ALBERT

Description: It is debated whether follicular large cell lymphoma (FLCL) has a clinical behavior that is distinct from indolent follicular lymphomas, and whether there is a subset of patients who can be potentially cured. We report here our experience with 100 FLCL patients treated at our institution since 1984 with three successive programs. We evaluated the predictive value of pretreatment clinical features, including two risk models, the Tumor Score System and the International Prognostic Index (IPI). With a median follow-up of 67 months, the 5-year survival is 72% and the failure-free survival (FFS) is 67%, with a possible plateau in the FFS curve, particularly for patients with stage I-III disease. Features associated with shorter survival included age ≥60, elevated lactic dehydrogenase (LDH) or beta-2-microglobulin (β2M), advanced stage, and bone marrow involvement. Stage III patients had significantly better survival than stage IV patients (P 

Description: It is debated whether follicular large cell lymphoma (FLCL) has a clinical behavior that is distinct from indolent follicular lymphomas, and whether there is a subset of patients who can be potentially cured. We report here our experience with 100 FLCL patients treated at our institution since 1984 with three successive programs. We evaluated the predictive value of pretreatment clinical features, including two risk models, the Tumor Score System and the International Prognostic Index (IPI). With a median follow-up of 67 months, the 5-year survival is 72% and the failure-free survival (FFS) is 67%, with a possible plateau in the FFS curve, particularly for patients with stage I-III disease. Features associated with shorter survival included age ≥60, elevated lactic dehydrogenase (LDH) or beta-2-microglobulin (β2M), advanced stage, and bone marrow involvement. Stage III patients had significantly better survival than stage IV patients (P 

Description: Optimal therapy for patients (pt) with B-cell RIL remains controversial, and many treatment options include rituximab (R). Based on phase I–II studies of FND (fludarabine 25 mg/m2, d1–3; mitoxantrone 10 mg/m2, d1; dexamethasone 20 mg d1–5) treatment for RIL in which we observed a 48% CR rate, we studied the combination of R (375 mg/m2 d1) and FND for pt with RIL. Pt could not have received prior fludarabine, and were eligible if they had not previoiusly received R or had a response lasting at least 6 months (mo) to prior treament with R. Cycles were repeated every 4 weeks, and required an absolute neutrophil count of 1,000 and a platelet count of 100,000 to administer each cycle. Forty-two pt were entered onto this trial; however, one never received therapy after signing consent, and two were deemed ineligible after signing consent because of low cardiac ejection fractions (EF). All pt underwent biopsy prior to therapy; histologies included follicular gr1–3 in 30 pt, small lymphocytic in 7, marginal zone in 2. The median age was 58 (range 39–84) and median prior therapies 1 (range 1–3). The median number of cycles of R-FND delivered per patient was 6 (range 1–8). Of the 39 eligible and evaluable pt, 19 entered CR and 9 CRu for a CR/CRu rate of 72%, and 9 entered PR (23%) for an overall response rate of 95%. One had stable disease (SD), and one progression (PD). Eight underwent high dose therapy followed by autologous stem cell transplant (SCT) following a response to R-FND therapy. Five of these had achieved CR/CRu with R-FND after 1–6 cycles, and 3 PR after 2–6 cycles. In all, 14 of the 37 responders to R-FND (37%) have had progression; however, none of the 8 who underwent SCT has had progression, nor has the one with SD. In, 24 (62%) still remain free of progression with a median follow-up for living pt of 32 mo. In all, 6 pt have died of PD, including 4 who were ineligible for or refused SCT. The 2-year failure-free survival (FFS) and overall survival (OS) results for all pt are 66% and 90%. The 2-year FFS for responders is 66%, and the 2-year OS for all pt, with pt undergoing SCT censored at time of SCT is 81%. As expected, the main toxicity following R-FND was hematologic: gr 4 neutropenia occurred in 15 pt and in 15 of 130 cycles for which information is available, and gr 3–4 thrombocytopenia in 5 pt and in 6 cycles. In all, 13 of the 28 responders received less than 6 cycles of therapy; reasons included prolonged thrombocytopenia in 4, early SCT in 6, asymptomatic decrease in EF in one, and physician’s choice in 2. No patients died of acute toxicity while receiving R-FND. We conclude that 1) R-FND is a very active and well tolerated regimen for relapsed indolent lymphomas 2) Results appear very favorable compared to prior studies with FND 3) In this population, patients receiving R-FND were able to undergo SCT, and had very favorable outcomes.

