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Introduction: For the majority of patients with acute myeloid leukemia (AML) an allogeneic stem cell transplant (SCT) in first complete remission (CR) is preferred. However, whether the number of courses required to achieve CR has a prognostic impact is unclear. It is unknown which factors remain important in patients requiring more than one course of induction to attain remission. Methods: This Acute Leukaemia Working Party study from the European Society for Blood and Marrow Transplantation identified adults who received an allograft in first CR from either a fully matched sibling or 10/10 or 9/10 human leucocyte antigen (HLA)‐matched unrelated donor (HLA‐A, HLA‐B, HLA‐C, HLA‐DR, or HLA‐DQ). Univariate and multivariate analyses were undertaken to identify the prognostic impact of one or two courses of induction to attain CR. Results: A total of 4995 patients were included with 3839 (77%) patients attaining a CR following one course of induction chemotherapy (IND1), and 1116 patients requiring two courses (IND2) to attain CR. IND2 as compared to IND1 was a poor prognostic factor in a univariate analysis and remained so in a multivariate Cox model, resulting in an increased hazard ratio of relapse (1.38; 95% confidence interval [CI], 1.16–1.64; p =.0003) and of death (1.27; 95% CI, 1.09–1.47; p =.002). Adverse prognostic factors in a multivariate analysis of the outcomes of patients requiring IND2 included age, FLT3‐ITD, adverse cytogenetics, and performance status. Pretransplant measurable residual disease retained a prognostic impact regardless of IND1 or IND2. Conclusion: Initial response to chemotherapy as determined by number of courses to attain CR, retained prognostic relevance even following SCT in CR. Patients requiring two courses of induction to attain complete remission (CR) have a higher incidence of relapse and inferior survival as compared to those who require one course. Pretransplant measurable residual disease remains important in predicting outcomes following an allogeneic stem cell transplant in those requiring two courses of induction to achieve CR. [ABSTRACT FROM AUTHOR]

Summary: Eculizumab is the first and only medication approved for paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS) treatment. However, eculizumab safety based on long‐term pharmacovigilance is unknown. This analysis summarises safety data collected from spontaneous and solicited sources from 16 March 2007 through 1 October 2016. Cumulative exposure to eculizumab was 28 518 patient‐years (PY) (PNH, 21 016 PY; aHUS, 7502 PY). Seventy‐six cases of meningococcal infection were reported (0·25/100 PY), including eight fatal PNH cases (0·03/100 PY). Susceptibility to meningococcal infections remained the key risk in patients receiving eculizumab. The meningococcal infection rate decreased over time; related mortality remained steady. The most commonly reported serious nonmeningococcal infections were pneumonia (11·8%); bacteraemia, sepsis and septic shock (11·1%); urinary tract infection (4·1%); staphylococcal infection (2·6%); and viral infection (2·5%). There were 434 reported cases of eculizumab exposure in pregnant women; of 260 cases with known outcomes, 70% resulted in live births. Reporting rates for solid tumours (≈0·6/100 PY) and haematological malignancies (≈0·74/100 PY) remained stable over time. No new safety signals affecting the eculizumab benefit‐risk profile were identified. Continued awareness and implementation of risk mitigation protocols are essential to minimise risk of meningococcal and other Neisseria infections in patients receiving eculizumab. [ABSTRACT FROM AUTHOR]

