUSION: In summary, there were no significant immunological or alterations in clinical benefit of post-transplant G-CSF administration in T-replete allotransplant recipients.

The International Prognostic Factors Project score for advanced Hodgkin's disease is useful for predicting outcome of autologous hematopoietic stem cell transplantation.

BACKGROUND: The International Prognostic Factors Project on Advanced Hodgkin's Disease developed a seven-factor prognostic score consisting of serum albumin, hemoglobin, gender, stage, age, leukocytosis and lymphocytopenia for newly diagnosed Hodgkin's disease patients who receive chemotherapy. The purpose of this study was to determine whether this prognostic score would also be useful for Hodgkin's disease patients undergoing autologous hematopoietic stem cell transplantation. PATIENTS AND METHODS: We performed a retrospective review of 379 patients who had autologous transplants for Hodgkin's disease, at the University of Nebraska Medical Center between October 1984 and December 1999. Multivariate analysis was performed to determine whether the prognostic factors identified by the International Prognostic Factors Project adversely influenced event-free survival (EFS) or overall survival (OS). RESULTS: Low serum albumin, anemia, age and lymphocytopenia were associated with poorer EFS and OS. Gender, stage and leukocytosis were not associated with significantly poorer outcomes. Estimated 10-year EFS was 38%, 23% and 7% for patients with 0-1, 2-3 or > or =4 of the adverse prognostic characteristics identified by the International Prognostic Factors Project, respectively. CONCLUSIONS: The prognostic score for advanced disease is also useful for relapsed and refractory Hodgkin's disease patients undergoing high-dose therapy followed by autologous hematopoietic stem cell transplantation.

Progenitor and lymphoma cells in blood stem cell harvests: impact on survival following transplantation.

This study evaluated whether cytokine-induced blood stem cell mobilization also mobilized lymphoma cells and whether lymphoma cell mobilization affected outcome post autologous blood stem cell transplant. Blood stem cell collections from 26 non-Hodgkin's lymphoma (NHL) patients harvested during steady-state (non-mobilized) and from 35 NHL patients harvested after cytokine administration (mobilized) were studied. The harvests were cultured and molecularly evaluated for clonal markers of the primary lymphoma. All patients underwent high-dose chemotherapy and autologous transplantation. Graft products from mobilized patients were more likely to contain lymphoma than graft products from non-mobilized patients (37% vs 19%) but this difference was not significant (P = 0.16). In a multivariate analysis, lymphoma contamination was not associated with patient age, gender, tumor grade, prior radiotherapy, duration of prior chemotherapy, mononuclear cell count, or the number of aphereses performed to obtain the product. Heavily pre-treated patients were less likely to have lymphoma-contaminated harvests (P = 0.064). Lymphoma contamination was positively associated with the number of progenitor cells collected (P = 0.047). In multivariate analyses, the only significant independent predictor of lymphoma contamination was the number of mononuclear cells collected (P = 0.031). Lymphoma contamination of transplanted apheresis products had no apparent impact on event-free and overall survival.

Transplantation of highly purified CD34+Thy-1+ hematopoietic stem cells in patients with recurrent indolent non-Hodgkin's lymphoma.

PURPOSE: To evaluate the results of high-dose chemotherapy and transplantation of highly purified "mobilized" peripheral blood CD34+Thy-1+ hematopoietic stem cells (HSCs) in patients with recurrent indolent non-Hodgkin's lymphoma (NHL) or mantle cell lymphoma (MCL). PATIENTS AND METHODS: Twenty-six patients with recurrent indolent NHL or MCL were mobilized witheither granulocyte colony-stimulating factor (G-CSF) alone or cyclophosphamide plus G-CSF. Apheresis was performed, and the product was purified using the Isolex immunomagnetic positive CD34+ cell selection device initially and subsequent high-speed flow-cytometric cell sorting for the final purification of CD34+Thy-1+ HSCs. The patients received high-dose chemotherapy with BEAC (carmustine, etoposide, cytarabine, and cyclophosphamide) followed by transplantation with the purified HSCs in 2 dose cohorts (cohort 1: > or =5 x 10(5) viable and pure HSC/kg; cohort 2: > or =3 x 10(5) HSC/kg). RESULTS: We attempted to mobilize 26 patients with G-CSF alone. Six patients did not collect adequate cells with G-CSF alone; subsequent mobilization with cyclophosphamide plus G-CSF was attempted, but adequate CD34+Thy-1+ HSCs could not be collected on these 6 patients. Twenty patients underwent transplantation with the BEAC transplantation regimen followed by purified HSCs. Patients in cohort 1 engrafted at a median of day 12 to an absolute neutrophil count (ANC) >500/microL, a median of day 19 for platelet transfusion independence, and a median of day 20 for red blood cell transfusion independence. Patients in cohort 2 engrafted at a median of day 12 to an ANC >500/microL, a median of day 12 for platelet transfusion independence, and a median of day 12 for red blood cell transfusion independence. Fourteen of the 20 patients had significant infections reported at some point posttransplantation, including influenza, respiratory syncytial virus, pneumonitis, and Pneumocystis carinii pneumonia. With a median follow-up of 38 months, 8 of the 20 patients have had progressive lymphoma and 5 patients have died. The 3-year event-free survival is 55%, and overall survival is 78%. CONCLUSIONS: CD34+Thy-1+ HSCs can be collected successfully from most lymphoma patients mobilized with G-CSF alone. The engraftment and disease outcomes in the patients in this small pilot study using these cells do not appear to be different from the outcomes of similar patients cited in the literature. However, the short- and long-term risks of infection were a concern in this patient population.

