Autologous hematopoietic stem cell transplantation conditioning regimens and chimeric antigen receptor T cell therapy in various diseases

Conditioning regimens employed in autologous stem cell transplantation have been proven useful in various hematological disorders and underlying malignancies;however,despite being efficacious in various instances,negative consequences have also been recorded.Multiple conditioning regimens were extracted from various literature searches from databases like PubMed,Google scholar,EMBASE,and Cochrane.Conditioning regimens for each disease were compared by using various end points such as overall survival(OS),progression free survival(PFS),and leukemia free survival(LFS).Variables were presented on graphs and analyzed to conclude a more efficacious conditioning regimen.In multiple myeloma,the most effective regimen was high dose melphalan(MEL)given at a dose of 200/mg/m2.The comparative results of acute myeloid leukemia were presented and the regimens that proved to be at an admirable position were busulfan(BU)+MEL regarding OS and BU+VP16 regarding LFS.In case of acute lymphoblastic leukemia(ALL),BU,fludarabine,and etoposide(BuFluVP)conferred good disease control not only with a paramount improvement in survival rate but also low risk of recurrence.However,for ALL,chimeric antigen receptor(CAR)T cell therapy was preferred in the context of better OS and LFS.With respect to Hodgkin’s lymphoma,mitoxantrone(MITO)/MEL overtook carmustine,VP16,cytarabine,and MEL in view of PFS and vice versa regarding OS.Non-Hodgkin’s lymphoma patients were administered MITO(60 mg/m2)and MEL(180 mg/m2)which showed promising results.Lastly,amyloidosis was considered,and the regimen that proved to be competent was MEL 200(200 mg/m2).This review article demonstrates a comparison between various conditioning regimens employed in different diseases.

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 the major limitation to wider use of this potentially curative treatment modality. The challenge for clinical investigators is to reduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem cell transplantion for multiple myeloma. In this study the toxicity and efficacy of modified myeloablative conditioning regimen followed 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/ms） 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 1 hour on days -5 and -4 （1.8 g/m^2）, and with semustine （Me-CCNU） 250 mg/m^2 on day -3. Results Chimerism data were available on all patients and all patients achieved full donor chimerism without graft failure. Six patients had not acute graft-versus-host disease （GVHD, 36.4%; 95% CI： 13.9%-38.6%）. Two patients （18.2%） developed grade Ⅰ acute GVHD （95% CI： 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 of chronic GVHD was 22.2% （95% Cl： 11.7%-36.7%）, among them one died of severe grade IV GVHD and one developed multiorgan failure on day ＋170; the treatment-related mortality was 22.0% （95% Cl： 10.3%-34.1%）. The overall 4-year survival rate was 67.8% （95% Cl： 16.3%-46.7%）. The estimated 4-year progression-free survival rate was 58.5% （95% CI： 13.7%-41.8%）. The 4-year complete remission was 72.7% （95% CI： 27.8%-49.6%）. One patient relapsed after 4 months and achived the complete remission after receiving the donor lymphocyte infusion. Conclusions Modified conditioning regimen busulfan-cyclophosphamide with peripheral blood stem cells＋bone marrow 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.