Autologous stem-cell transplantation for non-Hodgkin's lymphomas: the role of graft purging and radiotherapy posttransplantation--results of a retrospective analysis on 120 patients autografted in a single institution

PURPOSE: To analyze retrospectively survival and prognostic factors of patients with non-Hodgkin's lymphoma (NHL) autografted from 1979 to 1995 in a single institution. PATIENTS AND METHODS: A total of 120 patients, 64 with aggressive and 56 with low-grade NHL, were autografted. The carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) regimen was used in 104. The autograft was marrow in 101 patients. Marrow was purged in vitro by mafosfamide for 63 patients (adjusted dose [AD] in 32; unique dose [UD] in 31); 27 patients received a CD34+-selected graft. Following intensification, 45 patients received additional radiotherapy on previous sites of involvement. RESULTS: Outcome at 5 years for patients transplanted with low-grade NHL in first complete remission (CR1), in first partial remission (PR1), and in second complete remission (CR2) or beyond showed an event-free survival (EFS) of 75% +/- 12%, 46% +/- 18%, and 57% +/- 24%, a relapse incidence (RI) of 21% +/- 12%, 49% +/- 19%, and 43% +/- 25%, and a transplant-related mortality (TRM) of 5% +/- 5%, 10% +/- 7%, and 0%, respectively. For patients with aggressive NHL transplanted in CR1, in PR1, in CR2 or beyond, and in resistant relapse or in primary refractory disease, the EFS was of 73% +/- 9%, 58% +/- 19%, 29% +/- 16%, and 10% +/- 9%, the RI 22% +/- 9%, 14% +/- 9%, 77% +/- 18%, and 66% +/- 20%, and the TRM 6% +/- 6%, 32% +/- 21%, 11% +/- 10%, and 71% +/- 22%, respectively. In patients autografted upfront in first remission, additional radiotherapy was associated with a higher EFS, in univariate (P = .03) and multivariate analysis (P = .02, relative risk [RR] = .021). The role of graft purging with mafosfamide on the outcome reflected by the dose of colony-forming unit-granulocyte-macrophage (CFU-GM) per kilogram infused postpurging was assessed by univariate analysis: patients in first remission who received lower doses of CFU-GM had a lower RI and a higher EFS. CONCLUSION: This retrospective analysis suggests that marrow purging and posttransplant radiotherapy improve the outcome of patients with NHL autografted in first remission.     

Passive immune globulin therapy in the SIV/macaque model: early intervention can alter disease profile

In this study, we investigated the impact of recombinant interleukin-2 (rIL-2) after high dose chemotherapy and autologous bone marrow transplantation (ABMT) in 25 patients with refractory or relapsed Hodgkin's disease (HD) (11 patients) and non Hodgkin's lymphoma (NHL) (14 patients). 48% of patients had resistant disease, 84% achieved complete remission after ABMT. rIL-2 was started at a median of 54 days post-transplant and consisted of a first cycle of 5 days followed by 4 cycles of 2 days every other week. Patients received a mean of 160 x 10(6) IU/m2 rIL-2 and hematological toxicity was moderate and transient. None of the 5 evaluable patients with measurable disease responded to rIL-2. After a 5 year median follow-up, the probability of survival and DFS is 72% (HD: 73% and NHL: 70%, p = NS) and 45% (HD: 36% and NHL: 48%, p = NS) respectively. These somewhat encouraging results warrant further evaluation of rIL-2 after ABMT in controlled studies, especially in NHL patients stratified for previous chemosensitivity.     

Prognostic factors for survival of non-Hodgkin's lymphoma patients treated with high-dose chemotherapy and autologous bone marrow transplantation