Summary: The incidence of acquired aplastic anaemia (AA) peaks in adolescents and young adults (AYA). Although age has been associated with response after immunosuppressive therapy (IST), few data exist about the specific outcome of AYA. We retrospectively compared the outcome of 29 children (aged <15 years), 32 AYA (15–25 years) and 23 adults (>25 years) with AA treated front‐line with IST in Saint‐Louis Hospital. The cumulative incidence of response was lower in adults compared with AYA (subdistribution hazard ratio [SHR] = 0·38, 95% confidence interval [CI] [0·96–1·00], P = 0·008), but no difference was observed between children and AYA (SHR = 0·84, 95% CI [0·96–1·00], P = 0·56), with a 6 months cumulative incidence of partial response of 44·8% in children, 62·5% in AYA and 21·7% in adults. The 5‐year failure‐free survival was 48·4%, without impact of age, with a 5‐year relapse rate of 20·7%. With a median follow‐up of 5·4 years, the 5‐year overall survival was 86·5%, without significant difference between children and AYA overall survival (hazard ratio [HR] 1·51, 95% CI [0·25–9·02], P = 0·66), while adults displayed poorer survival than AYA (HR 4·98, 95% CI [1·00–24·73], P = 0·049). This study confirms that age is a prognostic factor in AA patients treated with IST. However, AYA patients have a similar outcome to children in terms of response rate and survival. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Relapse and graft‐vs‐host disease (GVHD) are still the main complications after allogeneic hematopoietic stem cell transplantation, especially in the setting of reduced intensity regimen (RIC) and unrelated donor. We compared here anti‐thymocyte globulin (ATG) or alemtuzumab as GVHD prophylaxis in patients with myeloid disease transplanted after RIC and from an unrelated donor. Method: ATG and alemtuzumab patients have been matched by age, gender, HLA matching, comorbidities and cytogenetics risk (119 patients in each group). Results: After matching, we found that ATG decreased the risk of relapse (HR: 0.55, P = .0049) and improved relapse‐free survival (RFS, HR: 0.70, P = .042). The improved RFS with ATG was more pronounced in CMV‐positive patients but was not influenced by disease risk. Regarding overall survival, GVHD‐free relapse‐free survival and transplant‐related mortality, the risk was similar using ATG or alemtuzumab. Conclusion: Even if GVHD risk is lowered by alemtuzumab use, it does not translate in better outcome due to higher risk of relapse. [ABSTRACT FROM AUTHOR]

Background: Mobilized peripheral blood stem cells are currently the predominant source of grafts for allogeneic transplantation (allogeneic peripheral blood stem cell transplantation [allo-PBSCT]), although, in comparison with bone marrow, their use is associated with an increased risk of chronic graft-versus-host disease (cGVHD). Attempts to reduce the incidence of cGVHD include the addition of anti-thymocyte globulin (ATG) to the pretransplant conditioning regimen.Methods: The goal of this retrospective study was to analyze the effect of ATG on allo-PBSCT outcomes for adults with Philadelphia-negative acute lymphoblastic leukemia (Ph-neg ALL). The primary endpoint was survival free from relapse, grade 3 to 4 acute graft-versus-host disease (aGVHD), and cGVHD (ie, graft-versus-host disease-free/relapse-free survival [GRFS]). Nine-hundred twenty-four patients who underwent unmanipulated allo-PBSCT in their first complete remission between 2007 and 2016 were included. ATG was used in 97 of the 494 transplants from matched sibling donors (20%) and in 307 of the 430 transplants from human leukocyte antigen-matched (8 of 8 loci) unrelated donors (71%).Results: The use of ATG was an independent factor for an improved chance of GRFS (hazard ratio [HR], 0.70; P = .0009). Furthermore, it was associated with a reduced risk of both grade 2 to 4 (HR, 0.66; P = .005) and grade 3 to 4 aGVHD (HR, 0.58; P = .03). Similarly, its addition reduced the incidence of both total (HR, 0.45; P < 10-5 ) and extensive cGVHD (HR, 0.30; P < 10-5 ) as well as nonrelapse mortality (HR, 0.58; P = .01). No significant effect was found with respect to leukemia-free or overall survival. However, an increased risk of relapse was noted for those who received ATG (HR, 1.40; P = .04).Conclusions: Patients with Ph-neg ALL treated with allo-PBSCT benefit from the use of ATG in terms of improved GRFS. Its use may, therefore, be considered in this setting. Cancer 2018;124:2523-33. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 44-year-old man with asymptomatic Binet stage A chronic lymphocytic leukaemia (CLL). It mentions administration of courses of fludarabine, cyclophosphamide, alemtuzumab and high-dose methylprednisolone because of insufficient response and immune thrombocytopenia. It also mentions ibrutinib have the ability to enhance the activity of donor T cells in the context of relapse after haematopoietic stem cell transplantation (HSCT).