Autologous hematopoietic stem cell transplantation for mantle cell lymphoma.

This study evaluated the outcomes of patients who underwent high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (autoHSCT) for mantle cell non-Hodgkin's lymphoma and the effect of clinical and treatment characteristics. The clinical outcome and prognostic factors in 40 patients who underwent HDC and autoHSCT for mantle cell lymphoma between June 1991 and August 1998 were analyzed. With a median follow-up of 24 months for the surviving patients (range, 4-68 months), the 2-year overall survival was 65% and the 2-year event-free survival (EFS) was 36%. In univariate analysis, characteristics predictive of a poor EFS were blastic morphology (P = .019) and the patient having received 3 or more prior chemotherapy regimens (P = .004). In a multivariate analysis, the only factor associated with a poor EFS was the number of prior chemotherapy regimens. Those patients who received 3 or more prior therapies had a 2-year EFS of 0%, and those who received <3 therapies had a 2-year EFS of 45% (P = .004). Patients with mantle cell lymphoma can obtain prolonged EFS with HDC and autoHSCT; however, this strategy for prolonged EFS appears to work optimally in patients who are less heavily pretreated. Whether this therapy will increase the overall survival or EFS in patients receiving transplants in first complete remission will need to be tested in prospective randomized clinical trials.

A randomized, double-blind trial of filgrastim (granulocyte colony-stimulating factor) versus placebo following allogeneic blood stem cell transplantation.

Blood stem cell transplantation (BSCT) results in rapid hematopoietic recovery in both the allogeneic and autologous transplant settings. Because of the large numbers of progenitor cells in mobilized blood, the administration of growth factors after transplantation may not provide further acceleration of hematopoietic recovery. A randomized, double-blind, placebo-controlled study was performed to determine the effects of filgrastim (granulocyte colony-stimulating factor; G-CSF) administration on hematopoietic recovery after allogeneic BSCT. Fifty-four patients with hematologic malignancies undergoing a related, HLA-matched allogeneic BSCT were randomly assigned to receive daily filgrastim at 10 microg/kg or placebo starting on the day of transplantation. A minimum of 3 x 10(6) CD34(+) cells/kg in the allograft was required for transplantation. All patients received a standard preparative regimen and a standard regimen for the prevention of graft-versus-host disease (GVHD). The median time to achieve an absolute neutrophil count greater than 0.5 x 10(9)/L was 11 days (range, 9-20 days) for patients who received filgrastim compared with 15 days (range, 10-22 days) for patients who received placebo (P =.0082). The median time to achieve a platelet count greater than 20 x 10(9)/L was 13 days (range, 8-35 days) for patients who received filgrastim compared with 15.5 days (range, 8-42 days) for patients who received placebo (P =.79). There were no significant differences for red blood cell transfusion independence, the incidence of acute GVHD, or 100-day mortality between the groups. The administration of filgrastim appears to be a safe and effective supportive-care measure following allogeneic BSCT.

Mantle cell lymphoma. A clinicopathologic study of 68 cases from the Nebraska Lymphoma Study Group.