Prognostic factors to identify patients with high-risk non-Hodgkin's lymphoma (NHL) have recently been developed. We retrospectively investigated the relation between prognostic factors and treatment outcome after autologous bone marrow transplantation (ABMT). From 1984 to 1994, 80 consecutive patients with NHL responding slowly to or relapsing after front-line therapy were treated with high-dose chemotherapy and ABMT. Prognostic factors at the time of diagnosis and of ABMT were related to clinical outcome after ABMT. The cumulative 5-year overall survival (OS) was 51%, progression-free survival (PFS) 41%, and relapse-free survival (RFS) 53%. Absence of B symptoms and intermediate-grade malignancy at first presentation of disease were independently related to prolonged OS (P = 0.02 and P < 0.01, respectively) and prolonged PFS (P = 0.005 and P = 0.01, respectively). At the time of ABMT, first PR or CR, normal LDH levels and tumour stage I + II were associated with prolonged OS (P = 0.0005, P = 0.03 and P = 0.004, respectively). A Coiffier index of 0 or 1, first PR or CR and no extranodal disease involvement were related to prolonged PFS (P = 0.0002, P = 0.005 and P = 0.07, respectively). Treatment-related deaths occurred in 10% of patients. Assessment of disease status, LDH level, tumour stage, extranodal disease involvement and Coiffier index at the time of ABMT is respectively efficient in predicting treatment outcome after ABMT.     

Thought control strategies in acute stress disorder

Relapse after transplant for malignant lymphomas remains the main cause of treatment failure. Most conditioning regimens contain total body irradiation (TBI). We investigated the toxicity and efficacy of an intensified chemotherapy conditioning regimen without TBI in patients with relapsed or high-risk malignant lymphoma who had received prior radiation therapy and were therefore not eligible for TBI. Twenty patients with a median age of 38 (18-56) and relapsed or high-risk malignant non-Hodgkin's lymphoma (NHL, n = 16) or Hodgkin's disease (HD, n = 4) underwent high-dose chemotherapy consisting of busulfan (16 mg/kg), cyclophosphamide (120 mg/kg) and etoposide 30 mg/kg (n = 8) or 45 mg/kg (n = 12) followed by peripheral stem cell support (n = 14), autologous bone marrow (n = 3), allogeneic (n = 2) or syngeneic (n = 1) transplantation. All but two had chemosensitive disease before high-dose chemotherapy. The main toxicity -- according to the Bearman score -- was mucositis II in 18 (90%) patients; five patients (25%) suffered a grade I hepatic toxicity. GI toxicity I occurred in three (15%) and renal toxicity I in two patients (10%). Sixty percent of the patients developed transient dermatitis with erythema and three of them (15%) had skin desquamation; one patient experienced asymptomatic pancreatitis. Toxicity was slightly higher in patients treated with 45 mg/kg etoposide. One patient (5%) died of treatment-related venoocclusive disease. After a median follow-up of 50 months (24-84) the disease-free and overall survival were 50% and 55%. One of the nine relapsing patients developed secondary AML 18 months after transplant. High-dose busulfan, cyclophosphamide and etoposide is an effective regimen resulting in long-term disease-free survival in 50% of patients with relapsed malignant lymphoma and prior radiation therapy. The toxicity is moderate with a low treatment-related mortality (5%).     

Autologous bone marrow transplantation in poor-prognosis intermediate-grade and high-grade B-cell non-Hodgkin's lymphoma in first remission: a pilot study

PURPOSE: Using high-dose therapy and autologous bone marrow transplantation (ABMT) to overcome cellular resistance and eradicate minimal disease, we initiated a pilot study during first remission in patients with non-Hodgkin's lymphoma (NHL) to examine whether the long-term disease-free survival (DFS) rate can be improved for patients with poor-prognosis intermediate/high-grade NHL. PATIENTS AND METHODS: Twenty-six patients with advanced-stage diffuse intermediate/high-grade B-cell NHL (including 16 patients with diffuse small cleaved-cell [DSC]) were selected at presentation by histologic and clinical characteristics to have less than a 25% probability of long-term DFS with conventional treatment. After induction chemotherapy, 16 patients were in complete remission (CR) and 10 were in a minimal disease state. Patients were then treated with high-dose cyclophosphamide, total-body irradiation (TBI), and anti-B-cell monoclonal antibody-purged ABMT. RESULTS: Following ABMT, no acute in-hospital treatment deaths occurred, and engraftment of granulocytes and platelets was significantly faster than for patients undergoing ABMT who were in second or subsequent remission. Of 26 patients, 21 remain in CR maintained without continued therapy, three relapsed in sites of prior nodal disease (4.8, 5.4, and 28 months post-ABMT), and two died in remission. The DFS rate is estimated to be 85% at 28 months and thereafter. The median follow-up period for the 21 patients who are alive and disease-free is 32 months. CONCLUSION: This pilot study suggests that consolidation of first remission with ABMT may improve the long-term DFS rate for diffuse intermediate/high-grade NHL patients at high risk for relapse.     

