Hematopoietic stem cell transplantation with alpha/beta T-lymphocyte depletion and short course of eculizumab in adolescents and young adults with paroxysmal nocturnal hemoglobinuria

The main goal is to optimize hematopoietic stem cell transplantation (HSCT) approach among adolescents and young adults with paroxysmal nocturnal hemoglobinuria (PNH) by means of Graft-versus-host disease (GVHD) and post-transplant complications risk lowering. Materials and methods. We report our experience of HSCT from HLA-matched unrelated donors using TCR alfa/beta and CD19 depletion in 5 pts (1M/4F) with PNH, developed after successful immunosuppressive therapy (IST) of acquired aplastic anemia (AA). Median age of pts at the moment of transplantation was 17,8 years (range 14,5-22,7), median interval from IST to PNH was 4 years (5mo - 6,5 y). In all patients non-severe pancytopenia was present: granulocytes 0,8х109/l (0,8-1,8 х109/l) platelets 106 х109/l (27-143 х109/l) and Hb -78 g/l, median PNH clone size in granulocytes was 94 (range 75-99)%. One pts previously developed sinus thrombosis. Conditioning consisted of thoraco-abdominal irradiation 4-6 Gy, cyclophosphamide 100 mg/kg, fludarabine 150 mg/m2 and anti-thymocyte globulin (ATG) or alemtuzumab. Eculizumab was given from day (-7) till day (+14) (every 7 days, only 4 times). GVHD prophylaxis was tacrolimus ± methotrexate. Results. Infusedgraft characteristics were: CD34+ - 8,1х106/kg, CD3TCRab·150х103/kg, CD3gd+ - 7,3х106/kg, СD19+ - 221х103/kg, NK -6,4х108/kg. Engraftment was achieved in all 5 pts with a median of 15(12-18) и 13(10-18) days for granulocytes and platelets, respectively. Skin acute GVHD grade I developed in only 1 pt, and subsided with short course of glucocorticoids. CMV reactivation occurred in 1 pt; there were no episodes of Epstein-Barr Virus (EBV) o rAdenovirus (AdV) reactivation. Full donor myeloid chimerism was established in all pts by day +30. Immune reconstitution was delayed until 6 months after transplant but no severe infections occurred. All pts are alive 1,7-5,5 years (med 4 years) after HSCT with normal hematopoiesis and immune function, full donor chimerism and no late sequelae. Conclusions. Transplantation of TCRalfa/beta and CD19 depleted hematopoietic cells from matched unrelated donor after immunoablative conditioning and supported with short course of eculizumab is perfectly safe and efficient technology leading to cure in young patients with PNH

The role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia: literature review and own experience

Aim. The analysis of experience of nelarabine use in refractory/relapsed T-cell acute lymphoblastic leukemia (T-ALL) depending on the immunophenotype and the line of therapy. Materials and methods. All the patients with relapsed or refractory T-ALL aged from 0 to 18 years who received treatment with nelarabine as a part of the therapeutic element R6 were included in the study. For all patients a detailed immunological analysis of leukemia cells with discrimination of immunological variants TI, TII, TIII or TIV was performed. Patients administered with nelarabine as a first therapeutic element were referred to the first-line therapy group, other patients were referred to the second-line therapy group. Nelarabine was administered as intravenous infusion at a dose of 650 mg/m2, on days 1-5. Allogeneic hematopoietic stem cells transplantation (allo-HSCT) was considered for all patients. Results. From 2009 to 2017, 54 patients with refractory/relapsed T-ALL were treated with nelarabine. Five-year event-free survival (EFS) and overall survival (OS) was 28% for all patients, cumulative risk of relapse (CIR) was 27%. EFS was significantly higher in nelarabine first-line therapy group in comparison with second-line therapy group (34±8% vs 8±8%, p=0,05). In patients after allo-HSCT EFS, OS and CIR were 51±10%, 50±10% and 39,1±9,5% accordingly. The best results were achieved in patients with TI immunophenotype. No toxicity-related mortality as well as severe neurologic complications or discontinuation of therapy associated with use of nelarabine were reported. Conclusion. The use of nelarabine is an effective strategy for the treatment of relapsed and refractory T-ALL. The best treatment outcomes were obtained in patients with TI immunophenotype and in the first-line therapy group. Optimal dosage regimens can be established during controlled clinical trials

Treatment of non-Hodgkin lymphoma and mature В-cell acute leukemia in children and adolescents: data of Russian regional hospitals

