Acute myeloid leukaemia (AML) is a disorder characterized by a clonal proliferation derived from primitive haematopoietic stem cells or progenitor cells. Abnormal differentiation of myeloid cells results in a high level of immature malignant cells and fewer differentiated red blood cells, platelets and white blood cells. The disease occurs at all ages, but predominantly occurs in older people (>60 years of age). AML typically presents with a rapid onset of symptoms that are attributable to bone marrow failure and may be fatal within weeks or months when left untreated. The genomic landscape of AML has been determined and genetic instability is infrequent with a relatively small number of driver mutations. Mutations in genes involved in epigenetic regulation are common and are early events in leukaemogenesis. The subclassification of AML has been dependent on the morphology and cytogenetics of blood and bone marrow cells, but specific mutational analysis is now being incorporated. Improvements in treatment in younger patients over the past 35 years has largely been due to dose escalation and better supportive care. Allogeneic haematopoietic stem cell transplantation may be used to consolidate remission in those patients who are deemed to be at high risk of relapse. A plethora of new agents - including those targeted at specific biochemical pathways and immunotherapeutic approaches - are now in trial based on improved understanding of disease pathophysiology. These advances provide good grounds for optimism, although mortality remains high especially in older patients.

Acute myeloid leukaemia.

https://www.pnhdisease.org/html/files/diagnosis_and_management.pdf

Diagnosis and management of paroxysmal nocturnal hemoglobinuria.

Adipose tissue is now on the top one of stem cell sources regarding its accessibility, abundance, and less painful collection procedure when compared to other sources. The adipose derived stem cells (ADSCs) that it contains can be maintained and expanded in culture for long periods of time without losing their differentiation capacity, leading to large cell quantities being increasingly used in cell therapy purposes. Many reports showed that ADSCs-based cell therapy products demonstrated optimal efficacy and efficiency in some clinical indications for both autologous and allogeneic purposes, hence becoming considered as potential tools for replacing, repairing, and regenerating dead or damaged cells. In this review, we analyzed the therapeutic advancement of ADSCs in comparison to bone marrow (BM) and umbilical cord (UC)-mesenchymal stem cells (MSCs) and designed the specific requirements to their best clinical practices and safety. Our analysis was focused on the ADSCs, rather than the whole stromal vascular fraction (SVF) cell populations, to facilitate characterization that is related to their source of origins. Clinical outcomes improvement suggested that these cells hold great promise in stem cell-based therapies in neurodegenerative, cardiovascular, and auto-immunes diseases.

https://www.mdpi.com/1422-0067/20/10/2523/pdf

Regenerative Capacity of Adipose Derived Stem Cells (ADSCs), Comparison with Mesenchymal Stem Cells (MSCs).

Evans syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia (ITP) and autoimmune haemolytic anaemia (AIHA) with a positive direct antiglobulin test (DAT) in the absence of known underlying aetiology. This condition generally runs a chronic course and is characterised by frequent exacerbations and remissions. First-line therapy is usually corticosteroids and/or intravenous immunoglobulin, to which most patients respond; however, relapse is frequent. Options for second-line therapy include immunosuppressive drugs, especially ciclosporin or mycophenolate mofetil; vincristine; danazol or a combination of these agents. More recently a small number of patients have been treated with rituximab, which induces remission in the majority although such responses are often sustained for <12 months and the long-term effects in children are unclear. Splenectomy may also be considered although long-term remissions are less frequent than in uncomplicated ITP. For very severe and refractory cases stem cell transplantation (SCT) offers the only chance of long-term cure. The limited data available suggest that allogeneic SCT may be superior to autologous SCT but both carry risks of severe morbidity and of transplant-related mortality. Cure following reduced-intensity conditioning has now been reported and should be considered for younger patients in the context of controlled clinical trials.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2141.2005.05809.x

Management of Evans syndrome

Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study

We conducted a single-arm prospective study in 50 patients who received the combination of an haploidentical stem cell graft and an unrelated umbilical cord blood unit for the treatment of hematological malignancies. The median time for neutrophil engraftment was 13 days (11-20 days), and for platelets was 15 days (11-180 days). All surviving patients attained complete haploidentical engraftment except three patients who presented a mixed engraftment with increasing cord blood and decreasing haplo mismatch chimerism during the first 4 months after transplantation. The cumulative incidence of grade II-IV acute GVHD was 20%±0.327% at day+100, and the incidence of chronic GVHD was 19.26%±1.0% at 1 year. The 1-year cumulative incidence of relapse was 19.78%±1%, and the TRM was 16.2%±0.54%. At 1 year, overall survival was 78.6%±7.6% and PFS 64.0%±11.0%. The BU/CY-based conditional regimen showed a significant superiority over TBI/CY on PFS (relative risk=5.012, 95% confidence interval, 1.146-21.927, P=0.032). In conclusion, the co-infusion of an unrelated cord blood unit may potentially improve the outcome of haploidentical allogeneic hematopoietic SCT.

Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study

Background Myelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML). Methods Leukemic transformation in 151 patients with MDS was dynamically followed up. The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed. Results During the course of this study, over the past eight years and seven months, 21 (13. 91%) of 151 MDS patients progressed to overt leukemia, with a median interval of 5 (1 -23) months. There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups. Transformation occurred either gradually or rapidly. There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy. All of the 21 patients with leukemia suffered from MDS-AML, and most of them were M 2 , M 4 , or M 5 . Two (9. 52%) MDS-AML patients developed extramedullary infiltration. Leukopenia was found in 47. 62% of these patients. Two thirds of these patients, whose bone marrows were generally hypercellular, suffered from neutropenia. After developing AML, 8 (47. 06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD 3 3 [(49.83 ′ 24. 50)% ] , CD 1 3 [(36. 38 ′ 33. 84 ) % ], monocytic antigen CD 1 4 [ ( 38. 50 ′ 24. 60)%], and stem cell marker CD 3 4 [ ( 34. 67 ′ 30. 59 ) %], were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation. In some cases, lymphoid antigens, such as CD 5 , CD 7 , CD 9 , and CD 1 9 , coexisted with myeloid antigens. A low complete remission rate (31.25%) and a short survival time, with median survival of 6 (1 -28) months, were found in patients with MDS-AML treated by induction chemotherapy. Conclusions MDS has a high risk of developing into AML, either gradually or rapidly. Patients with MDS-AML have specific biological characteristics and a worse prognosis.

Transformation of myelodysplastic syndromes into acute myeloid leukemias.

Background: Biphenotypic acute leukemia (BAL) is a rare type of acute leukemia that presents with a high degree of heterogeneity and is not well defined. Methods:

Guangsheng He

Papers

Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study

Transformation of myelodysplastic syndromes into acute myeloid leukemias.

Clinical characteristics, biological profile, and outcome of biphenotypic acute leukemia: a case series.

The utility of fluorescence in situ hybridization analysis in diagnosing myelodysplastic syndromes is limited to cases with karyotype failure.

Cytomegalovirus Glycoprotein B Genotype in Hematopoietic Stem Cell Transplant Patients from China