Autologous bone marrow transplantation for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia following MDS. Chronic and Acute Leukemia Working Parties of the European Group for Blood and Marrow Transplantation

Intensive chemotherapy followed by autologous bone marrow transplantation (ABMT) may provide an alternative therapy for young patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia following MDS (sAML) lacking a suitable donor. We report the results for 79 patients with MDS/sAML transplanted with autologous marrow in first complete remission (CR). Within the total group of 79, a cohort of 55 patients for whom the duration of first CR was known were compared with a matched control group of 110 patients with de novo AML. The 2-year survival, disease-free survival (DFS), and relapse rates for the 79 patients transplanted in first CR were 39%, 34%, and 64%, respectively. The relapse risk was greater than 55% for all stages and all disease categories. Patients younger than 40 years had a significantly (P = .04) better DFS (39%) than patients older than 40 years (25%). The DFS at 2 years was 28% for the cohort of 55 patients transplanted for MDS/sAML and 51% for those transplanted for de novo AML (P = .025). Relapse rates were 69% for patients with MDS/sAML and 40% for those with de novo AML (P = .007). ABMT for MDS or secondary leukemia results in a lower DFS when compared with similarly treated patients with de novo AML due to a higher relapse rate. The DFS of 28% for these patients suggests that autotransplantation may be a valuable therapy for this disease. The low treatment-related mortality rate of less than 10% supports the view that sufficient numbers of hematopoietic stem cells are present in patients with MDS to allow adequate repopulation after autologous stem-cell transplantation.     

Features of the lateralization of speech function in stutterers as a function of the sex of the subjects

BACKGROUND: To analyze the response to eradicative therapy and prognostic factors in 52 patients with primary gastrointestinal lymphoma (PGIL) diagnosed at a single institution in a 13 year period. PATIENTS AND METHODS: The main clinical, biological and evolutive data were recorded. Pathologic diagnosis of PGIL was made according to the Working Formulation. Clinical stage was determined by the Ann Arbor system modified by Mushoff. The results of therapy as well as the influence of such characteristics on complete remission (CR), disease-free survival (DFS) and overall survival (OS) were studied. RESULTS: Mean age of the series was 53 years (SD 15). Thirty patients were males. HIV infection preceded PGIL diagnosis in 10 cases. Seventeen had bad performance status (ECOG 2-4) and 30 B symptoms. The PGIL localization was gastric in 31 cases and 29 had a low grade malignant lymphoma. B phenotype was demonstrated in 98% and 22 patients presented advanced stages (IIE2-IV). Treatment was radical surgery followed by intensive chemotherapy in 32 cases, intensive chemotherapy alone in 17, and surgical resection in 3. CR was obtained in 34 patients and 6 of them relapsed. The projected DFS from CR at 9 years was 72% and OS was 26%. CR and survival were not influenced by PGIL localization and treatment type. The main unfavourable prognostic factors were advanced stage (CR and OS), B symptoms (DFS and OS) and advanced ECOG score (CR, DFS and OS). Previous HIV infection had an independent prognostic influence on both CR and OS. CONCLUSIONS: In patients with PGIL, the achievement of CR, DFS and survival have been independent of the type of eradicative treatment used. Performance status, B symptoms and clinical stage have been the main prognostic factors. HIV infection carried an independent prognostic significance.     

Autologous stem cell transplantation (ASCT) for poor prognostic Hodgkin's disease (HD): comparative results with two CBV regimens and importance of disease status at transplant