Although mantle cell lymphoma (MCL) is considered a distinctive disease entity within non-Hodgkin's lymphoma (NHL), the cytology and growth pattern of MCL can be quite variable and the clinical significance of these features is unclear. Also, the role of anthracyclines in the management of MCL is unclear. Therefore, we examined our experience with MCL in an effort to clarify these important issues. We identified 68 patients with MCL who were evaluated clinically and treated by the Nebraska Lymphoma Study Group. Treatment consisted of combination chemotherapy containing an anthracycline in 76% of the patients. The cases were grouped by blastic or lymphocytic cytology, and the latter were divided by growth pattern into nodular (or mantle-zone) and diffuse types. The clinical and pathological variables were then evaluated for their prognostic value. The median overall survival (OS) and failure-free survival (FFS) for the entire group were 38 months and 12 months, respectively, and there was no survival advantage for those who received an anthracycline. The cases were grouped as follows: blastic type, 26%; nodular lymphocytic type, 44%; and diffuse lymphocytic type, 30%. Both the cytology and pattern of growth were predictive of OS and FFS. The median OS was as follows: blastic type, 55 months; nodular lymphocytic type, 50 months; and diffuse lymphocytic type, 16 months (P = 0.0038). The clinical features that predicted for a shorter survival included bone marrow involvement, advanced stage disease, B symptoms, a poor performance score, and the International Prognostic Index. We conclude that new therapeutic approaches, with the patients stratified by histologic type and clinical prognostic factors, are clearly needed for MCL.

Phase I/II trial of multiple dose 131Iodine-MAb LL2 (CD22) in patients with recurrent non-Hodgkin's lymphoma.

The purpose of this to evaluate in a phase I/II study the efficacy and toxicity of a multi-dose administration of 131I labeled CD22 monoclonal antibody (131I-MAb-LL2) in escalating dose cohorts administered to relapsed non-Hodgkin's lymphoma (NHL) patients. Twenty-one patients with relapsed NHL received one of four dose levels of 131-MAb-LL2 administered in a twice weekly pattern. Starting with dose level 2, the patients also received 20 mg of unlabeled LL2 prior to each radiolabeled dose administered. Previously stored autologous peripheral blood progenitors were reinfused in case of prolonged cytopenias. Patients could repeat the same treatment if they had stable disease or a response to the first therapy at 8 weeks, and had not received their peripheral blood progenitors with the first cycle. Combining all of the dose cohorts, there were 5 complete responses or complete responses (undetermined) and 2 partial responses for a total response rate of 7/21 (33%). There was no dose response effect with responses documented at all dose levels. Expected toxicities were hematopoietic, requiring stem cell re-infusion in 5 patients. Other toxicities included hypothyroidism in 3 patients, and human anti-mouse antibody formation (HAMA) in 4 patients. In conclusion, 131I-MAb-LL2, when administered in a multi-dose fashion with 20 mg unlabeled antibody pre-dosing, resulted in a response rate of 33% in heavily pre-treated NHL patients. Non-hematologic toxicities were mild and few in number. Further evaluation of this treatment is warranted and further dose escalation will be possible.

Allogeneic bone marrow transplantation for lymphoma.

Registry data show that use of allogeneic transplantation for non-Hodgkin's lymphoma, and to a lesser extent, Hodgkin's disease is increasing. Although no prospective randomized trials have been performed, most comparisons show a significantly lower relapse rate when allogeneic transplant results are compared to results of autologous hematopoietic stem cell transplantation. The lower relapse rate following allogeneic transplantation, as well as several other lines of evidence, support the existence of a graft-versus-lymphoma effect. Nevertheless, in most comparisons, the lower relapse rate following allogeneic transplantation is offset by higher transplant-related mortality. These results make it difficult to find situations where definite overall survival advantages associated with the use of allogeneic transplantation can be demonstrated. The use of low-intensity non-myeloablative regimens for allogeneic transplantation is attracting attention. It is hoped that this approach may harness a graft-versus-lymphoma effect with less morbidity and mortality than conventional allogeneic transplantation, but more data are required to assess the value of this treatment.

Immune dysfunction despite high levels of immunoregulatory cytokine gene expression in autologous peripheral blood stem cell transplanted non-Hodgkin's lymphoma patients.

