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Among the three classic Philadelphia chromosome-negative myeloproliferative neoplasms, primary myelofibrosis (PMF) is the most severe in terms of disease biology, survival and quality of life. Abnormalities in the process of differentiation of PMF megakaryocytes (MKs) are a hallmark of the disease. Nevertheless, the molecular events that lead to aberrant megakaryocytopoiesis have yet to be clarified. Protein kinase Cɛ (PKCɛ) is a novel serine/threonine kinase that is overexpressed in a variety of cancers, promoting aggressive phenotype, invasiveness and drug resistance. Our previous findings on the role of PKCɛ in normal (erythroid and megakaryocytic commitment) and malignant (acute myeloid leukemia) hematopoiesis prompted us to investigate whether it could be involved in the pathogenesis of PMF MK-impaired differentiation. We demonstrate that PMF megakaryocytic cultures express higher levels of PKCɛ than healthy donors, which correlate with higher disease burden but not with JAK2V617F mutation. Inhibition of PKCɛ function (by a negative regulator of PKCɛ translocation) or translation (by target small hairpin RNA) leads to reduction in PMF cell growth, restoration of PMF MK differentiation and inhibition of PKCɛ-related anti-apoptotic signaling (Bcl-xL). Our data suggest that targeting PKCɛ directly affects the PMF neoplastic clone and represent a proof-of-concept for PKCɛ inhibition as a novel therapeutic strategy in PMF. [ABSTRACT FROM AUTHOR]

For patients with hematologic malignancies at high risk of relapse who do not have matched donors, a suitable alternative stem cell source is the HLA-haploidentical 2- or 3-loci mismatched family donor who is readily available for nearly all patients. Transplantation across the major HLA barrier is associated with strong T-cell alloreactions, which were originally manifested as a high incidence of severe GVHD and graft rejection. The present overview of the 7th symposium on haplidentical transplantation that took place at the Weizmann Institute on February 2014, shows how these obstacles to successful transplantation can now be overcome. The review also discusses the advantages and drawbacks of current options for full haplotype-mismatched transplantation and highlights innovative approaches for rebuilding immunity, reducing leukemia relapse and improving survival after transplantation. In addition, new modalities for immune tolerance induction following nonmyeloablative conditioning are discussed, showing new options for treatment of elderly patients who cannot tolerate myeloablative conditioning protocols, as well as novel strategies for immune tolerance and chimerism induction as a platform for cell therapy and organ transplantation. [ABSTRACT FROM AUTHOR]

We investigated the influence of molecular status on disease characteristics and clinical outcome in young patients (⩽40 years) with World Health Organization (WHO)-defined essential thrombocythemia (ET) or early/prefibrotic primary myelofibrosis (early-PMF). Overall, 217 patients with ET (number 197) and early-PMF (number 20) were included in the analysis. Median follow-up time was 10.2 years. The cumulative incidence of thrombosis, hemorrhages and disease evolution into myelofibrosis/acute leukemia were 16.6%, 8.6% and 3% at 15 years, respectively. No differences were detectable between ET and early-PMF patients, although the latter cohort showed a trend for worse combined-event free survival (EFS). Mutation frequency were 61% for JAK2V617F, 25% for CALR and 1% for MPLW515K, and were comparable across WHO diagnosis; however, JAK2V617F allele burden was higher in the early-PMF group. Compared with JAK2V617F-positive patients, CALR-mutated patients displayed higher platelet count and lower hemoglobin level. CALR mutations significantly correlated with lower thrombotic risk (9.1% versus 21.7%, P=0.04), longer survival (100% versus 96%, P=0.05) and better combined-EFS (86% versus 71%, P=0.02). However, non-type 1/type 2 CALR mutations ('minor' mutations) and abnormal karyotype were found to correlate with increased risk of disease evolution. At last contact, six patients had died; in five cases, the causes of death were related to the hematological disease and occurred at a median age of 64 years (range: 53-68 years). Twenty-eight patients (13%) were unmutated for JAK2, CALR and MPL: no event was registered in these 'triple-negative' patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning a study which examines the interleukin-3 (IL-3) bone remodeling effects' mediators in multiple myeloma (MM).