Clinical outcome of 47 consecutive patients with advanced HD who underwent ASCT in our Department was analyzed retrospectively. Median age was 28 years (28 males and 19 females). At transplant, 15 (32%) patients were in CR (five in first CR after two chemotherapy regimens and 10 in second CR), eight (17%) in PR (seven without a prior CR), 22 (51%) had relapsing disease (19 with sensitive relapse) and two had primary refractory disease. The CVB regimen with two different schedules was used: 22 (47%) patients received standard CBV (CY 6 g/m2, BCNU 300 mg/m2 and etoposide 600 mg/m2) and 25 (53%) received an increased CBV dose (CY 7.2 g/m2, BCNU 440 mg/m2 and etoposide 2 g/m2). Antitumor response for 28 evaluable patients was similar for both CBV regimens: 87 and 75% (P=0.39). At 7.2 years, actuarial overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) for the whole series were 51.7+/-8%, 34+/-9% and 28+/-8%, with a median follow-up for the surviving patients of 3 years (0.7-7.6). No differences in these survival functions according to the CBV regimen used were observed (P=0.57). A history of a prior CR (P=0.003), duration of first CR >1 year (P=0.04), absence of bulky nodal disease at transplant (P=0.054), absence of extranodal disease at transplant (P=0.01), and a CR status at transplant (P=0.0006) were associated with a better PFS on univariant analysis. On multivariate analysis, only CR status at transplant remained significant (P=0.05). When patients in second CR at transplant and those in first sensitive relapse were analyzed separately, no differences in clinical characteristics or in treatment received pretransplant were observed; however, PFS was significantly different (P=0.01). In conclusion, CR status at transplant is useful in identifying 'good risk' patients and is necessary to obtain the greatest benefit from ASCT independent of the CBV regimen used.     

Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma. Results of a prospective randomized study

BACKGROUND: In a prospective randomized manner, this study evaluated the effect of adjuvant chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone; CHOP) in patients with Stage I non-Hodgkin lymphoma (NHL) who have achieved a complete response (CR) after radiation therapy (RT). METHODS: Forty-four patients with clinical or pathologic Stage I intermediate-grade or low-grade NHL were randomized to receive regional RT alone (median dose, 40 Gy) or regional RT followed by six cycles of CHOP chemotherapy. There were no differences in clinical and pathologic characteristics between the two treatment groups. RESULTS: The median follow-up was 7 years (range, 2-10 years). The actuarial relapse-free survival (RFS) rate for the RT plus CHOP group at 7 years was 83% compared with 47% (P < 0.03) for the RT-alone group. The overall survival (OS) for the two groups was 88% and 66%, respectively (P = 0.2). In patients with intermediate-grade NHL, the 7-year actuarial RFS for RT and CHOP was 86% compared with 20% for RT alone (P = 0.004). The corresponding actuarial survival rates were 92% and 47%, respectively (P = 0.08). In patients with low-grade histologic findings, the addition of adjuvant CHOP did not improve RFS (P = 0.6) or OS. All relapses in this study were at sites remote from the initially involved areas, and in 5 of 11 patients (45%), there were recurrences 5 years or longer after initial treatment. CONCLUSIONS: This study showed that adjuvant CHOP chemotherapy significantly improves RFS in patients with Stage I intermediate-grade NHL who achieve a CR after regional-field RT. The chemotherapeutic regimen favorably affected their probability of survival.     

Familial Hodgkin's and non-Hodgkin's lymphoma: different patterns in first-degree relatives

In order to evaluate the importance of genetic susceptibility in Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) we retrospectively analysed 31 families with lymphoma in first-degree relatives containing a total of 65 affected persons. We observed 20 HD/HD, 8 NHL/HD and 8 NHL/NHL pairs with median ages of diagnosis of 27, 36 and 48 years, respectively (p < 0.001). In HD/HD sib pairs were predominant in contrast to parent/child pairs in NHL/NHL (p = 0.04). There was a higher frequency of diseases with impaired immune function in NHL/NHL than in other pairs (p = 0.01). Comparison of ages and times of incidence of the pairs as well as sex-concordance rates are consistent with an age-specific genetic susceptibility to HD, but suggest a time-specific exposure in some NHL-prone families with or without compromised immune function.     

A radioreceptor assay for mass measurement of inositol (1,4,5)-trisphosphate using saponin-permeabilized outdated human platelets

PURPOSE: To evaluate the therapeutic efficacy of moderate-dose total abdominopelvic irradiation (TAI) in a retrospective series of pretreated non-Hodgkin's lymphomas (NHL). METHODS AND MATERIALS: From 1977 to 1994, 45 patients received TAI after failure of chemotherapy (CT). According to the Working Formulation, 10 patients were diagnosed with class A (group I), 19 with class B, C, or D (follicular) (group II), and 16 with class E or more severe (group III) NHL. Irradiation consisted of two daily fractions of 0.80 Gy each for a total dose of 20 Gy. RESULTS: Mean follow-up after TAI was 102 months (range 8-156). For the entire group, the complete response (CR) rate was 66%, the partial response (PR) rate 29%, 10-year overall survival (OS) 35%, 10-year disease-free survival (DFS) 29%, and median survival 32 months. When results between subgroups were compared, CR was 70% in group I, 84% in group II, and 44% in group III; and survival was statistically higher in group II than in groups I and III: 10-year OS 52% vs. 10% (p < 0.01) and 31% (p < 0.05), respectively, 10-year DFS 37% vs. 10% (p < 0.03) and 19% (p < 0.05), respectively. Grade III or IV complications were gastrointestinal in 27% of patients and hematologic in 25%. CONCLUSION: Large-field irradiation in moderate doses could provide an alternative to bone marrow transplantation in refractory NHL, especially in cases showing a follicular growth pattern.     