OBJECTIVE: In the present studies, we examined the role of immunoregulatory cytokine gene expression in immune reconstitution following high-dose chemotherapy and peripheral stem cell transplantation. MATERIALS AND METHODS: We analyzed the steady-state mRNA cytokine levels and the immune phenotype and function in the peripheral blood mononuclear cells from intermediate-grade non-Hodgkin's lymphoma patients prior to and following high-dose chemotherapy and peripheral stem cell transplantation. RESULTS: Significantly higher mRNA levels of both type 1 and type 2 cytokines and monokines were observed in patients undergoing high-dose chemotherapy and peripheral stem cell transplantation as compared with normal healthy individuals. Pretransplant mRNA levels of interleukin-2, -4, -8, -10, interferon-gamma and tumor necrosis factor-alpha were significantly higher than in normal individuals. In addition, on days 30 and 100 following transplantation interleukin-10 levels were significantly increased compared with pretreatment levels. In contrast, the levels of interleukin-2 mRNA and interferon-gamma were decreased significantly on day 365 compared with pretransplant levels. CONCLUSIONS: The high levels of cytokine mRNA transcripts, both prior to and following peripheral stem cell transplantation, were not due to an increased cellular frequency; rather, they appear to be due to abnormal cellular activation. However, T-cell function is significantly depressed compared with normal donors, which is associated with significantly higher levels of cellular-dependent T cell inhibitory activity and, we suggest herein, high levels of interleukin-10, a type 2 cytokine.

Clinical significance of the t(14;18) and BCL2 overexpression in follicular large cell lymphoma.

Follicular large cell lymphoma (FLCL) is an aggressive disease that responds to anthracycline-containing chemotherapy much like diffuse large B-cell lymphoma (DLBCL). Since the t(14;18) and/or bcl2 protein expression are less common in FLCL than in its low-grade counterparts, we sought to determine whether these features were predictive of survival as in DLBCL. We studied 50 patients with FLCL who were treated with curative intent. The t(14;18) was found by cytogenetic analysis in 56% of the patients and bcl2 protein was expressed by the tumor cells in 73%, but neither was predictive of survival. However, abnormalities of chromosome 17p and the presence of trisomy 21 were adverse predictors of survival, as were a number of clinical features. We conclude that neither the absence of the t(14;18) nor the lack of bcl2 expression explain the good response of a subset of patients with FLCL to curative therapy.

Partial review of immunotherapeutic pharmacology in stem cell transplantation.

In two separate lymphoma populations, we examined immune reconstitution following high dose chemotherapy (HDT) and bone marrow transplantation (BMT). In the first study we followed immune reconstitution for one year after HDT and BMT. In the second study we examined the ability of the orally active immunomodulator, Bestatin to augment immune reconstitution following HDT and BMT. The studies on immune reconstitution following HDT and BMT were undertaken in a cohort of non-Hodgkin's lymphoma (NHL) patients (n = 35) and examined the peripheral blood (PB) leukocyte subsets and their in vitro functions. Our results demonstrate that monocyte and natural killer (NK) cell engraftment occurred more rapidly then did T cell reconstitution. We also observed a significant decrease in the CD4:CD8 ratio post-transplantation as compared to normal PB donors due to a decrease in CD4+ cells. In addition, following HDT and BMT, measures of T cell function (phytohemagglutinin [PHA] mitogenesis) and T helper cell activity (pokeweed mitogen [PWM] mitogenesis) were consistently depressed as compared to cells from normal PB. Further, we demonstrate a correlation between the loss of T cell function and the frequency of circulating monocytes, suggesting a cause-effect relationship. Despite the dysfunction in T cells following HDT and BMT, immune-modulating agents can still augment the immune function. One such drug is Bestatin (ubenimex), an inhibitor of aminopeptidase (AP) that binds to CD13 on macrophage/monocytes. To examine its immune modulatory activity after HDT and BMT, a dose finding (10, 30, 90 and 180 mg/day) phase Ib trial was conducted with 30 Hodgkin's disease (HD) and NHL patients who received no drug (control), or Bestatin daily for 60 days following BMT. In these studies, Bestatin administration was initiated when the absolute neutrophil count was greater than 250/mm3 on two consecutive days. These studies revealed that Bestatin significantly increased the PHA and PWM responses in a dose-dependent manner. Flow cytometric analysis revealed a significant increase in NK cells (CD56+), B cells (CD19+), as well as the CD4:CD8 cell ratio. The latter observation was associated largely with a depression in the percent of CD8+ T cells as opposed to an increase in CD4+ T cells. We conclude that despite the peripheral tolerance observed following HDT and BMT, Bestatin could significantly increase some, but not all, immune surrogates.

Outcome of allogeneic stem cell transplantation for B cell chronic lymphocytic leukemia.

