Haploidentical Allogeneic Stem Cell Transplantation in Poor Risk Cytogenetic Acute Myeloide Leukemia: Results in 33 Patients
Authors: Sala Elisa , Salama Mohamed Rasha , Carrabba Matteo Giovanni , Messina Carlo , Lupo Stanghellini Maria Teresa , Vago Luca , Pavesi Francesca , Morelli Mara , Marktel Sarah , Assanelli Andrea , Corti Consuelo , Peccatori Jacopo , Bernardi Massimo , Ciceri Fabio 
Published: October 2019

Abstract
Introduction
Complex Karyotype (CK), monosomy of chromosome 7 or 5 and Monosomal Karyotype (MK) are associated with a dismal outcome in Acute Myeloid Leukemia (AML) patients (pts). Allogeneic stem cell transplantation (allo-SCT) can be considered the only potentially curative option for these pts. Conventional allo-SCT strategies confer long term Overall Survival (OS) of around 20%. No data are available on the role of haploidentical stem cell transplantation (haplo-SCT) in this high risk setting. We reviewed our experience to address this issue.
Patients and methods
This retrospective analysis included adult AML pts treated at San Raffaele Hospital. Between November 2001 and April 2014, 33 consecutive pts with poor cytogenetic risk AML with monosomy of chromosome 7 or 5 (12/33 pts), MK (3/33 pts) and CK (18/33 pts) received haplo-SCT. Karyotypes were obtained from diagnostic bone marrow samples with standard methods and in accordance with International System of Human Cytogenetic Nomenclature guidelines. OS and Disease Free Survival (DFS) were calculated using the Kaplan-Meier product-limit method.
Results
Median age of pts at transplant was 50 years (range, 22 to 65). At the time of haplo-SCT, 10 pts (30%) were in complete remission (8 were in first complete remission), while 23 (70%) had active disease. Patients received a myeloablative conditioning regimen, Treosulfan-based. Twenty seven out of 33 pts received a T-cell repleted haplo-SCT, 6 pts a T-cell depleted haplo-SCT. In those pts who received a T-cell repleted transplant, GvHD prophylaxis was based on Cyclosporin and Methotrexate (7/27 cases) or Rapamycine and Mycophenolate Mofetil (20/27 cases). All 27 pts received Antithymocyte Globulin. Median follow-up after haplo-SCT was 304 days (range, 5 to 2897 days). Of 33 pts, 30 (91%) were in CR at day +30 after transplant, 1 died of sepsis before disease evaluation, 2 had disease persistence. At the last follow-up 11 out of 33 pts (34%) were alive, all of whom in CR, 22 pts (66%) died for the following causes: disease relapse/progression 10 (45%), Graft versus Host Disease 3 (14%), infection 9 (41%). Transplant related mortality (TRM) was 35.2% at 1 year and 35.2% at 3 years after transplant. Extimated DFS from day 30 after transplant was 34.5% at 1 year and 28% at 3 years. Extimated OS for all pts was 45% at 1 year and 22.6% at 3 years.
Discussion
Our data support haplo-SCT as a potentially curative option for AML pts with high risk cytogenetic abnormalities. Despite a TRM of 35% at 3 years, 1/3 of these pts achieved a long term disease free status. In the setting of a disease with extremely poor therapeutic options, haplo-SCT appears promising and not inferior to other sources of allogeneic stem cell transplantation. Transplantation strategies aimed at reducing transplant related mortality or disease relapse should be explored in order to improve these results and achieve a better outcome.

Disclosures
No relevant conflicts of interest to declare.