Paroxysmal nocturnal haemoglobinuria ( PNH) is characterized by chronic, uncontrolled complement activation resulting in elevated intravascular haemolysis and morbidities, including fatigue, dyspnoea, abdominal pain, pulmonary hypertension, thrombotic events ( TEs) and chronic kidney disease ( CKD). The long-term safety and efficacy of eculizumab, a humanized monoclonal antibody that inhibits terminal complement activation, was investigated in 195 patients over 66 months. Four patient deaths were reported, all unrelated to treatment, resulting in a 3-year survival estimate of 97·6%. All patients showed a reduction in lactate dehydrogenase levels, which was sustained over the course of treatment (median reduction of 86·9% at 36 months), reflecting inhibition of chronic haemolysis. TEs decreased by 81·8%, with 96·4% of patients remaining free of TEs. Patients also showed a time-dependent improvement in renal function: 93·1% of patients exhibited improvement or stabilization in CKD score at 36 months. Transfusion independence increased by 90·0% from baseline, with the number of red blood cell units transfused decreasing by 54·7%. Eculizumab was well tolerated, with no evidence of cumulative toxicity and a decreasing occurrence of adverse events over time. Eculizumab has a substantial impact on the symptoms and complications of PNH and results a significant improvement in patient survival. [ABSTRACT FROM AUTHOR]

Background: Relapse and transplant-related complications are leading causes of mortality after hematopoietic stem cell transplantation (HSCT). Suicides and accidents have not been studied in these patients. This study sought to determine whether there is an excess of suicide and accidental deaths after HSCT, and to determine risk factors.Methods: The incidence of suicidal and accidental death in patients after undergoing HSCT, standardized mortality ratio (SMR), and absolute excess risk (AER) of suicide and accidental deaths was determined, compared with the general European population. A case-control analysis was done to define factors associated with suicide and accidental deaths. Data were derived from the European Group for Blood and Marrow Transplantation Registry, including 294,922 patients who underwent autologous or allogeneic HSCT from 1980 to 2009.Results: The 10-year cumulative incidence of suicide and accidental deaths was 101.8 and 55.6 per 100,000 patients, respectively. SMR and AER of suicide after HSCT were 2.12 (P < .001) and 10.91, higher than in the European general population for 100,000 deaths, respectively. SMR and AER of accidental death were 1.23 (P < .05) and 2.54, respectively. In the case-control study, relapses were more frequent among patients who committed suicide after autologous HSCT (37% versus 18%; P < .0001). Chronic graft-versus-host disease was higher among patients who committed suicide after allogeneic HSCT (64% versus 37%; P = .001).Conclusions: There is an excess of deaths due to suicide and accidents in patients after undergoing HSCT as compared with the European general population. Relapse was associated with more suicide and accidental deaths after autologous HSCT, and chronic graft-versus-host disease was associated with more deaths by suicide after allogeneic HSCT. [ABSTRACT FROM AUTHOR]

