Actinomycosis after allogeneic hematopoietic stem cell transplantation despite penicillin prophylaxis.

Actinomycosis is a rare chronic and multifaceted disease caused by Actinomyces species frequently mimicking malignancy or other chronic granulomatous lung diseases. We report 4 original presentations of actinomycosis arising under supposed penicillin prophylaxis in allogeneic stem cell transplantation recipients.

Cerebrovascular events as presenting manifestations of Myeloproliferative Neoplasm.

AIM: To determine the incidence and main characteristics of cerebrovascular events as the presenting manifestations of myeloproliferative neoplasm (MPN). METHODS: The Hematology in Lyon (HEMILY) registry is a prospective database (763 patients) of all cases of MPN diagnosed since 2005 in the Rhône-Alpes district of France. The MPN cases were divided into four groups: polycythemia vera (PV); essential thrombocythemia (ET); myelofibrosis (MF); and atypical MPN. The ischemic stroke subtype was classified according to TOAST criteria. RESULTS: A stroke history revealed MPN in 35 (4.3%) patients: 22 (63%) had an ischemic stroke; eight (23%) had a transient ischemic attack; four (11%) had cerebral venous thrombosis; and one (3%) had hemorrhagic stroke. All patients had hemoglobin and/or platelet count abnormalities. In addition, 12 (34%) patients had PV, 21 (60%) had ET, one (3%) had MF and one (3%) had atypical/unclassified MPN. The JAK2 V617F mutation was found in 83% of patients. In 18 (51%) patients, an additional mechanism of stroke was present (atherosclerosis in 10 patients, atrial fibrillation in one patient and dissection in another). The median NIHSS score at entry was 2, and the median modified Rankin Scale score at 3 months was 0. Compared with the general MPN population, stroke-MPN patients presented with significantly higher levels of hemoglobin (P<0.001) and were more frequently positive for the JAK2 V617F mutation (P=0.044). CONCLUSION: Stroke revealing MPN is rare. However, careful attention should still be paid to blood counts even in patients with obvious stroke etiologies, as early diagnosis permits prompt treatment and decreases the risk of recurrence, thus limiting morbidity and mortality.

Invasive aspergillosis: an important risk factor on the short- and long-term survival of acute myeloid leukemia (AML) patients.

Invasive aspergillosis (IA) during induction chemotherapy of acute myeloid leukemia (AML) could worsen the prognosis. Our objective was to study how the development of IA during AML interferes with the therapeutic strategy and to evaluate its impact on the short- and long-term survival. Newly diagnosed AML patients between the years 2004 and 2007 were retrospectively analyzed. The outcome was death of the patient. A Cox proportional hazards model with the diagnosis of IA and post-induction response evaluation as the main exposure was fitted. Overall, 262 patients were analyzed and 58 IA were observed. The 2-year survival of patients having had remission of AML was 54% and, for patients with failure of chemotherapy, it was 5% (p < 0.001). The 2-year survival of patients having had IA was 14%, and without IA, it was 32% (p = 0.01). Multivariate analysis showed that IA was associated with a higher risk of death in case of remission compared to no IA (hazard ratio [HR] = 1.66 [1.05-2.65], p = 0.031) and also in case of failure (HR = 6.43, p < 0.001). IA was associated with an increased risk of death for patients if they were either in remission or in failure after induction chemotherapy.

Role of the pathologist in organ transplantation: the North Italy Transplant program experience.

The North Italy Transplant program (NITp) is one of the three organ exchange organizations in Italy together with AIRT and OCST, supervised by the Centro Nazionale Trapianti. It started its activity on June 18, 1972 and serves an area of about 18 million inhabitants in northern Italy. From June 18, 1972 to December 31, 2004, 5761 cadaveric donors have been used and 18,390 transplants performed in the NITp. At December 31, 2004, the NITp waiting list included 3407 patients (2261 kidney, 425 heart, 387 liver, 153 pancreas, 181 lung). From January 1 to August 31, 2005, 13 donors with cancer were used, namely, 4.2% of the overall number of procured donors. The yearly projection of this figure is more than twofold above that in the previous year. Pathologists play a crucial role in NITp activity, by assessing donor suitability and organ quality, by performing the autopsy control of donors, and by participating in transplant follow-up. In addition the pathologist responsible for the Veneto-centralized pathology unit plays the role of expert for second opinion for the NITp area. Pathologists are involved in expanding the pool of donors by analyzing organ biopsies in specific programs. Eight HBV(+) and/or HCV(+) liver biopsies have been evaluated during 2003 and 18 during 2004 and 12 livers, according to the protocol, were suitable for transplantation, and 14 double kidney transplantations were performed in 2003 and 35 in 2004.

