High-dose chemotherapy and hematopoietic stem cell rescue in patients with relapsed Hodgkin's disease

Abstract

Fifty-one consecutive patients with Hodgkin's disease (HD) have been treated with high-dose chemotherapy (HDT) and transplantation of autologous bone marrow (BM) (n = 44), autologous BM plus peripheral blood stem cells (PBSC) (n = 2), PBSC (n = 1), syngeneic (n = 1), or allogeneic BM (n = 3). All patients had received standard salvage chemotherapy prior to HDT and were classified as sensitive (n = 33) or resistant (n = 17) to this treatment; one patient was in untreated relapse prior to BMT. The preparative regimens for patients receiving autologous BM and/or PBSC consisted of cyclophosphamide, VP 16, and BCNU (CVB) (n = 44) or BCNU, etoposide, ara-C, and melphalan (BEAM) (n = 3). The patients receiving allogeneic transplants were treated with the CVB regimen (n = 2) or busulfan (16 mg/kg body wt.) and cyclophosphamide (200 mg/kg body wt.). With a median follow-up of 12 months, overall survival for 44 patients grafted with autologous BM is 61% +/- 9%, progression-free survival for patients with sensitive disease is 44% +/- 11%; no patient with resistant relapse survived beyond 1 year post transplant. Two of three patients grafted with allogeneic BM still survive 15 and 24 months after BMT with Karnofsky performance scores of 70% and 100%, respectively. The main toxicity encountered with the CVB regimen was interstitial pneumonia (IP), seen in four of 15 patients (27%) receiving > or = 600 mg/m2 of BCNU. Three of these patients have died. The results show that HDT followed by hematopoietic stem cell rescue may effectively salvage an important fraction of patients with relapsed HD who respond to standard chemotherapy. The same approach is largely unsuccessful in patients with proven refractoriness to standard chemotherapy. Whether HDT followed by BMT or PBSC support is superior to intensive chemotherapy without stem cell support can be answered only by a prospectively randomized trial.

High-dose CEB vs BEAM with autologous stem cell transplant in lymphoma

“…Previous studies have included small numbers of patients but reported roughly 26-28% occurrence of post-transplant noninfective pulmonary complications with CEB. 1,[5][6] These studies used a BCNU dose of 600 mg/m 2 or higher. It is apparent from these studies that BCNU pulmonary toxicity is dose related, but it remains unclear why our study reports a low occurrence rate.…”

“…Doses greater than 600 mg/m 2 are not well tolerated with a higher risk of development of posttransplant noninfective pulmonary complications, marked mucositis, and increased cases of infection. [1][2][3][4][5][6] In terms of efficacy, whether CEB or BEAM produces better survival outcome is unclear. There is a wide range of percentages of patients achieving complete remission in both the CEB and BEAM.…”

Acute left ventricular failure following melphalan and fludarabine conditioning

“…Keywords: emlphalan; fludarabine; BMT; cardiotoxity The alkylating agent melphalan, either alone or in combination with other agents such as busulphan and total body irradiation, has been widely used in myeloablative conditioning regimens prior to stem cell transplantation for diseases such as multiple myeloma, 1 non-Hodgkin lymphoma 2 and Hodgkin's disease. 3 The clinical utility of melphalan has recently been extended by the development of nonmyeloablative transplant regimens intended to exploit the graft-versus-tumour effect of allogeneic T cell chimerism whilst reducing the toxicities associated with myeloablative conditioning. 4 Non-myeloablative regimens have seen melphalan used in novel combinations with agents such as the purine analogue, fludarabine.…”

“…3 The clinical utility of melphalan has recently been extended by the development of nonmyeloablative transplant regimens intended to exploit the graft-versus-tumour effect of allogeneic T cell chimerism whilst reducing the toxicities associated with myeloablative conditioning. 4 Non-myeloablative regimens have seen melphalan used in novel combinations with agents such as the purine analogue, fludarabine.…”

Effective mobilisation of peripheral blood progenitor cells with 'Dexa-BEAM' and G-CSF: timing of harvesting and composition of the leukapheresis product

“…Both autologous bone marrow (BM) and peripheral blood progenitor cells (PBPC) have successfully been employed for restoring haematopoiesis after myeloblative cytotoxic therapy (Philip et al, 1987;Kessinger et al, 1989;Brandwein et al, 1991;Hardingham et al, 1993;Schmitz et al, 1993). Besides the possibility of less contamination by tumour cells, the major advantage of autologous PBPC transplantation (PBP-CT) over autologous BM transplantation (ABMT) appears to be a more rapid reconstitution of marrow function To et al, 1992).…”