BACKGROUND Relapse and transplant-related complications are leading causes of mortality after hematopoietic stem cell transplantation (HSCT). Suicides and accidents have not been studied in these patients. This study sought to determine whether there is an excess of suicide and accidental deaths after HSCT, and to determine risk factors. METHODS The incidence of suicidal and accidental death in patients after undergoing HSCT, standardized mortality ratio (SMR), and absolute excess risk (AER) of suicide and accidental deaths was determined, compared with the general European population. A case-control analysis was done to define factors associated with suicide and accidental deaths. Data were derived from the European Group for Blood and Marrow Transplantation Registry, including 294,922 patients who underwent autologous or allogeneic HSCT from 1980 to 2009. RESULTS The 10-year cumulative incidence of suicide and accidental deaths was 101.8 and 55.6 per 100,000 patients, respectively. SMR and AER of suicide after HSCT were 2.12 ( P < .001) and 10.91, higher than in the European general population for 100,000 deaths, respectively. SMR and AER of accidental death were 1.23 ( P < .05) and 2.54, respectively. In the case-control study, relapses were more frequent among patients who committed suicide after autologous HSCT (37% versus 18%; P < .0001). Chronic graft-versus-host disease was higher among patients who committed suicide after allogeneic HSCT (64% versus 37%; P = .001). CONCLUSIONS There is an excess of deaths due to suicide and accidents in patients after undergoing HSCT as compared with the European general population. Relapse was associated with more suicide and accidental deaths after autologous HSCT, and chronic graft-versus-host disease was associated with more deaths by suicide after allogeneic HSCT. Cancer 2013;119:2012-2021. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objectives and methods Chronic myelomonocytic leukemia ( CMML) is a severe disease for which allogeneic stem cell transplantation (allo- SCT) remains the only potentially curative treatment. We describe a retrospective study determining prognostic factors for outcome after allo- SCT in consecutive 73 patients with CMML reported to the SFGM- TC registry between 1992 and 2009. Results At diagnosis, median age was 53 yrs, and 36% patients had palpable splenomegaly (SPM). 48, 13, and 9 patients had good, intermediate, and poor risk karyotype, respectively, according to IPSS, 61% patients had CMML-1, and 39% had CMML-2. 41/31/1 cases had an HLA-identical sibling, an unrelated and haploidentical donor, respectively. 43 patients received reduced-intensity conditioning. With a median follow-up of 23 month, acute grade 2-4 and chronic GVHD developed in 21 and 25 patients, respectively. The 3-year OS, NRM (non-relapse mortality), EFS, and CIR (cumulative incidence of relapse) were 32%, 36%, 29% and 35%, respectively. OS was not influenced by the CR status, marrow blasts% at allo-SCT, prior treatments, and cGVHD. Using multivariate analysis, year of transplant < 2004 ( YOT) ( P = 0.005) was associated with higher NRM, YOT < 2004 ( P = 0.04) and SPM at allo- SCT ( P = 0.02) with lower EFS, and YOT < 2004 ( P = 0.03) and SPM at allo- SCT ( P = 0.04) with poorer OS. Conclusions Allogeneic stem cell transplantation is a valid treatment option for patients with CMML, and its outcome has improved with YOT > 2004. Splenomegaly seems to be a negative factor of OS and EFS in this series. [ABSTRACT FROM AUTHOR]

Allogeneic haematopoietic stem-cell transplantation (HSCT) is the only curative treatment for myelofibrosis. We report an analysis of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) registry including patients with myelofibrosis transplanted between 1997 and 2008. Potential risk factors affecting engraftment, non-relapse mortality (NRM), overall survival (OS) and progression-free survival (PFS) were analysed. One hundred and forty-seven patients, aged 20-68 (median 53) years, diagnosed with primary (53%) or secondary myelofibrosis underwent HSCT; 59% of patients were transplanted from a matched sibling donor. The conditioning regimen was myeloablative in 31% of patients. Ninety percent of the patients engrafted. Factors affecting favourably engraftment were splenectomy before HSCT, human leucocyte antigen (HLA) matched sibling donor, peripheral stem cell use as source of stem cells and absence of pre-transplant thrombocytopenia. Four-year OS, PFS and NRM survival were 39% (95%confidence interval [CI]: 31-50), 32% (95%CI: 24-43) and 39% (95%CI 30-48), respectively. Multivariate analysis indicated that HLA-identical sibling donor, chronic phase disease and splenectomy in men had favourable impact on OS. [ABSTRACT FROM AUTHOR]

The article offers information on the use of splenectomy in patients suffering from myelofibrosis (MF) after undergoing allogeneic haematopoietic stem cell transplantation (HSCT). It mentions that HSCT is considered to be the only curative treatment for MF patients as there is no clear recommendation for splenectomy and in some case it has led to either a higher or a reduced risk of relapse. It further presents case studies of 2 patients suffering from MF and underwent HSCT.

Haematopoietic stem cell transplantation (HCT) is the treatment of choice for defined malignant and non-malignant haematological disorders. The main drawbacks of HCT are early transplant-related mortality and late complications, which interfere with patient outcome, health status and quality of life. In comparison with other post-transplant complications, cardiac or cardiovascular consequences seem to occur at a much lower frequency. Early complications are usually associated with patient history before transplantation, primary diagnosis, age of the patient and associated comorbidities, and the type of transplantation and conditioning used. Late cardiac and cardiovascular events may occur years and even decades after HCT, and are related to cardiotoxic chemotherapy, mediastinal radiation therapy, gender, age at transplantation, cardiovascular risk factors and graft-versus-host disease in allogeneic HCT. As has been observed in long-term survivors of Hodgkin lymphoma, where the incidence of cardiovascular complications emerged as a significant problem with increasing follow-up, it is anticipated that the incidence of these complications after HCT will also increase significantly with increasing follow-up of the survivors. This review presents the available data on early and late cardiac and cardiovascular consequences after HCT, and presents recommendations for cardiac assessment and management of these complications. [ABSTRACT FROM AUTHOR]