The objective of this study was to describe the outcome of allogeneic stem cell transplantation (alloSCT) in a series of patients with B cell chronic lymphocytic leukemia (B-CLL). Twenty-three B-CLL patients were transplanted between 1988 and 1997 using stem cells from a related (n = 20) or an unrelated donor (n = 3). The median age of the patients was 46 years, and the median number of prior chemotherapy regimens received was two. At transplantation, 14 patients had chemorefractory disease and 12 of these were refractory to fludarabine. The preparative regimens included total body irradiation (TBI) in 22 of the 23 cases. All patients received graft-versus-host disease (GVHD) prophylaxis with cyclosporine and methotrexate. Twenty patients (87%) achieved a complete remission (CR). The incidence of grade II-IV acute GVHD was 54%. Fourteen (61%) patients are alive and disease-free, including two with unrelated donors, at a median of 26 months (range, 9-115 months). Nine patients (39%) have died, one of whom had progressive B-CLL. The only favorable prognostic factor for failure-free survival (FFS) and overall survival (OS) after alloSCT was the use of a cyclophosphamide/TBI rather than an etoposide/cyclophosphamide/TBI regimen (P = 0.03). The projected 5-year FFS, OS, and relapse rates after alloSCT were 65% (95% CI, 48-88%), 62% (95% CI, 43-88%), and 5% (95%, CI 0-13%), respectively. These findings demonstrate the potential of high-dose therapy and alloSCT for inducing and maintaining a remission in patients with advanced or chemorefractory B-CLL. The low relapse rate may be due to an allogeneic graft-versus-leukemia effect.

Limited stage I and II follicular non-Hodgkin's lymphoma: the Nebraska Lymphoma Study Group experience.

The purpose of this study was to evaluate the outcome and prognostic factors of patients with limited stage follicular non-Hodgkin's lymphoma treated prospectively by the Nebraska Lymphoma Study Group (NLSG). Forty previously untreated patients, median age 64 years, with limited stage follicular lymphoma were prospectively treated according to the protocols of the NLSG between January 1980 and December 1990. The follicular large cell type represents 75% of the cases, and 14 of the biopsies also had a diffuse component (composite lymphoma). The initial treatment was radiation therapy (RT) to the involved field in 15 patients, anthracycline-containing combination chemotherapy (CT) in 20, and combined RT and CT in 5. Thirty-seven patients (92.5%) achieved a complete remission (CR). The median follow-up is 120 months (range, 20 to 214). Of the 37 patients achieving a CR, 7 patients are alive in first CR, one died due to sepsis, another because of a myeloproliferative disorder at 77 months following chemotherapy, 6 died because of unrelated causes in first CR. Twenty-two patients relapsed between 1 to 128 months following a CR. The estimated 10-year event-free survival is 21% (95% CI: 7 to 35). Two patients received no or palliative therapy after relapse and both died of progressive disease. Nineteen patients received salvage therapy and 15 achieved a second remission. The median survival after first relapse is 55 months. The estimated 10-year overall survival is 44% (95% CI: 28 to 60). Various factors including sex, histologic subtype, stage, and degree of follicularity do not influence the overall survival or event-free survival. CT with or without RT resulted in a better trend for 10-year event-free survival in stage IA patients compared to RT alone but estimated 10-year overall survival is no different. The overall survival is worse in the > or = 60 age group but this difference is not evident if data is adjusted for cause specific death. In conclusion, limited stage follicular lymphoma has an excellent initial response to radiation therapy or chemotherapy; however the recurrence rate is high and cure is limited.

Primary mediastinal large B-cell lymphoma: a clinicopathologic study of 43 patients from the Nebraska Lymphoma Study Group.

PURPOSE: To investigate whether primary mediastinal large B-cell lymphoma (PMLBL) is a distinct clinicopathologic entity with a more aggressive course than other diffuse large B-cell lymphomas (DLBL). MATERIALS AND METHODS: All patients with CD20-positive DLBL who presented with a mediastinal mass measuring at least 5.0 cm and were treated with curative intent were identified. A control group of 352 patients with nonmediastinal DLBL was selected for comparison. RESULTS: The 43 patients with PMLBL had a male to female ratio of 20:23 and a median age of 42 years. Stage I/II disease was present in 58% of the patients, with only 9% having bone marrow involvement. A complete remission was achieved in 63% of the patients, and the 5-year overall and failure-free survivals were 46% and 38%, respectively. Among the clinical variables, an elevated serum lactate dehydrogenase level, a low performance score, more than one extranodal site, and an intermediate or high International Prognostic Index score were predictive of poor survival. When compared with the DLBL group, a younger median age was the only clinical feature that was significantly different in the PMLBL group. CONCLUSION: The clinical features of PMLBL do not appear to be significantly different from those of nonmediastinal DLBL. Although the younger age of onset, slight female predominance, mediastinal location, and size of the mass may justify the recognition of PMLBL as a clinical syndrome, additional evidence is needed to define it as a distinct disease entity.