A matched case-control study of toxoplasmosis after allogeneic haematopoietic stem cell transplantation: still a devastating complication.

Toxoplasmosis (TXP) is a life-threatening complication of allogeneic haematopoietic stem cell transplantation (AHSCT). Little is known about the risk factors and there is no consensus on prophylactic measures. To investigate the risk factors, we conducted a single-centre, retrospective matched case-control study among adults who underwent AHSCT from January 2006 to March 2015 in our hospital. TXP cases were identified from the prospectively maintained hospital's database. The 1:2 control population consisted of the two patients who received an AHSCT immediately before and after each case with similar donor relationship (related, unrelated) but who did not develop TXP. Risk factors were identified by conditional logistic regression. Clinical features and outcome of TXP were examined. Twenty-three (3.9%) cases of TXP (20 diseases, three infections) were identified among 588 AHSCT recipients. Twenty (87%) cases had a positive pre-transplant Toxoplasma gondii serology. In comparison with 46 matched control patients, risk factors were the absence of effective anti-Toxoplasma prophylaxis (odds ratio (OR) 11.95; 95% CI 3.04-46.88; p <0.001), high-grade (III-IV) acute graft-versus-host-disease (OR 3.1; 95% CI 1.04-9.23; p 0.042) and receipt of the tumour necrosis factor-α blocker etanercept (OR 12.02; 95% CI 1.33-108.6; p 0.027). Mortality attributable to TXP was 43.5% (n = 10). Non-relapse mortality rates during the study period of cases and controls were 69.6% (n = 16) and 17.4% (n = 8), respectively. Lung involvement was the dominant clinical feature (n = 14). Two cases were associated with graft failure, one preceded by haemophagocytic syndrome. Given TXP-related morbidity and attributable mortality, anti-Toxoplasma prophylaxis is essential for optimized management of seropositive AHSCT recipients.

[Renal transplantation in the North Italy Transplant program (NITp): Organ allocation and results]. / Il trapianto renale nel Nord Italia Transplant program (NITp): assegnazione degli organi e risultati.

Renal transplantation is an effective therapeutic tool for patients with end-stage renal diseases (ESRDs). Data reported in this article summarize the results obtained from 30 years' activity in the North Italy Transplant program (NITp), the first transplant organization in Italy that implemented a donor procurement and organ transplantation network. In the NITp kidney allocation is governed by a computerized algorithm, NITK3, put in place in 1997, aimed at ensuring equity, transparency and traceability during the stages of the allocation decision-making process. The NITp working group has recognized the NITK3 criteria and they are periodically reviewed following the results of the analysis of patients' transplantation odds. The results obtained with the use of the NITK3 algorithm have been very satisfactory: after 6 yrs, a significantly higher percentage of patients at immunological risk (sensitized or waiting for re-transplant), of patients waiting for >3 yrs and of patients with 0-1 HLA A,B,DR mismatches have been transplanted. Moreover, a higher percentage of kidneys were used locally (in a hospital within the procurement area), and this is known to stimulate donor procurement. Finally, we performed a preliminary statistical analysis of transplants carried out from 1998-2002 in 5/16 centers of the NITp area, demonstrating the quality of the NITp program in terms of patient and graft survival, and that donor and recipient age are the variables significantly impacting on transplant results.

Suggestive evidence of a role of HLA-DRB4 mismatches in the outcome of allogeneic hematopoietic stem cell transplantation with HLA-10/10-matched unrelated donors: a French-Swiss retrospective study.