Graft failure (GF) can be a fatal complication following haematopoietic stem cell transplantation (HSCT). We report four patients who developed early GF after unrelated HSCT and who subsequently received a double unrelated cord blood transplant (dUCBT) after reduced-intensity conditioning, at a median 15 d after the decision to perform a second transplant. Neutrophil recovery was observed in all four patients between day +15 and +31 with full donor chimaerism of one unit. Acute GVHD grades II–IV was observed in three patients. Three are alive, between 12 and 25 months after dUCBT. In conclusion, dUCBT is a promising procedure to treat early GF. [ABSTRACT FROM AUTHOR]

Summary. Allogeneic transplantation is the only curative treatment for Fanconi anaemia (FA) patients who develop myeloid malignancies. Dose-intensive preparative regimens, to decrease disease recurrence, lead to unacceptable transplant-related toxicity in FA. We report the outcome of three FA patients with such malignancies who underwent transplantation with reduced-intensity preparative regimens. This approach was well tolerated, even as second transplantations, and resulted in complete leukaemic remissions. However, the graft-versus-leukaemia effect was associated with fatal graft-versus-host disease. Even after transplantation, myeloid malignancies remain associated with a poor outcome in FA, and this argues in favour of early intervention when suitable donors are available. [ABSTRACT FROM AUTHOR]

Eosinophil-derived neurotoxin (EDN) is one of the four basic proteins stored in specific eosinophil granules. Here we demonstrate that EDN can also be detected at the surface of granulocytes. Reduction of EDN membrane expression after phosphatidylinositol-specific phospholipase C treatment suggests that a glycosylphosphatidylinositol (GPI) anchor is involved in the membrane association of EDN. The presence of a GPI anchor was confirmed by a lower expression of membrane EDN on granulocytes from patients with paroxysmal nocturnal hemoglobinuria which present cells lacking GPI anchor proteins. Furthermore, metabolic labeling with GPI anchor components supports biochemical evidence of GPI anchoring of EDN. [Copyright &y& Elsevier]

To evaluate the long-term immune reconstitution after allogeneic haematopoietic stem cell transplantation (SCT), we prospectively screened standard immune parameters in a series of 105 patients, at a median time of 15 months after SCT. Analysing lymphoid phenotypes, in vitro immune functions and immunoglobulin levels, we found that, more than 1 year post SCT, cellular and humoral immunity was still altered in a significant number of patients. CD4+ T cells were < 200/µl in one third of patients, and the CD4/CD8 ratio was still reversed in 78% of patients. Almost all patients showed positive T-cell responses against mitogens, but antigen-specific proliferation assays identified 20% to 80% of non-responders. B-cell counts were reconstituted in 61% of the patients, but levels of total immunoglobulins were still low in 59%. In multivariate analyses, human leucocyte antigen (HLA) disparity between donor and recipient and chronic graft-versus-host disease were the leading causes affecting immune reconstitution. Interestingly, cytomegalovirus (CMV) infections were strongly associated with normal CD8+ T-cell counts. Studying the impact of impaired immune reconstitution on the rate of infections occurring in the 6 years following screening, we identified three parameters (low B-cell count, inverted CD4/CD8 ratio, and negative response to tetanus toxin) as significant risk factors for developing such late infections. [ABSTRACT FROM AUTHOR]

