Idarubicin-intensified haploidentical HSCT with GvHD prophylaxis of ATG and basiliximab provides comparable results to sibling donors in high-risk acute leukemia

Abstract

We designed a novel haploidentical hematopoietic stem cell transplantation (haplo-HSCT) system using idarubicin (IDA) intensified conditioning regimens and combination of antithymocyte globulin and basiliximab for GvHD prophylaxis. The outcomes of 110 high-risk acute leukemia patients undergoing haplo-HSCT were compared with 69 contemporaneous high-risk patients receiving HLA-matched sibling transplantation using uniform IDA-intensified regimens. The relapse incidence of haplo-HSCT was 23.4%, and 3-year overall survival (OS) and disease-free survival (DFS) achieved 62.9%, 59.1%, respectively. The cumulative incidences of II-IV and III-IV aGvHD were 28.6 and 14.3%, while limited and extensive cGvHD were 19.4, 13.8%. All these results were equivalent to those of concurrent identical sibling transplantation. Three-year OS and DFS for patients in advance stage reached 48.5, 47.3%. Furthermore, the relapse, 3-year OS of positive minimal residual disease (MRD) patients did not differ from negative MRD patients (18.9% vs 11.5%, 63.6% vs 69.6%), indicating our intensified haplo-HSCT technique could circumvent the dismal prognosis of MRD. These data provide reinforcing evidence that our haplo-HSCT system could dramatically improve the survival of high-risk acute leukemia with low relapse and acceptable transplantation-related mortality, and might be a promising therapeutic option for high-risk patients.

Idarubicin-Intensified Hematopoietic Cell Transplantation Improves Relapse and Survival of High-Risk Acute Leukemia Patients with Minimal Residual Disease

“…A cohort of 98 consecutive patients with high-risk acute leukemia who underwent their first allo-HSCT using IDA-intensified conditioning regimens from January 2012 to January 2017 at the Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, were included in this retrospective study. We classified patients as high risk at diagnosis following the criteria in our previous reports [9][10][11][12]. The definition of high-risk AML were no response to induction chemotherapy, relapse within 6 months after induction or consolidation therapy, relapse within 6 months after induction therapy that could not be relieved using the original induction therapy, 2 relapses or relapse after auto-HSCT, unfavorable cytogenetics, or a history of preceding neoplasia and/or chemotherapy in no remission (NR).…”

“…The definition of hematopoietic engraftment was similar to that reported previously [9][10][11][12]. Chimerism was typically evaluated in recipient BM or whole peripheral blood without separation usually on days +30, +90, +180, +270, and +360 after transplantation.…”

“…Institutional standard antimicrobial prophylaxis covering fungal and bacterial agents were administered in all patients [9][10][11][12]. Cytomegalovirus (CMV) monitoring was performed once a week using a RT Taqman CMV DNA PCR until day 100 after allo-HSCT, then once every 2 weeks until day 180, followed by once every month until 1 year after HSCT.…”

“…In HLA-matched related or unrelated allo-HSCT for acute leukemia, several studies have reported a dose-dependent effect of the intensity of the conditioning regimen on disease control. In our previous studies, we demonstrated that allo-HSCT using idarubicin (IDA)-intensified conditioning regimens could reduce relapse of high-risk acute leukemia patients, which translated into improved survival [9][10][11][12]. One might anticipate that the intensity of the preparative regimen would be of greater importance in patients with MRD because more effective leukemic cell clearance and deeper molecular response are potentially achievable with intensified conditioning regimen for these high-risk patients.…”

The consensus on indications, conditioning regimen, and donor selection of allogeneic hematopoietic cell transplantation for hematological diseases in China—recommendations from the Chinese Society of Hematology

“…Lie et al used a combination of fludarabine, cytarabine, TBI, Cy, and etoposide for conditioning in the haplo-setting and demonstrated that intensified conditioning decreased the 5-year relapse rate from 33.9 to 27.3%, and it may be a better approach for refractory and acute leukemia of ambiguous lineage [ 84 – 86 ]. Idarubicin-intensified haplo-HSCT introduced by the Wuhan Union group improved the dismal prognosis of pre-transplant MRD and yielded a 3-year DFS of 47.3% [ 87 ].…”