The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease. A single-center eight- year study of 155 patients

Abstract

Although high-dose chemotherapy and autologous bone marrow transplantation (ABMT) are increasingly being used for the treatment of relapsed and resistant Hodgkin's disease, there have been few large, single-center studies reported with adequate follow-up to allow full evaluation of this therapeutic modality. We present 155 poor-risk Hodgkin's disease patients who received high-dose BEAM (BCNU, etoposide, cytosine arabinoside, and melphalan) chemotherapy and ABMT who have been studied over a period of 8 years. All patients had either not attained a remission on mechlorethamine, vincristine, procarbazine, prednisone-type therapy and had poor prognostic features at presentation, not attained a complete remission or relapsed within 1 year of an initial alternating regimen, or not attained remission with two or more lines of treatment. At the time of ABMT the relapse status of the patients was as follows: 46 patients were primarily refractory to induction therapy, 7 were good partial responders, 52 were in first relapse, 37 in second relapse, and 13 in third relapse. Seventy-eight patients had chemoresistant disease, 33 had chemosensitive disease at the time of ABMT, and 44 were untested for chemosensitivity at latest relapse. The procedure related mortality in the first 90 days post-ABMT of 10% overall. At 3 months 43 patients (28%) were assessed as complete responders, 72 patients had a partial response (46%), and 24 patients (16%) had no response or progression of disease. However, by 6 months, 53 (24%) patients were assessed as complete responders and 51 (33%) patients had nonprogressive disease. Forty-five patients had received radiotherapy post-ABMT to residual masses (41 patients) or to previous sites of bulk disease (4 patients). The actuarialoverall and progression-free survival at 5 years was 55% and 50%, respectively. On multivariate analysis patients with bulk (masses >10 cm), heavily pretreated patients (those receiving three or more lines of treatment) and females had a significantly poorer prognosis. Relapse status was also significant for progression-free survival in that patients in second (60%) and third relapse (70%) had a better prognosis than those in first relapse (44%) or with primary refractory disease (33%). Response to prior chemotherapy did not predict for progression-free survival. These results enable comparisons to be made between high-dose chemotherapy with ABMT and conventional dose salvage therapy. Furthermore, although the results as a whole are highly encouraging, certain groups carry an unfavorable prognosis.

Preliminary experience of allogeneic stem cell transplantation for lymphoproliferative disorders using BEAM–CAMPATH conditioning: an effective regimen with low procedure‐related toxicity

“…This paper describes our preliminary experience of the BEAM regimen for allogeneic transplantation in lymphoproliferative disorders. The BEAM regimen has been extensively used before autologous transplantation and it is well tolerated with low incidence of side-effects and a TRM of < 10% (Chopra et al, 1993). We reasoned that BEAM would be a suitable conditioning regimen for allogeneic transplantation.…”

“…This low toxicity contrasts with the results obtained using CVB as conditioning for allogeneic BMT in lymphoma (Demirer et al, 1995) in which there was a high TRM due primarily to pulmonary toxicity, which was seen particularly in those patients who received doses of BCNU of 600 mg/m 2 . The dose of BCNU conventionally used in BEAM is only 300 mg/m 2 , and a low incidence of pulmonary toxicity has been seen after autologous transplantation using this dosage (Chopra et al, 1993).…”

“…In conclusion, our preliminary experience suggests that the toxicity of BEAM±CAMPATH is similar to that seen after autologous transplantation. An additional advantage of this regimen is the fact that fertility, at least in some women, is maintained (Chopra et al, 1993). There has been a striking low incidence of acute and chronic GVHD and longer followup will be required to determine whether this is maintained and whether this has an impact upon relapse risk.…”

High risk of hepatitis B‐virus reactivation after hematopoietic cell transplantation in hepatitis B core antibody‐positive patients

“…All autologous transplant patients with multiple myeloma were conditioned with high-dose melphalan and those with malignant lymphoma were conditioned with either BEAM (carmustine, VP-16, cytosine-arabinoside, melphalan) (10) or MCVC (ranimustine, carboplatin, etoposide, cyclophosphamide) (11) depending the on physician's preference. One autologous HSCT patient with acute myelogenous leukemia (AML) was conditioned with high-dose busulfan (16 mg ⁄ kg), cytosine arabinoside (12 g ⁄ m 2 ) and etoposide (40 mg ⁄ kg).…”

Allogeneic transplantation for Hodgkin lymphoma

“…Interpretation of the literature regarding ASCT in primary refractory HL is complicated by the lack of application of a standard definition for this entity (Chopra et al, 1993;Bierman et al, 1994;Reece et al, 1995;Horning et al, 1997;Andre et al, 1999;Lazarus et al, 1999;Sweetenham et al, 1999;Josting et al, 2000;Sureda et al, 2001;Ferme et al, 2002;Czyz et al, 2004;Moskowitz et al, 2004;Lavoie et al, 2005;Morabito et al, 2006;Akhtar et al, 2007). The term 'primary progressive' (which also includes patients who progress within 3 months of their remission) has been used interchangeably with 'primary refractory' by some authors.…”