Nodular lymphocyte predominance Hodgkin's disease: long-term observation reveals a continuous pattern of recurrence

We evaluated the presenting clinical characteristics and outcome of 68 patients with nodular lymphocyte predominance Hodgkin's disease (NLP-HD), in order to delineate the pattern of evolution of the disease. The male to female ratio was 46/22 and median age 35 yrs (range, 14-86). Eight patients had a history of benign hyperplasia on lymph node biopsies performed 6 to 36 months before the diagnosis of NLP-HD. Early stage disease accounted for 75% of cases. One patient had a coexistent non-Hodgkin's lymphoma (NHL). Treatment was as follows: radiotherapy in 26, chemotherapy in 23, combined modality in 19. CR rate was 93% (63/68). 18 patients relapsed as HD and 5 developed NHL. The cumulative risk of NHL was 9% at 10 yrs. During remission, 4 patients had 5 episodes of follicular hyperplasia histologically documented. Overall survival rate was 71% at 10 yrs and and 63% at 15 yrs. Freedom from progression (FFP) declined from 67% at 5 yrs to 45% at 10 yrs, because of late relapses. Localized disease predicted for a better FFP (p = 0.01), but was not associated with a reduced risk of recurrence over time. NLP-HD is characterized by an indolent course with a constant pattern of relapse over time, also in patients with early stage disease at diagnosis. In addition to relapse as NLP-HD, patients may evolve into a NHL or develop benign lymph nodal hyperplasia. Careful long-term follow up is needed for these patients.     

Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA)

Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T-cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.     

Indications and relative indications for stem cell transplantation in non-Hodgkin's lymphoma

High dose chemotherapy with or without total body irradiation and autologous stem cell rescue has proven to be effective treatment to cure patients with relapsed intermediate grade and high grade non-Hodgkin's lymphoma. Important factors for selection of candidates most likely to do well with these approaches include patients whose disease is responsive to conventional therapy and those who have minimal disease volume at the time of transplant. The treatment-related mortality of autologous stem cell transplantation has diminished from 20% to less than 5% with improved supportive care and selection of patients with less advanced disease. Although the treatment-related mortality of allogeneic stem cell transplantation may be as high as 20-40%, a graft versus lymphoma effect may decrease relapse with the result that overall survival is not substantially different between autologous and allogeneic transplantation. The definitive indications for stem cell transplantation include patients who have relapsed with intermediate or high grade NHL. Relative indications include intermediate/high grade non-Hodgkin's lymphoma patients, "high risk" first complete remission (CR), resistant relapse; low grade non-Hodgkin's lymphoma in sensitive or resistant relapse, advanced disease (sensitive or resistant relapse, transformation), first CR (younger patients). Relative contraindications include specific patient profiles such as bulky high grade lymphoma which progresses on appropriate conventional therapy, poor performance status, active serious infection, serious cardiac, renal, pulmonary or liver dysfunction, active, central nervous system (CNS) disease unresponsive to cranial irradiation/intrathecal therapy. For patients with previous marrow involvement or active marrow involvement at the time of harvest or transplant, "purged" autografts, peripheral blood stem cell transplantation and allografts have been used successfully.     

Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucémies Aigu?s Myéloblastiques (GOELAM)

Three intensive consolidation strategies are currently proposed to younger adults with acute myeloid leukemia (AML) in first complete remission (CR): allogeneic or autologous bone marrow transplantation (BMT) and intensive consolidation chemotherapy (ICC). Patients aged 15 to 50 years with de novo AML received an induction treatment with 7 days of cytarabine and either idarubicin or rubidazone. After achievement of a CR, patients up to the age of 40 and having an HLA-identical sibling were assigned to undergo an allogeneic BMT. All the other patients received a first course of ICC with high-dose cytarabine and the same anthracycline as for induction. They were then randomly assigned to either receive a second course of ICC with amsacrine and etoposide or a combination of busulfan and cyclosphosphamide followed by an unpurged autologous BMT. Of 517 eligible patients, 367 had a CR, but only 219 (59.5%) actually received the planned intensive postremission treatment (73 allogeneic BMT, 75 autologous BMT, and 71 ICC). With a median follow-up of 62 months, the 4-year disease-free survival (DFS) of the 367 patients in CR was 39.5%. The 4-year overall survival (OS) of the 517 eligible patients was 40.5%. In multivariate analysis, DFS and OS were influenced only by the initial white blood cell count and by the French-American-British classification. The type of postremission therapy had no significant impact on the outcome. There was no difference in the 4-year DFS and OS between 88 patients for whom an allogeneic BMT was scheduled (respectively, 44% and 53%) and 134 patients of the same age category and without an HLA-identical sibling (respectively, 38% and 53%). Similarly, there was no difference in the outcome between autologous BMT and ICC. The 4-year DFS was 44% for the 86 patients randomly assigned to autologous BMT and 40% for the 78 patients assigned to ICC (P = .41). The 4-year OS was similar in the two groups (50% v 54.5%, P = .72). The median duration of hospitalization and thrombocytopenia were longer after autologous BMT (39 v 32 days, P = .006, and 109.5 v 18.5 days, P = .0001, respectively). After a first course of ICC, a second course of chemotherapy is less myelotoxic than an unpurged autologous BMT but yields comparable DFS and OS rates.     

Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLCL) is characterized by a marked degree of morphologic and clinical heterogeneity. We studied 156 patients with de novo DLCL for rearrangements of the BCL2, BCL6, and MYC oncogenes by Southern blot analysis and BCL2 protein expression. We related these data to the primary site of presentation, disease stage, and other clinical risk factors. Structural alterations of BCL2, BCL6, and MYC were detected in 25 of 156, 36 of 116, and 10 of 151 patients, respectively. Three cases showed a combination of BCL2 and BCL6 rearrangements, and two cases had a combination of BCL6 and MYC rearrangements. BCL2 rearrangement was found more often in extensive (39%) and primary nodal (17%) lymphomas than in extranodal cases (4%) (P = .003). BCL2 rearrangement was present in none of 40 patients with stage I disease, but in 22% of patients with stage II to IV (P = .006). The presence of BCL2 rearrangements did not significantly affect overall survival (OS) or disease-free survival (DFS). In contrast, high BCL2 protein expression adversely affected both OS (P = .008) and DFS (P = .01). BCL2 protein expression was poorly correlated with BCL2 rearrangement: only 52% of BCL2-rearranged lymphomas and 37% of BCL2-unrearranged cases had high BCL2 protein expression. Rearrangement of BCL6 was found more often in patients with extranodal (36%) and extensive (39%) presentation versus primary nodal disease (28%). No significant correlation was found with disease stage, lymphadenopathy, or bone marrow involvement. DFS and OS were not influenced by BCL6 rearrangements. MYC rearrangements were found in 16% of primary extranodal lymphomas, versus 2% of primary nodal cases (P = .02). In particular, gastrointestinal (GI) lymphomas (5 of 18 cases, 28%) were affected by MYC rearrangements. The distinct biologic behavior of these extranodal lymphomas was reflected by a high complete remission (CR) rate: 7 of 10 patients with MYC rearrangement attained complete remission and 6 responders remained alive for more than 4 years, resulting in a trend for better DFS (P = .07). These data show the complex nature of molecular events in DLCL, which is a reflection of the morphologic and clinical heterogeneity of these lymphomas. However, thus far, these genetic rearrangements fail as prognostic markers.     