Increasing numbers of patients are surviving after allogeneic haematopoietic stem cell transplantation (SCT). Among these patients, a number of late complications have been described but few data on the risk factors of these long-term effects of SCT are available. We report the analysis on 105 adult patients, surviving free of haematological disease at a median time of 15 months after SCT. At the time of screening, 52% had returned to work, general health status was normal in 67% and 47% were sexually active. Female patient gender odds ratio (OR) 2·9 (P = 0·01) and age > 25 years (OR = 3·2, P = 0·02) were associated with non-return to work. Decreased general status was associated with chronic graft-versus-host disease (GvHD) (OR = 3·2, P = 0·009) and irradiation (OR = 3·6, P = 0·004). Sexual inactivity was associated with younger age (OR = 7·0, P = 0·0002) and chronic GvHD (OR = 3·3, P = 0·006). Risk factors for altered pulmonary function tests included previous smoking habits, irradiation and chronic GvHD. Obstructive lung disease was associated with a previous history of asthma. Sicca syndrome and conjunctivitis were increased in patients with previous acute GvHD and cataracts were less frequent in patients with aplastic anaemia. Persistent impaired hair re-growth was less frequent in patients who received irradiation (OR = 0·18, P = 0·002) but increased in patients with previous acute GvHD (OR = 5·3, P = 0·007). Microalbuminuria was more frequent in irradiated patients (OR = 9·4, P = 0·05). Raised cholesterol was associated with age (OR = 20·8, P < 0·001), previous acute GvHD (OR = 4·7, P = 0·03), steroid use (OR = 6·3, P = 0·001) and familial hypercholesterolaemia (OR = 4·4, P = 0·04). Decreased bone density was associated with chronic GvHD (OR = 3·9, P = 0·001). Thus, using routine tests in adult patients we were able to detect significant numbers of-non-symptomatic complications enabling early treatment. [ABSTRACT FROM AUTHOR]

In this retrospective multicentre study, we analysed the results of 82 consecutive second early allogeneic transplants for primary (n = 28) or secondary (n = 54) graft failures performed between 1985 and 1997 in patients with acute leukaemia (n = 33), aplastic anaemia (n = 29) or chronic myeloid leukaemia (n = 20). HLA-matched siblings were used in 64 cases. The same donors were used for both transplants in 56 cases and the first transplant was T-cell depleted in 30 cases. The median age at transplant was 25 years and the median intertransplant time interval was 2 months. Estimates of the 3-year overall survival and day 100 transplant-related mortality were 30% and 53% respectively. A recipient age < 34 years at transplant, an intertransplant time interval ≥ 80 d and a positive recipient cytomegalovirus serology were predictors of a better outcome. The use of cyclosporin A (CsA) after second transplant had a dramatic impact on outcome, the best results being observed with CsA alone. The day 40 probability of neutrophil recovery was 73%. The use of peripheral blood progenitor cells (PBPCs) was associated with a higher and faster neutrophil recovery. Other factors associated with neutrophil recovery were an intertransplant time interval ≥ 80 d and a positive recipient cytomegalovirus serology. Therefore, second early allogeneic transplantation for graft failure is an effective treatment, especially if patients can receive CsA for graft-versus-host disease prevention and are retransplanted more than 80 d from first transplant. [ABSTRACT FROM AUTHOR]

We describe the long-term follow-up of 50 Fanconi's anaemia patients who were transplanted from a related donor with a median follow-up of >6 years. The survival estimate was 74.4% at 54 months and 58.5% at 100 months. All patients were conditioned with low-dose cyclophosphamide and thoraco-abdominal irradiation. Acute graft-versus-host disease (GvHD) of grade II or more developed in 26 patients and chronic GvHD developed in 30/43 (69.9%) patients. The survival of patients without chronic GvHD (n = 13) was 100%. In addition to chronic GvHD, 20 pre-transplant transfusions was shown to have an adverse impact on survival by multivariate analysis (relative risk = 7.08, P = 0.0003). Prospective follow-up of growth and endocrine function could be performed in 31 patients. Of 20 boys, six have already reached normal puberty within the expected time. Among the 11 girls, three were at the pubertal age at the time of analysis. Growth retardation was common, whereas late complications (e.g. peripheral hypothyroidism, cataract) were rare. However, the most important long-term complication was the occurrence of cancer in seven patients (8-year projected incidence 24%). Among the 32 survivors, 27 (84.5%) had a normal and four a moderately reduced performance status, and all achieved complete engraftment with donor cells. Therefore transplantation was able to cure these patients who remain at high risk for developing late complications. Clearly, a genetic predisposition and chronic GvHD could have led to the development of these cancers. However, we cannot completely rule out irradiation as a cofactor in the genesis of these cancers, and therefore no longer use irradiation for the conditioning of Fanconi's anaemia patients. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the possible role of PIGA mutations for paroxysmal nocturnal haemoglobinuria (PNH) in inducing endothelial dysfunction and in affecting a common endothelial and haematopoietic progenitor cell. The endothelial colony-forming cells (ECFC) obtained from peripheral blood of a sample of patients with PNH were tested as surrogate of endothelial cell genetic status. It has found that PIGA mutations are not present in ECFC from patients with PNH.

