Hairy cell leukemia (HCL) is a rare, low-grade mature B-cell neoplasm with a characteristic clinical, morphological, immunophenotypic, and more recently described molecular (BRAF p.V600E mutation) profile. It typically affects middle-aged to elderly male who present with pancytopenia and massive splenomegaly. Lymphadenopathy is usually not seen. Atypical presentations such as absence of splenomegaly and presence of lymphadenopathy and leukocytosis, a hypoplastic marrow masquerading as aplastic anemia, pose a diagnostic challenge to both clinician and pathologist. A diligent morphological examination to look for the presence of hairy cells along with flow cytometric immunophenotyping showing consistent bright expression of CD200, in addition to well-described characteristic immunophenotype, helps in correctly diagnosing the case. This can be further confirmed by the consistent presence of V600E point mutation in BRAF gene. The correct identification of HCL in these unusual clinical presentations is of utmost importance owing to a different treatment approach in these cases. We present here four such cases with atypical presentation.

Increasing evidence has emerged lately regarding the use of autologous hematopoietic stem cell transplantation (HSCT) in the treatment of aggressive multiple sclerosis (MS). However, data is scarce regarding the use of allogenic HSCT in treating MS. We present a 42 years old male with aplastic anemia who underwent allogenic HSCT for severe aplastic anemia. This patient was diagnosed with primary progressive multiple sclerosis (PPMS) one-year post transplant and had to undergo a second HSCT due to his hematological disorder. His second HSCT was conditioned with an alemtuzumab containing regimen, after which his MRI and expanded disability status scale (EDSS) remained to be stable for 18 months.

We report on 499 patients with severe aplastic anemia aged ≥50 years who underwent hematopoietic cell transplantation (HCT) from HLA-matched sibling (n=275), or HLA-matched (8/8) unrelated donors (n=39187) between 2005 and 2016. The median age at HCT was 57.8 years; 16% of patients were 65-77 years old. Multivariable analysis confirmed higher mortality risks for patients with performance score less than 90% (HR 1.41 (1.03-1.92), p=0.03) and after unrelated donor transplantation (HR 1.47 (1-2.16), p=0.05). The 3-year probabilities of survival for patients with performance score 90-100 and less than 90 after HLA-matched sibling transplant were 66% (57-75%) and 57% (47-76%), respectively. The corresponding probabilities after HLA-matched unrelated donor transplantation were 57% (48-67%) and 48% (36-59%). Age at transplantation was not associated with survival but grade II-IV acute GVHD risks were higher for patients aged 65 years or older (sHR 1.7 (1.07-2.72), p=0.026). Chronic GVHD was lower with GVHD prophylaxis regimens calcineurin inhibitor (CNI) + methotrexate (sHR 0.52 (0.33-0.81), p=0.004) and CNI alone or other agents (sHR 0.27 (0.14-0.53), p<0.001) compared to CNI + mycophenolate. While donor availability is modifiable only to a limited extent, choice of GVHD prophylaxis and selection of patients with good performance scores are key for improved outcomes.

Allogeneic hematopoietic stem cell transplantation (HSCT) is currently successfully used in the treatment of many non-malignant hematopoietic disorders, including acquired and inherited bone marrow failure. HSCT from a HLA-identical sibling donor (MSD) is the treatment of choice, better results are achieved using bone marrow graft. Conditioning regimens and graft-versus-host disease prophylaxis are different in dependence on the underlying disease, age and clinical condition of the patient, type of donor and stem cell graft. Transplantation from MSD is the first-line treatment for children and young adults with SAA. Patients with hemoglobinopathies and inherited bone marrow failure syndromes with available MSD should be referred for transplantation as soon as possible, before the development of serious complications and iron overload-related tissue damage. Indications for HSCT from matched unrelated donor in the treatment of non-malignant hematopoietic disorders are expanding in dependence on very good results in the last two decades. The aim of successfully HSCT is not only to increase the percentage of surviving patients but also to improve the quality of life with the minimum of early complications and late effects. Key words: allogeneic hematopoietic stem cell transplantation - aplastic anemia - hemoglobinopathy - inherited bone marrow failure.

Aplastic anemia - bone marrow failure (AA) is defined as pancytopenia with hypocellular bone marrow without signs of marrow fibrosis or of presence of abnormal cells. Recent studies showed that most of AA cases might be mediated by immune mechanisms. Toxic agent leads to expression of neoantigens or cryptic antigens on the surface of pluripotent hematopoietic stem cells with subsequent activation of immune effector cells and induction of stem cell apoptosis. Histopathological findings obtained from bone marrow biopsy are crucial for diagnosis of AA. Hypoplastic MDS, PNH, hairy cell leukemia and late manifestation of congenital cytopenias must be excluded in differential diagnosis. Allogeneic stem cell transplantation from HLA matched related donor or combined immune suppression represent the first line treatment for patients with severe AA (SAA). Transplantation from unrelated donor may be a second line treatment for patients who failed to respond to immunosuppressive therapy. Recent studies showed eltrombopag or its combination with immune supression as an effective therapeutic approach to AA patients. Up to 15 % of AA patients may later develop PNH, MDS or acute leukemia. An influence of disturbed immune mechanisms as well as of immunosuppressive treatment on the development of clonal proliferation is currently discussed.  Key words: aplastic anemia - diagnosis - eltrombopag - immunosuppression - transplantation - treatment.

Objective: To evaluate the outcome of combination of haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) with an unrelated cord blood unit for severe aplastic anemia (SAA). Methods: The clinical data of 127 SAA patients [including 74 male and 53 female patients, 65 very severe aplastic anemia (vSAA), the median age as 23.5(3-54) years] received HID-HSCT from September 2011 to April 2017 were analyzed retrospectively. The median interval from SAA diagnosis to transplantation was 2 (0.5-180) months. The conditioning was modified Bu/Cy+ATG/ALG-based (Busulfan + cyclophosphamide + antithymocyte immunoglobulin/antilymphocyte immunoglobulin) regimen. Cord blood units were selected based on the results of HLA typing and cell doses evaluated before freezing. Units with at least 4/6 matched HLA loci became the candidates. Prophylaxis for graft-versus host disease (GVHD) was by cyclosporine (CsA), mycophenolate mofetil (MMF) plus short-term methotrexate (MTX). Results: The median values of absolute nucleated cell counts were 10.87 (3.61-24.00)×10(8)/kg in the haploidentical grafts and 2.22 (1.10-7.30)×10(7)/kg in the cord blood units, respectively. The median doses of CD34(+) cells infused were 3.49(1.02-8.89) ×10(6)/kg in the haploidentical grafts and 0.56 (0.16-2.27) ×10(5)/kg in the cord blood units, respectively. Of the 127 patients, 5 patients occurred early death, one patient occurred primary graft failure. All 121 surviving patients attained complete haploidentical engraftment. The median durations of myeloid engraftment were 11 (9-28) days and 15 (9-330) days for platelets, with a cumulative platelet engraftment incidence of 96.1%. The incidence of infection was 58.27% (74/127). During a median follow-up of 20.5 (4-60) months, the incidence of grade Ⅱ-Ⅳ acute GVHD was 24.79% (30/121), moderate-severe chronic GVHD was 14.15% (15/106), 4-year estimated overall survival was (78.5±4.3) %, 4-year estimated failure-free survival was (77.4±4.3) %, respectively. Conclusion: Combination of HID-HSCT and an unrelated umbilical cord blood unit was a feasible choice with favorable outcome for SAA patients without matched donors.