The article presents treatment results of 233 patients (children and adolescents under 19 years old; median — 8.76 years) with CD20-positive non-Hodgkin lymphomas and B-cell acute leukemia (B-NHL/B-AL) received chemotherapy (BFM B-NHL 90–95 protocols) or combined chemo-immunotherapy with rituximab (B-NHL-2004mab protocol). Combined chemo-immunotherapy was used for patients with Burkitt lymphoma, diffuse large cells lymphomas stage III–IV and B-AL, and included cytoreductive phase, 6 polychemotherapy (PCT) courses and rituximab. PCT courses are similar to those of original BFM B-NHL90 protocol, except for the first 2 courses, where daily methotrexate dose was reduced from 5 to 1 g/m2/24 h. Rituximab infused IV 12 hours before the start of first 4 chemotherapy courses at a dose of 375 mg/m2. The data in the questionnaires form have been submitted from 28 pediatric specialized hospitals from 27 Russia regions over the past 5 years (2005–2009). Protocol with rituximab has proved to be more effective than chemotherapy alone. The authors discuss the possibility of using combined chemo-immunotherapy for the treatment of B-NHL/B-AL at regional hospitals and the prospects for further treatment results improvement in this group of tumors.</p

Epidemic outbreak of candidemia caused by unusual types of Candida non-albicans: clinical course patterns and search for the source

Introduction: Invasive fungal infections (IFI) remain an unresolved issue of hematology/oncology despite the introduction of methods of early diagnostic and invent of new highly active antimycotics. In etiologic structure of IFI the leading role belongs to candidiasis, the most frequent clinical form of which is candidemia. Candidemias in the pediatric hematology/oncology departments usually occur as sporadic cases, and epidemics are very rare. We describe an epidemic outbreak of candidemia caused by species of Candida non-albicans rarely reported in patients.Results: Ten cases of candidemia were registered in the hematology/oncology department within one month. Candidemia was caused by C. guilliermondi in 4 patients (in 1 concomitantly with C. calliculosa), by С. parapsilosis – in 3 patients and by C. pelliculosa in another 3 patients. Contaminated intravenous 4 % KCl solution has been found to be the source of candidemia. In four patients granulocytes count was &lt; 0.5 109/l at the time of positive blood cultures. Clinical manifestation of candidemia included fever &gt; 38.5 in all patients and lung involvement in 2 patients. All patients received systemic antifungal therapy: 5 — monotherapy, 3 — combinations of 2 drugs and 2 — of 3 drugs. Central venous catheter was removed in 4 patients. Clinical and microbiological cure was achieved in all patients; the mortality rate was 0 %. In 2 patients candidemia relapsed 22 and 60 days after the first episode.Conclusions: Outbreaks of systemic infections caused by unusual pathogens necessitate searching of a single infection source. Candidemia caused by a direct pathogen inoculation in the bloodstream, in the absence of multiple risk factors for invasive fungal infections follows a favorable course

Epidemic outbreak of candidemia caused by unusual types of Candida non-albicans: clinical course patterns and search for the source

Introduction: Invasive fungal infections (IFI) remain an unresolved issue of hematology/oncology despite the introduction of methods of early diagnostic and invent of new highly active antimycotics. In etiologic structure of IFI the leading role belongs to candidiasis, the most frequent clinical form of which is candidemia. Candidemias in the pediatric hematology/oncology departments usually occur as sporadic cases, and epidemics are very rare. We describe an epidemic outbreak of candidemia caused by species of Candida non-albicans rarely reported in patients.Results: Ten cases of candidemia were registered in the hematology/oncology department within one month. Candidemia was caused by C. guilliermondi in 4 patients (in 1 concomitantly with C. calliculosa), by С. parapsilosis – in 3 patients and by C. pelliculosa in another 3 patients. Contaminated intravenous 4 % KCl solution has been found to be the source of candidemia. In four patients granulocytes count was &lt; 0.5 109/l at the time of positive blood cultures. Clinical manifestation of candidemia included fever &gt; 38.5 in all patients and lung involvement in 2 patients. All patients received systemic antifungal therapy: 5 — monotherapy, 3 — combinations of 2 drugs and 2 — of 3 drugs. Central venous catheter was removed in 4 patients. Clinical and microbiological cure was achieved in all patients; the mortality rate was 0 %. In 2 patients candidemia relapsed 22 and 60 days after the first episode.Conclusions: Outbreaks of systemic infections caused by unusual pathogens necessitate searching of a single infection source. Candidemia caused by a direct pathogen inoculation in the bloodstream, in the absence of multiple risk factors for invasive fungal infections follows a favorable course.</p

Use of plerixafor for hematopoietic stem cells mobilization in allograft donors

Unsuccessful mobilization of hematopoietic stem cells (HSCs) before apheresis in allograft donor is a factor adversely affecting the characteristics of the obtained cell product and, as a consequence, the therapy outcome. This study investigates the efficacy and safety of plerixafor as an additional alternative drug for HSCs mobilization after nsuccessful mobilization using G-CSF. Mobilization of HSC in all cases was performed using a preparation of G-CSF during 5 days. The ineffectiveness of this in 17 donors was revealed on the fourth day from the beginning of the mobilization, and therefore plerixafor was administered to all donors in this cohort 11–12 hours before cytapheresis. Use of plerixafor allowed obtaining a transplant with good cellular characteristics in all cases. Plerixafor safety profile comparable with GCSF has also been demonstrated. Based on the results of this study it was concluded about efficacy and feasibility of plerixafor as “rescue” therapy after unsuccessful mobilizationwith G-CSF.</p