A case of chronic B cell lymphocytic leukemia with expression of CD8 antigen on leukemic cells

PURPOSE: To determine the toxicity and prognosis of patients with relapsed and refractory diffuse aggressive non-Hodgkin's lymphoma (NHL) who underwent an autologous bone marrow transplant (ABMT) using augmented preparative regimens, treated in a major cooperative group setting, and to examine prognostic factors for outcome. PATIENTS AND METHODS: Ninety-four patients with either chemosensitive (50 patients) or chemoresistant (44 patients) relapse, including 22 who failed induction chemotherapy, were treated with high-dose cyclophosphamide and etoposide with total-body irradiation (TBI) (67 patients) or an augmented carmustine (BCNU), cyclophosphamide, and etoposide (BCV) preparative regimen (27 patients) and an ABMT at 16 Southwest Oncology Group (SWOG) transplant centers. All relapsing patients were required to undergo a minimum of two courses of salvage therapy to determine chemosensitivity before transplant. Overall (OS) and progression-free survival (PFS) were determined and a Cox regression model was used to assess potential prognostic variables. RESULTS: Of the 94 eligible patients, there were 10 (10.6%) deaths before day 50 posttransplant because of infection (six deaths), hemorrhagic alveolitis (three deaths), or bleeding (one death). The median 3-year PFS and OS for the entire group was 33% and 44%. For those with chemosensitive disease the PFS and OS were 42% and 55%, whereas for those with chemoresistant disease the PFS and OS were 22% and 29%. The PFS and OS for those failing induction chemotherapy were 27% and 32%. The relapse rates within the first 3 years for the chemosensitive relapse, chemoresistant, and induction failure groups were 61%, 40%, and 59%, respectively. For both PFS and OS, only disease status at transplant was a significant factor in the multivariate Cox model. CONCLUSION: These results single institutional pilot trials exploring augmented preparative regimens. Patients undergoing transplantation for resistant disease, particularly those failing induction chemotherapy, appear to have an improved prognosis as compared with reports using standard preparative regimens. Therapies other than manipulation of standard preparative regimens appear to be required to decrease relapses following autotransplantation.     

Burkitt's lymphoma in adults with and without human immunodeficiency virus infection: a single-institution clinicopathologic study of 75 patients

BACKGROUND: Burkitt's lymphoma (BL) accounts for 1-2% of all cases of non-Hodgkin's lymphoma (NHL) in the general population and for 35-40% in the setting of human immunodeficiency virus (HIV) infection. The authors report a 9-year single-institution experience with 75 adult BL patients (46 with and 29 without HIV infection) and compare the clinical and pathologic features of the disease in the two groups of patients. METHODS: Between May 1987 and June 1995, 131 patients with HIV infection and systemic NHL were diagnosed and treated at the National Cancer Institute in Aviano, Italy. In 46 cases (35%), the diagnosis was BL. During the same period, 29 of 1004 HIV negative NHL patients (2.8%) were diagnosed with BL and treated at the same institution. RESULTS: No statistical differences were found in the general characteristics of the two groups at the time that BL was diagnosed. Complete response rate was significantly lower for patients with HIV infection than for those without HIV infection (40% vs. 65%, P = 0.03). The median overall survival was significantly shorter for patients with HIV infection (7 months vs. not yet reached, P = 0.0001). However, the disease free survival (DFS) at 4 years was identical for the two groups of patients (74% for HIV positive patients vs. 73% for HIV negative patients, P = 0.70). CONCLUSIONS: The data from this study show that patients with BL with and without HIV infection share similar clinicopathologic characteristics at presentation. Although the median overall survival is significantly shorter for patients with HIV infection, the DFS is identical for both groups.     

Clinical analysis of elderly patients with malignant lymphoma

An epidemiological study on 173 consecutive elderly malignant lymphoma patients age 65 years or over was performed and the clinical outcome of chemotherapy is reported. Of there, 131 patients (75.7%) had non-Hodgkin's lymphoma (NHL) and 21 patients had Hodgkin's disease (HD). As for clinical staging, 58.9% of patients were in stage 3 or 4. The initial sites were nodal in 61.8% of the patients the most common sites of involvement in superficial lymph nodes being cervical, inguinal and axillar. The most frequent site of extranodal involvement was the gastrointestinal tract. The cases were treated with CHOP/COPP, BACOP or COP-BLAM combination chemotherapy. The clinical efficacy of these modalities was similar, with complete remission rates being about 50%. However, the total response rate (CR+partial remission) by the COP-BLAM regimen were 88.1%. The median survival time of cases achieving CR, was longer than 47 months. The most frequent cause of death was infection, especially pneumonia and septicemia. Many elderly ML patients were found and diagnosed when the disease developed to an advanced stage. Therefore it is necessary to make efforts to find early ML patients by screening apparently healthy elderly people. Improvement of the complete remission rate should be obtained if vigorous and intensive chemotherapy is carried out with careful supportive therapy concerning the general condition and complications in patients.