Description: Patients with Hodgkin’s disease, which is either refractory or recurs after frontline chemotherapy with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone), ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or both regimens, generally have a poor prognosis. High-dose chemotherapy with autologous marrow or stem cell rescue (ABMT) is now a widely used salvage strategy in these patients. In this study, our objective was to determine the response rate to ASHAP (Adriamycin = doxorubicin, Solumedrol = methylprednisolone, High-dose Ara-C = cytosine arabinoside, and Platinum = cisplatinum), in a group of patients with Hodgkin’s disease with such poor risk characteristics. The treatment was intended as a brief tumor reducing program before ABMT. Fifty-six patients with diagnosed relapsed or primary refractory Hodgkin’s disease underwent this treatment. The program consisted of the administration of two cycles of ASHAP chemotherapy (doxorubicin 10 mg/m2/d intravenous (IV) continuous infusion (CI) over 24 hours, days 1 to 4; methylprednisolone 500 mg/d IV over 15 minutes daily for 5 days; cisplatinum 25 mg/m2/d IV CI over 24 hours, days 1 to 4; cytosine arabinoside 1.5 g/m2/d IV over 2 hours on day 5). After two courses of ASHAP the patients were evaluated for response, including a gallium scan test. Patients with progressive disease were taken off the study. Those with responding or stable disease received a third course of ASHAP, followed by consolidative treatment with ABMT. There were 19 complete responses (34% CR), 20 partial responses (36% PR), and 17 treatment failures, including 8 with minor responses and 9 with disease progression. Thus, in total there were 39 responses out of 56 patients (CR + PR = 70%). Myelosuppression was the main toxicity. There were no deaths due to toxicity. At this time, 23 patients are alive. There were 31 deaths due to disease progression and 2 due to other causes. The initial response to ASHAP before subsequent ABMT consolidation treatment correlated with survival. All 17 patients in whom ASHAP failed to achieve a response have died. The presence of B symptoms at relapse, and a duration of response to the last regimen of ≤6 months, predicted a poor response to ASHAP. A short program of treatment with ASHAP is an effective tumor debulking approach in patients previously treated with both or either ABVD and MOPP, before ABMT.

Description: Patients with Hodgkin’s disease, which is either refractory or recurs after frontline chemotherapy with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone), ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or both regimens, generally have a poor prognosis. High-dose chemotherapy with autologous marrow or stem cell rescue (ABMT) is now a widely used salvage strategy in these patients. In this study, our objective was to determine the response rate to ASHAP (Adriamycin = doxorubicin, Solumedrol = methylprednisolone, High-dose Ara-C = cytosine arabinoside, and Platinum = cisplatinum), in a group of patients with Hodgkin’s disease with such poor risk characteristics. The treatment was intended as a brief tumor reducing program before ABMT. Fifty-six patients with diagnosed relapsed or primary refractory Hodgkin’s disease underwent this treatment. The program consisted of the administration of two cycles of ASHAP chemotherapy (doxorubicin 10 mg/m2/d intravenous (IV) continuous infusion (CI) over 24 hours, days 1 to 4; methylprednisolone 500 mg/d IV over 15 minutes daily for 5 days; cisplatinum 25 mg/m2/d IV CI over 24 hours, days 1 to 4; cytosine arabinoside 1.5 g/m2/d IV over 2 hours on day 5). After two courses of ASHAP the patients were evaluated for response, including a gallium scan test. Patients with progressive disease were taken off the study. Those with responding or stable disease received a third course of ASHAP, followed by consolidative treatment with ABMT. There were 19 complete responses (34% CR), 20 partial responses (36% PR), and 17 treatment failures, including 8 with minor responses and 9 with disease progression. Thus, in total there were 39 responses out of 56 patients (CR + PR = 70%). Myelosuppression was the main toxicity. There were no deaths due to toxicity. At this time, 23 patients are alive. There were 31 deaths due to disease progression and 2 due to other causes. The initial response to ASHAP before subsequent ABMT consolidation treatment correlated with survival. All 17 patients in whom ASHAP failed to achieve a response have died. The presence of B symptoms at relapse, and a duration of response to the last regimen of ≤6 months, predicted a poor response to ASHAP. A short program of treatment with ASHAP is an effective tumor debulking approach in patients previously treated with both or either ABVD and MOPP, before ABMT.