The Development of Hematopoietic Stem Cell Transplantation (HSCT) in Patients with Chronic Myeloid Leukemia (CML), in First Chronic Phase (CP), with HLA Identical Siblings Donors at the Bone Marrow Transplantation Unity–Jau, São Paulo/Brazil and Regional Cooperative Group
Authors: Colturato Vergilio Antônio Rensi , de Souza Mair Pedro , Mauad Marcos Augusto , de Azevedo Wellington Morais , de Mattos Éderson Roberto , Machado Clarisse Martins , Pontes Érica R. , Voltarelli Júlio C. , Simoes Belinda , Paton Eduardo J. A. , de Abreu Machado Paulo Eduardo 
Published: April 2020

Abstract
Since August 1996, we have perfomed 206 hematopoietic stem cell transplantations (HSCT) in patients with Chronic Myeloid Leukemia (CML). The number of procedures has been progressively lower since 2006, consequence of the results of ÍRIS Study (Imatinib in 1a line for patients with CML–1a CP). In 2007, we did 15 transplants. Among them, 26% didn’t have access to Imatinib, against 70% of 31 patients who were transplanted in 2004. During the last twelve years, we transplanted 163 patients in 1a CP that have presented survival probability curve of 80% and median follow up of 1.204 days. The patients ≤ 30 years old (n=29), that were already submitted to transplant, more than five years ago, presented survival rate of 93%, just a little bit superior to the 89% observed in the ÍRIS Study. In this group of patients, we observed two obits (1–acute Graft versus Host Disease, a-GVHD; 1–chronic Graft versus Host Disease, c-GVHD;), three relapses, all of them are alives and in complete cytogenetic remission, 15 patients developed c–GVHD, most of them were extensive, three of them remain in lengthened immunossuppression. On December, 2003, the patients with CML–1a CP, with age &gt; 30 years old, presented survival rate statistically inferior, than the patients with age ≤ 30 years old, using as myeloablative conditioning oral Busulfan without serum monitoring, BU (16 mg/kg), and Cyclosphophamide, CY, (120 mg/m2), due to higher transplanted related mortality (TRM = 29,2%) verified in the first group, against 6% verified in the second group. Since this date, the introduction of the association oral BU, without serum monitoring (16 mg/kg) and Fludarabine, FLU, (120 mg/m2) BU-FLU, n = 49, determined that the patients with higher age, median = 43 years old, showed similar survival rate with the group with lower age, n = 56 and median = 29 years old, that used BUCY, in the same period, 83% versus 85%, respectively, with median follow up of 877 days, consequence of lower TRM = 6,1%, observed in the BU-FLU group, after migration from historical BUCY group. Since 1996, the monitoring of BCR-ABL transcript, by molecular biology techniques, has provided the induction of cytogenetic evaluation realization, allowing that 72% from the 23 patients that relapsed in CP, from the 163 transplanted in CP, were detected in cytogenetics relapse. The 23 patients are alives: 14 already completed one year of relapse, among them, 13 are in complete cytogenetic remission (CCR). One patient, 16 years old, was submitted to a 2° HSCT and is in hematological remission. At this, in our service, the patients with CML in 1a CP, have indication to use Imatinib in 1a first line, even those &lt; 30 years old, due to the toxicity related to HSCT, mostly due to the high incidence of c-GVHD, with the exception of children below 18 years old, who don’t have access to Imatinib at Brazil. The older patients, conditioned with BLU-FLU, median age of 43 years old, have today a similar survival rate probability to the younger patients submitted to BUCY. Besides that, the monitoring by molecular biology techniques of BCR-ABL transcript, has provided us to diagnose a high rate of cytogenetic relapse, which has contributed for a good therapeutic result. This way, the HSCT with identical sibling donor remains being an adequate alternative, for the obtainment of a prolonged survival rate in patients with CML in 1 a CP, and should be considered, mainly in young patients, in case of unsuccess in using Imatinib, as long as adjustments on the conditioning of patients with higher age be done as well as the monitoring by molecular biology techniques of BCR-ABL transcript.