Severe Hypofunction of Allogeneic Hematopoietic Stem Cell Transplant in Patients with Oncohematological Diseases: Incidence, Risk Factors, and Outcomes

BONE MARROW TRANSPLANTATION ,

TA Rudakova, AD Kulagin, OU Klimova, IK Golubovskaya, EI Darskaya, TA Bykova, AG Smirnova, EV Morozova, SN Bondarenko, IS Moiseev, AV Beinarovich, DE Pevtsov, AL Alyanskii, EV Babenko, IM Barkhatov, BV Afanas’ev

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Tat’yana Aleksandrovna Rudakova, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; e-mail: t_a_rudakova@mail.ru

For citation: Rudakova TA, Kulagin AD, Klimova OU, et al. Severe Hypofunction of Allogeneic Hematopoietic Stem Cell Transplant in Patients with Oncohematological Diseases: Incidence, Risk Factors, and Outcomes. Clinical oncohematology. 2019;12(3):309–18 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-309-318

ABSTRACT

Aim. Based on strict criteria, to assess incidence, pretransplantation risk factors, and outcomes of severe hypofunction of graft, i.e. poor graft function (sPGF), following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults.

Materials & Methods. The trial included 710 adult patients (median age was 31 years, range 18–70 years; 55 % male and 45 % female patients) with different hematological diseases and documented transplant engraftment after allo-HSCT from matched sibling (20 %), unrelated (67 %) and haploidentical (13 %) donors in the period from 2008 to 2016. Myeloablative and reduced-intensity conditioning regimens were administered in 30 % and 70 % of patients, respectively. The analysis was based on the following sPGF criteria: 2 or more lines of cytopenia (thrombocytes < 20 × 109/L, absolute neutrophil count < 0.5 × 109/L, and hemoglobin < 70 g/L at any time after documented engraftment), complete or stable mixed donor chimerism > 90 %, and absence of relapse signs, rejection, and severe acute graft-versus-host reaction. The following factors were analyzed: age, sex, diagnosis, presence/absence of remission in acute leukemias, ferritin level, type of donor, HLA-match, blood group and sex match, transplant origin, number of transplanted CD34+ cells, and conditioning regimen. Multivariate analysis included parameters of univariate analysis with p < 0.05.

Results. After allo-HSCT sPGF was identified in 103 patients with 2-year cumulative incidence of 15 % (95% confidence interval [95% CI] 12–18 %). In most cases sPGF developed during the 1st year after allo-HSCT (median 50 days). Bi- and trilineage cytopenia was found in 59 % and 41 % of cases, respectively. In multivariate analysis sPGF risk was associated with myelodysplastic syndrome, myeloproliferative disorders (hazard ratio [HR] 3.403; 95% CI 1.972–5.606; p < 0.0001), and haploidentical donors (HR 3.830; 95% CI 1.545–8.828; p = 0.001). The absence of remission at the time of allo-HSCT in acute leukemias and blood group incompatibility were of borderline significance. In 50 % of cases sPGF determined poor outcome, including death from cytopenia-related complications, further relapses, and graft rejection. Prognosis of bilineage sPGF was slightly more favorable than that of trilineage sPGF.

Conclusion. The present large cohort trial yielded the incidence and analyzed the structure of sPGF in adult patients with oncohematological diseases. In addition, the key pretransplantation sPGF risk factors were identified. The results of the trial can serve to optimize the choice of therapy after allo-HSCT.

Keywords: allogeneic hematopoietic stem cell transplantation, poor graft function.

Received: March 6, 2018

Accepted: June 20, 2019

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