Salvage therapy with ProMACE-MOPP followed by intensive chemoradiotherapy and autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma who failed to respond to first-line CHOP.

PURPOSE: We used alternative chemotherapy immediately followed in early-response patients by high-dose chemoradiotherapy and autologous bone marrow transplantation (ABMT) to treat patients with non-Hodgkin's lymphoma (NHL) who had failed to respond to first-line chemotherapy. PATIENTS AND METHODS: Thirty-one patients with NHL of intermediate- or high-grade malignancy who had failed to respond to first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy were treated. Seventeen patients had primary refractory disease and 14 had relapsed from first complete response (CR). The treatment consisted of prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, mechlorethamine, vincristine, and procarbazine (ProMACE-MOPP) salvage chemotherapy, followed, in case of responsive disease (at least partial response [PR]), by high-dose cyclophosphamide and total-body irradiation (TBI) with ABMT. RESULTS: Twenty-eight of 31 (90%) patients achieved PR (23 patients) or CR (five patients) with ProMACE-MOPP, and three failed to respond. Seventeen of 28 (61%) patients who responded underwent the ABMT procedure, which resulted in CR in 14 patients (82%); three failed to respond. Eleven responsive patients were not transplanted because of residual bone marrow infiltration (five patients), patient refusal (four patients), and ProMACE-MOPP-related mortality (two patients). To date, nine patients are alive and in CR, seven with a median follow-up of 41 months (range, 17 to 84 months). Referring to the original CHOP treatment, five of 17 (29%) patients with primary refractory disease remain free of disease at a median of 36 months after ABMT, and four of 14 (29%) patients in first relapse remain free of disease at a median of 33 months after ABMT. One patient died of AMBT-related toxicity. CONCLUSION: ProMACE-MOPP salvage chemotherapy produces a high early-response rate in patients who fail to respond to first-line CHOP, and more than half of the responding patients can be scheduled to receive ABMT, resulting in disease-free survival (DFS) at 3 years in 50% of the transplanted patients and in 25% of the original number of patients intended to receive this treatment.

Prophylactic cranial irradiation in limited disease small-cell lung cancer in complete remission: a retrospective analysis.

Recently a meta-analysis showed an improved survival probability of prophylactic cranial irradiation (PCI) in limited disease small-cell lung cancer (LD SCLC) in complete remission after chemotherapy. We evaluated treatment results of PCI+ and PCI- in these patients. Whether PCI (n = 65) or no PCI (n = 37) was administered did not depend either on patients or on tumour characteristics. After 2 years the incidence of brain metastases was 11% in PCI+ patients and 51% in PCI- patients. Both disease-free survival and overall survival were significantly longer after PCI. PCI reduces the incidence of brain metastases, prolongs brain metastases-free period, and overall survival in LD SCLC patients in complete remission after chemotherapy.

Intensive cytoreductive therapy followed by autologous bone marrow transplantation for patients with hematologic malignancies or solid tumors.

Fifty patients were studied. Twenty patients with non-Hodgkin's lymphomas (NHL) of high-grade malignancy and 21 patients with acute leukemia (AL) were treated with high-dose cyclophosphamide and total body irradiation, and three patients with Hodgkin's disease (HD) and six patients with solid tumors were treated with high-dose cyclophosphamide and VP16-213. Those procedures were followed by autologous bone marrow transplantation (ABMT). All patients had received conventional chemo(radio)therapy before the ABMT procedure. Although remissions were obtained in patients with cytotoxic drug-resistant diseases (lymphomas and solid tumors), none has become a long-term survivor, as occurred also in patients with solid tumors in partial remission (PR). Two of five patients with NHL in PR at the time of ABMT have become long-term disease-free survivors (28+, 56+ months). Ten patients with NHL were treated in complete remission (CR) and seven are in unmaintained CR; four with long follow-up (14+ to 59+ months). All patients with AL were treated in CR; two patients received ABMT in second CR, and both relapsed. Ten of nineteen patients in first CR relapsed; eight are alive in CR, five with long follow-up. Four deaths were therapy-related, all were patients in poor clinical condition. Intensive cytoreductive therapy followed by ABMT can produce prolonged disease-free survival (and probably cure) in a fair number of patients with poor risk NHL in CR and PR and probably also in patients with acute myeloblastic leukemia in first CR. This procedure was not successful in achieving long-term disease-free survival in patients with refractory lymphomas or solid tumors.

Allogeneic bone marrow transplantation with a fixed low number of T cells in the marrow graft.

Despite prophylaxis with immunosuppressive drugs, severe acute graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in patients transplanted with unmodified bone marrow (BM) grafts from HLA-identical siblings. Although T-cell depletion of the BM graft has evolved as the most effective method to prevent severe acute GVHD, this beneficial effect is counterbalanced by an increased rate of graft failure and relapse of the disease. To find an approach to T-cell depletion that may avoid these extreme risks, we gave BM recipients a fixed low number of 1 x 10(5) donor T cells per kilogram of recipient's body weight in the graft. This corresponds with 99% T-cell depletion and is achieved by the addition of T cells to the graft that was previously depleted of T cells. A total of 70 patients with hematologic malignancies or aplastic anemia, including 40 patients with standard-risk leukemias, received BM grafts, depleted of T cells according to this approach, from HLA-identical siblings. The preparative regimen consisted of cyclophosphamide and total body irradiation. The patients also received a short course of cyclosporine posttransplant. Graft failure did not occur. Acute GVHD, only grade I or II, was seen in 70% of the patients and was limited to the skin in all patients. Chronic GVHD occurred in 31% of the patients and, with the exception of 1 patient, was limited to the skin as well. Relapse occurred in 3 of 40 (8%) patients with standard-risk leukemias, resulting in a projected survival at 5 years of 80%. Patients with standard-risk diseases had a procedure-related mortality of 11%. Quality of life, determined 1 year after BM transplant, was good in almost all patients with standard-risk diseases. Thus, this approach of T-cell depletion may be an approach that avoids the development of severe acute and chronic GVHD without damaging the function or antileukemic effect of the graft and that has a low transplant-related morbidity and mortality.

Intensive cytotoxic therapy followed by autologous bone marrow transplantation for non-Hodgkin's lymphoma of high-grade malignancy.

Fourteen patients with non-Hodgkin's lymphoma (NHL) of high-grade malignancy were treated with cyclophosphamide and total body irradiation followed by autologous bone marrow transplantation (ABMT). All patients were pretreated with conventional chemotherapy. Three of four patients with drug-resistant disease achieved complete remission (CR), but relapse occurred within six months. Four patients in partial remission (PR) achieved CR; one died because of sepsis, two relapsed within six months, and one is still in CR 28+ months later. Six were treated in CR, five in first CR, and one in second CR. From these six patients (who received this treatment as consolidation therapy), five are in unmaintained CR seven to 31+ months after ABMT (one patient died of a secondary illness). There were two therapy-related deaths, both in patients with a poor clinical condition. Toxicity of this treatment was mild for those receiving transplants who were in better condition. These preliminary results suggest that intensive cytoreductive therapy followed by ABMT may improve disease-free survival in patients in NHL of high-grade malignancy in CR.