We have conducted a retrospective study on 251 patients from three centers in France and Switzerland between 2004 and 2010 with the goal to evaluate the impact of HLA-DRB3/B4/B5 allele mismatching after HLA-10/10-matched unrelated allogeneic hematopoietic stem cell transplantation (HSCT). Fourteen (5.5%) patients receiving HSCT from an HLA-10/10-matched unrelated donor had a mismatched DRB4 donor, 23 (9.5%) patients had a mismatched DRB3 donor and 214 (85%) had a fully matched unrelated donor (HLA-10/10) without DRB3- or DRB4-mismatched donor. We compared the outcomes of 37 patients with a DRB3 or DRB4 mismatch with the rest of the population. The median survival for a patient without DRB3/4 mismatch was 18 months (95% confidence interval (CI), 13-29), for DRB3-mismatched patients 32 months (95% CI, 13-NR) and for DRB4-mismatched patients 7 months (95% CI, 3-NR). The multivariate analysis showed a significant impact of DRB4 mismatching on survival (Hazards ratio (HR)=2.1 (95% CI, 1.01-4.67), P=0.045), acute GvHD (HR=2.66 (95% CI, 0.99-7.09) P=0.05) and on transplant-related mortality (HR=2.8; (95% CI, 1.7-4.4) P=0.024). In the view of an impact of DRB4 locus mismatch on clinical outcome, it would be important to confirm this observation in a prospective study as it may be worth considering DRB4 in the unrelated donor selection.

Pre-transplantation risk factors to develop sclerotic chronic GvHD after allogeneic HSCT: a multicenter retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

Sclerotic chronic GvHD (cGvHD) is one of the most severe complications after allo-hematopoietic stem cell transplantation (HSCT). Risk factors associated with this complication remain not very well defined. With the aim to define a pre-transplantation risk profile, we have conducted a French retrospective analysis in 705 consecutive patients between 2005 and 2010. Analyses to determine pre-transplantation risk factors included as variables: patient and donor age, kind of donor, HLA matching, ABO matching, sex-matching, diagnosis, stem cell source, gender, GvHD prophylaxis and antithymocyte globulin (ATG) in the conditioning regimen. The cumulative incidence of sclerotic cGvHD was 18% (95% CI, 16.6-19.6) 3 years after onset of cGvHD. In univariate analysis, we found a significantly lower number of sclerotic cGvHD form in patients transplanted from cord blood cells (P=0.0021), in patients with a one mismatched donor (P=0.041) and in patients who had received ATG in the conditioning regimen (P=0.002). In multivariate analysis, factors associated with an increased risk of sclerotic cGvHD were young patient age, multiple myeloma and PBSC as the stem cell source. ATG in conditioning regimen and cord blood unit as the stem cell source were associated with a lower risk.

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation.

BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P=0.028), unrelated donor (P=0.0178), stem cell source (P=0.0001), HLA mismatching (P=0.0022) and BU in conditioning regimen (P=0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P=0.0005) and peripheral blood stem cells (P=0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P=0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (P<0.0001), more RBC (P=0.0003) and platelet transfusions (P<0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at \[euro]2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

A case of complete adenylate kinase deficiency due to a nonsense mutation in AK-1 gene (Arg 107 --> Stop, CGA --> TGA) associated with chronic haemolytic anaemia.

Two siblings of Italian origin with mild chronic haemolytic anaemia, psychomotor impairment and undetectable adenylate kinase (AK) activity are reported. The other red cell enzyme activities were normal except for a slight decrease of PFK. 2,3-DPG levels were increased in both siblings, and AMP decreased in one only. The parents were not consanguineous and displayed intermediate AK activity. The sequence of complete erythrocyte AK-1 cDNA showed the presence of a nonsense homozygous mutation at codon 107 (CGA --> TGA, Arg --> Stop) in the siblings. The mutation results in a truncated protein of 107 amino acids in comparison with the 194 of the normal one. Moreover a 37 bp deletion in the first part of exon 6 (from nt 326 to nt 362 of the cDNA sequence) was detected in one allele; this deletion is not likely to further affect the enzyme structure, being localized after the stop codon. The new variant was named AK Fidenza, from the origin of the patients.