The article presents a study on the antiphospholipid antibodies (APA) in patients with paroxysmal nocturnal haemoglobinuria (PNH). The study observed twenty PNH patients enrolled in French centres and were given an eculizumab by intravenous infusion. Results showed that thirteen patients had at least two lupus anticoagulants (LA) assays and APA presence was still detected after eleven weeks, leading to the non-relation of eculizumab to APA level reduction.

The article presents the clinical and biological characteristics of five patients diagnosed with aplastic anaemia (AA) and coeliac disease (CD) at a medical center. Two patients were diagnosed with CD before AA while in other three patients CD was diagnosed at the same time as AA. Severity of AA was graded in patients from nonsevere to very severe AA. All patients had normal bone marrow cytogenetics and two had paroxysmal nocturnal haemoglobinuria (PNH).

A letter to the editor is presented in response to the article that show evidence of Th1, Th17 and Tc17 cells in psoriasiform chronic graft-versus-host disease.

The article presents a case study of a 61-year-old man who was diagnosed with multiple myeloma in 2009. It describes the patient's condition who developed transplantation-associated thrombotic microangiopathy (TA-TMA) following allogeneic haematopoietic stem cell transplantation (HSCT). It notes that the patient's increased dosage of steroids to treat his graft-versus-host disease (GvHD) of the skin and gut two months after HSCT has led to TA-TMA.

Data on haematological features of telomere biology disorders (TBD) remain scarce. We describe haematological, extra-haematological characteristics and prognosis of 127 genetically confirmed TBD patients diagnosed after the age of 15. Ninety-three index cases and 34 affected relatives were included. At diagnosis of TBD, 76.3% of index cases had haematological features, half pulmonary features and a third liver features. At diagnosis, bone marrow failure (BMF) was present in 59 (46.5%), myelodysplastic syndrome (MDS) in 22 (17.3%) and acute myeloid leukaemia (AML) in 2 (1.6%) while 13 (10.2%) developed or worsened bone marrow involvement during follow-up. At diagnosis, compared to MDS/AML patients, BMF patients were younger (median 23.1 years vs. 43.8, p = 0.007), and had a better outcome (4-year overall survival 76.3% vs. 31.8%, p < 0.001). While frequencies and burden of cytogenetical and somatic mutations increased significantly in myeloid malignancies, some abnormalities were also observed in patients with normal blood counts and BMF, notably somatic spliceosome variants. Solid cancers developed in 8.7% patients, mainly human papillomavirus-related cancers and hepatocellular carcinomas. TBD is a multiorgan progressive disease. While BMF is the main haematological disorder, high-risk myeloid malignancies are common, and are, together with age, the only factors associated with a worse outcome., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Matching for HLA-A, -B, -C, and -DRB1 loci (8/8 match) is currently the gold standard for unrelated donor hematopoietic cell transplantation (HCT). In Europe, patients are also matched at the HLA-DQB1 loci (10/10 match). However, there is increasing evidence that matching at HLA-DRB3/4/5 loci may help to lower transplant-related morbidity and mortality. We therefore investigated the impact of HLA-DRB3/4/5 mismatches on outcomes in 1975 patients who received a first 10/10 matched unrelated donor (MUD) HCT in France from 2000 to 2012 for a hematological malignancy. High-resolution typing was performed at HLA-A, -B, -C, -DRB1, -DQB1, -DPB1, and -DRB3/4/5 loci for all donor/recipient pairs. Compared with DRB3/4/5-matched pairs, patients who received a MUD HCT from a DRB3/4/5 mismatched donor had a significantly increased risk of grade II-IV acute graft-versus-host disease (aGVHD) (Adjusted Hazard Ratio (HR) 1.43 (1.07 to 1.90)) associated with lower graft-versus-host disease-free and relapse-free survival (GRFS) (Adjusted HR 1.20 (1.02 to 1.42)). Conversely, we observed no differences in terms of chronic GVHD, nonrelapse mortality, relapse and overall survival. However, we believe that patients stand to benefit from DRB3/4/5 loci being considered for unrelated donor selection to improve GRFS and then quality of life after unrelated HCT., (© 2018 Wiley Periodicals, Inc.)

