Long-term outcomes of ruxolitinib therapy in steroid-refractory graft-versus-host disease in children and adults.

Acute and chronic steroid-refractory graft-versus-host disease (srGVHD) is a life-threatening complication of allogeneic stem cell transplantation. There are a number of reports on case series describing efficacy of ruxolitinib in both acute and chronic srGVHD. We conducted a prospective study (NCT02997280) in 75 patients with srGVHD (32 acute, 43 chronic, 41 adults, and 34 children). Patients with chronic GVHD had severe disease in 83% of cases, and acute GVHD patients had grade III-IV disease in 66% of cases. The overall response rate (ORR) was 75% (95% CI 57-89%) in acute GVHD and 81% (95% CI 67-92%) in chronic. Overall survival was 59% (95% CI 49-74%) in acute group and 85% (95% CI 70-93%). The major risk factors for lower survival were grade III-IV gastrointestinal involvement (29% vs 93%, p = 0.0001) in acute form and high disease risk score in chronic (65% vs 90%, p = 0.038). Toxicity was predominantly hematologic with 79% and 44% of grade III-IV neutropenia in acute and chronic groups, respectively. There was no difference between adults and children in terms of ORR (p = 0.31, p = 0.35), survival (p = 0.44, p = 0.12) and toxicity (p > 0.93). The study demonstrated that ruxolitinib is an effective option in acute and chronic srGVHD and can be used both in adults and children.

First experience of hematopoietic stem cell transplantation treatment of Shwachman-Diamond syndrome using unaffected HLA-matched sibling donor produced through preimplantation HLA typing.

The only proven cure for Shwachman-Diamond syndrome (SDS) bone marrow failure is allogeneic hematopoietic stem cell transplantation (HSCT). However HSCT with donors other than HLA-identical siblings is associated with high mortality and unfavorable prognosis. This paper presents the first experience of HSCT treatment of SDS using an unaffected HLA-identical sibling produced through preimplantation genetic diagnosis (PGD). The patient was a 6-year-old blood transfusion-dependent SDS baby girl with secondary myelodysplastic syndrome, for whom no HLA-identical donor was available. As a result of PGD, two unaffected HLA matched embryos were identified; one of them was randomly selected for transfer, resulting in a clinical pregnancy and birth of an apparently healthy child. The patient underwent allogeneic transplantation of cord blood hematopoietic stem cells, together with bone marrow from this sibling, resulting in complete hemopoietic recovery. The patient was no longer transfusion-dependent and had normal blood values 160 days after transplantation.

[Efficacy of donor lymphocyte infusion in patients after different types of allogeneic hematopoietic stem cell transplantation].

AIM: To evaluate the efficacy of donor lymphocyte infusion (DLI) to prevent and treat recurrences in patients after different types of allogeneic hematopoietic stem cell transplantation (allo-HSCT). SUBJECTS AND METHODS: Data from 118 patients with malignant blood diseases were analyzed. Allo-HSCTs from HLA-matched related donors (n=49), HLA-matched unrelated donors (n=50), partially HLA-matched unrelated donors (n=2), and haploidentical donors (n=24) were performed. The indications for DLI were underlying disease relapse (59 DLIs), resistant disease course (n=40), minimal residual disease (n=1 6), falling donor chimerism (n=1 5), and recurrence prevention (n=1 3). RESULTS: Therapy response was obtained after 57 (44%) DLls. There were 36 (25%) and 30 (21%) cases of acute and chronic graft-versus-host reactions (GVHR), respectively. The use of DLI from HLA-matched donors, its performance in the periods of D+100 to one year after allo-HSCT, a donor chimerism level of over 90% at the moment of DLI, the administration of the initial DLI dose of below 1.10(6) CD3+/kg, and the development of chronic GVHR after DLI were associated with the highest rate of therapy responses. The overall survival rates of patients with DLI were significantly influenced by factors, such as DLI periods, donor chimerism levels at DLI, and the development of chronic CVHR after DLI. CONCLUSION: The choice of the optimal dose of cells, the periods of DLI and its preventive administration improve prognosis in patients after allo-HSCT. The occurrence of acute GVHR is affected by the degree of HLA matching and the type of a donor. The development of chronic GVHR after DLI is associated with the highest rate of responses to DLI and higher survival rates.

[Invasive mycoses during hematopoietic stem cell transplantation].

AIM: To define the frequency, etiology, and risk factors of invasive mycoses (IM) in patients with allogeneic (allo) and autologous (auto) hematopoietic stem cell transplantation (HSCT) and to evaluate the impact of IM on overall survival (OS). MATERIALS AND METHODS: Data on 356 patients after allo-HSCT (n = 237) and auto-HSCT (n = 119) from 2000 to 2010 were analyzed. The diagnosis of IM was established according to the EORTC/MSG 2008 criteria. RESULTS: The incidence of myocardial infarction (MI) was 19.1%; that was 23.2 and 10.9% in allo-HSCT and auto-HSCT recipients, respectively. The incidence of MI following allo-HSCT was significantly higher than that after auto-HSCT. Aspergillus spp. (82.3%), Candida spp. (11.8%), zygomycetes (Mucor spp., Rhizopus spp.) (4.4%), and Cryptococcus neoformans (1.5%) are involved in the etiology of MI. Its risk factors are acute lymphoblastic leukemia; non-myeloablative conditioning regimen; use of fludarabine and antilymphocyte globulin; peripheral blood stem cells as a source for grafting; long-term lymphopenia, neutropenia; use of granulocyte colony-stimulating factor (G-CSF); acute graft-versus-host reaction; grade 3-4 mucositis; infections, such as cytomegalovirus, sepsis. The development of MI in HSCT recipients did not significantly reduce one-year OS after allo-HSCT and auto-HSCT--53.6 and 55% and 86.7 and 90.3% (with and without MI, respectively). In patients with invasive aspergillosis, OS (12 weeks after IM being diagnosed) was significantly longer in those with other invasive mycoses (91.3 and 50%, respectively). CONCLUSION: The incidence of MI after allo-HSCT was higher than that after auto-HSCT. MI induced by the fungal genus Aspergillus spp. was most common. Along with known risk factors, there was a poor prognostic factor, such as G-CSF. The development of MI failed to affect one-year OS, which was indicative of the adequate quality of its early diagnosis and therapy. The prognosis was poor in patients with invasive candidiasis, zygomycosis, and cryptococcosis. Investigations need to be continued to specify the reasons for high morbidity rates and the factors provoking discussion by investigators worldwide.