Modified conditioning regimen busulfan-cyclophosphamide followed by allogeneic stem cell transplantation in patients with multiple myeloma

Background Allogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma.The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently themajor limitation to wider use of this potentially curative treatment modality.The challenge for clinical investigators is toreduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem celltransplantion for multiple myeloma.In this study the toxicity and efficacy of modified myeloablative conditioning regimenfollowed by allogeneic stem cell transplantation was investigated in patients with multiple myeloma.Methods The conditioning regimen consisted of hydroxyurea,cytarabine,busulfan,cyclophosphamide,and semustine.Ten patients underwent allogeneic transplantation among them hydroxyurea （40 mg/kg） was administered twice on day-10 and cytarabine （2 g/m） was given on day-9,busulfan was administered orally in four divided doses daily for 3 days（days-8 to-6）.The dose of busulfan was 12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1hour on days-5 and-4 （1.8 g/m）,and with semustine （Me-CCNU） 250 mg/mon day-3.Results Chimerism data were available on all patients and all patients achieved full donor chimerism without graftfailure.Six patients had not acute graft-versus-host disease （GVHD,36.4%;95% Cl:13.9%-38.6%）.Two patients（18.2%） developed grade Ⅰ acute GVHD （95% Cl:10.9%-35.9%） and grade Ⅱ acute GVHD occurred in one patient （9.1%;95% Cl:8.4%-32.3%）.Severe grade IVa GVHD was seen in one patient,who died from acute GVHD.The incidence ofchronic GVHD was 22.2% （95% Cl:11.7%-36.7%）,among them one died of severe grade Ⅳ GVHD and one developedmultiorgan failure on day +170;the treatment-related mortality was 22.0% （95% Cl:10.3%-34.1%）.The overall 4-yearsurvival rate was 67.8% （95% Cl:16.3%-46.7%）.The estimated 4-year progression-free survival rate was 58.5% （95%Cl:13.7%-41.8%）.The 4-year complete remission was 72.7% （95% Cl:27.8%-49.6%）.One patient relapsed after 4months and achived the complete remission after receiving the donor lymphocyte infusion.Conclusions Modified conditioning regimen busulfan-cyclophosphamide with peripheral blood stem cells+bonemarrow cells transplantation result in a low incidence of severe GVHD with a relatively low treatment-related mortality,high complete remission rates and a long-term survival.