The potential role of the infused B cell subset after Hematopoietic Stem Cell Transplantation has not been yet studied. The present study analyzed the impact of B cells on transplant outcome in 254 patients who received a bone marrow graft from a human leucocyte antigen-identical sibling donor. The influence of B lineage-specific hematopoietic progenitor cells (CD34(+) CD19(+)) and B cells (immature and mature B cells, CD34(-) CD19(+)) was also analyzed. All included patients received a myeloablative regimen. The cumulative incidence function of acute graft-versus-host (GvHD) grade II to IV was 48% and was inversely associated with the number of CD34(+) CD19(+). There were no statistically significant associations between B cell subsets and chronic GvHD or survival. The CD34(+) CD19(+) B cell subset remained significantly associated with acute GvHD in multivariate analysis (Relative risk = 0.32, 95% confidence interval: 0.11-0.92, P = 0.035). In conclusion, a higher B lineage-specific hematopoietic progenitor cells (CD34(+) CD19(+)) cell dose is associated with a significant decrease incidence of acute GvHD.

Ninety-one patients were studied serially for chimeric status following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA) or Fanconi Anaemia (FA). Short tandem repeat polymerase chain reaction (STR-PCR) was used to stratify patients into five groups: (A) complete donor chimeras (n = 39), (B) transient mixed chimeras (n = 15) (C) stable mixed chimeras (n = 18), (D) progressive mixed chimeras (n = 14) (E) recipient chimeras with early graft rejection (n = 5). As serial sampling was not possible in Group E, serial chimerism results for 86 patients were available for analysis. The following factors were analysed for association with chimeric status: age, sex match, donor type, aetiology of aplasia, source of stem cells, number of cells engrafted, conditioning regimen, graft-versus-host disease (GvHD) prophylaxis, occurrence of acute and chronic GvHD and survival. Progressive mixed chimeras (PMCs) were at high risk of late graft rejection (n = 10, P < 0.0001). Seven of these patients lost their graft during withdrawal of immunosuppressive therapy. STR-PCR indicated an inverse correlation between detection of recipient cells post-SCT and occurrence of acute GvHD (P = 0.008). PMC was a bad prognostic indicator of survival (P = 0.003). Monitoring of chimeric status during cyclosporin withdrawal may facilitate therapeutic intervention to prevent late graft rejection in patients transplanted for SAA.

In paroxysmal nocturnal haemoglobinuria (PNH), chronic destruction of PNH red blood cells (RBCs) by complement leads to anaemia and other serious morbidities. Eculizumab inhibits terminal complement-mediated PNH RBC destruction by targeting C5. In the phase III, double-blind, placebo-controlled, TRIUMPH study, eculizumab reduced haemolysis, stabilized haemoglobin levels, reduced transfusion requirements and improved fatigue in patients with PNH. Herein, we explored the effects of eculizumab on measures of anaemia in patients from the TRIUMPH study and the open-label SHEPHERD study, a more heterogeneous population. Eculizumab reduced haemolysis regardless of pretreatment transfusion requirements and regardless of whether or not patients became transfusion-dependent during treatment (P < 0.001). Reduction in haemolysis was associated with increased PNH RBC counts (P < 0.001) while reticulocyte counts remained elevated. Eculizumab-treated patients demonstrated significantly higher levels of haemoglobin as compared with placebo in TRIUMPH and relative to baseline levels in SHEPHERD (P < 0.001 for each study). Eculizumab lowered transfusion requirement across multiple pretreatment transfusion strata and eliminated transfusion support in a majority of both TRIUMPH and SHEPHERD patients (P < 0.001). Patients who required some transfusion support during treatment with eculizumab showed a reduction in haemolysis and transfusion requirements and an improvement in fatigue. Eculizumab reduces haemolysis and improves anaemia and fatigue, regardless of transfusion requirements.