Study design:Prospective study.Objectives:The objective of this study was to assess the prevalence of small intestinal bacterial overgrowth (SIBO), methane (CH4) production and orocecal transit time (OCTT) in children affected by myelomeningocele.Setting:This study was conducted at the Catholic University in Rome, Italy.Methods:Eighteen (6M/12F; 16.4±7.6 years) children affected by myelomeningocele were enrolled. All subjects underwent H2/CH4 lactulose breath tests to assess SIBO and OCTT. All patients performed a visual analog scale to investigate abdominal pain, bloating and flatulence, and maintained a diary of the frequency and consistency of the stool during the previous 7 days. A nephro-urological clinical evaluation of the number of urinary tract infections (UTIs) and neurogenic bowel disease score were also performed.Results:Thirty-nine percent (7/18) of the children showed SIBO and 61% (11/18) presented a delayed OCTT. Moreover 44.4% (8/18) produced high levels of CH4. Interestingly, all myelomeningocele children who produced CH4 showed a delayed OCTT and a higher incidence of UTI, with a lower frequency of evacuation, compared with those with a normal or accelerated OCTT.Conclusion:The association between CH4 and constipation suggests that CH4 has an active role in the development of constipation. One of the most interesting features of our study is to identify a correlation between myelomeningocele, CH4, delayed OCTT and UTI. The intestinal decontamination with locally acting drugs in these children may reduce the number of UTIs and improve intestinal motility. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible transcription factor-1 (HIF-1α) is overexpressed in multiple myeloma (MM) cells within the hypoxic microenvironment. Herein, we explored the effect of persistent HIF-1α inhibition by a lentivirus short hairpin RNA pool on MM cell growth either in vitro or in vivo and on the transcriptional and pro-angiogenic profiles of MM cells. HIF-1α suppression did not have a significant impact on MM cell proliferation and survival in vitro although, increased the antiproliferative effect of lenalidomide. On the other hand, we found that HIF-1α inhibition in MM cells downregulates the pro-angiogenic genes VEGF, IL8, IL10, CCL2, CCL5 and MMP9. Pro-osteoclastogenic cytokines were also inhibited, such as IL-7 and CCL3/MIP-1α. The effect of HIF-1α inhibition was assessed in vivo in nonobese diabetic/severe combined immunodeficiency mice both in a subcutaneous and an intratibial MM model. HIF-1α inhibition caused a dramatic reduction in the weight and volume of the tumor burden in both mouse models. Moreover, a significant reduction of the number of vessels and vascular endothelial growth factors (VEGFs) immunostaining was observed. Finally, in the intratibial experiments, HIF-1α inhibition significantly blocked bone destruction. Overall, our data indicate that HIF-1α suppression in MM cells significantly blocks MM-induced angiogenesis and reduces MM tumor burden and bone destruction in vivo, supporting HIF-1α as a potential therapeutic target in MM. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible transcription factor-1 (HIF-1α) is overexpressed in multiple myeloma (MM) cells within the hypoxic microenvironment. Herein, we explored the effect of persistent HIF-1α inhibition by a lentivirus short hairpin RNA pool on MM cell growth either in vitro or in vivo and on the transcriptional and pro-angiogenic profiles of MM cells. HIF-1α suppression did not have a significant impact on MM cell proliferation and survival in vitro although, increased the antiproliferative effect of lenalidomide. On the other hand, we found that HIF-1α inhibition in MM cells downregulates the pro-angiogenic genes VEGF, IL8, IL10, CCL2, CCL5 and MMP9. Pro-osteoclastogenic cytokines were also inhibited, such as IL-7 and CCL3/MIP-1α. The effect of HIF-1α inhibition was assessed in vivo in nonobese diabetic/severe combined immunodeficiency mice both in a subcutaneous and an intratibial MM model. HIF-1α inhibition caused a dramatic reduction in the weight and volume of the tumor burden in both mouse models. Moreover, a significant reduction of the number of vessels and vascular endothelial growth factors (VEGFs) immunostaining was observed. Finally, in the intratibial experiments, HIF-1α inhibition significantly blocked bone destruction. Overall, our data indicate that HIF-1α suppression in MM cells significantly blocks MM-induced angiogenesis and reduces MM tumor burden and bone destruction in vivo, supporting HIF-1α as a potential therapeutic target in MM. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether parameters related to TBI impacted upon OS and relapse in patients with acute leukemia in CR who underwent haematopoietic SCT (HSCT) in 11 Italian Radiation Oncology Centres. Data were analysed from 507 patients (313 males; 194 females; median age 15 years; 318 with ALL; 188 with AML; 1 case not recorded). Besides 128 autologous transplants, donors included 192 matched siblings, 74 mismatched family members and 113 unrelated individuals. Autologous and allogeneic transplants were analysed separately. Median follow-up was 40.1 months. TBI schedules and HSCT type were closely related. Uni- and multi-variate analyses showed no parameter was significant for OS or relapse in autologous transplantation. Multivariate analysis showed type of transplant and disease impacted significantly on OS in allogeneic transplantation. Disease, GVHD and TBI dose were risk factors for relapse. This analysis illustrates that Italian Transplant Centre use of TBI is in line with international practice. Most Centres adopted a hyperfractionated schedule that is used worldwide (12 Gy in six fractions over 3 days), which appears to have become standard. TBI doses impacted significantly upon relapse rates. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is characterized by the impaired osteogenic differentiation of human mesenchymal stromal cells (hMSCs). Canonical Wnt signaling is critical for the regulation of bone formation, however, recent evidence suggests that the non-canonical Wnt agonist Wnt5a stimulates human osteoblastogenesis through its co-receptor Ror2. The effects of MM cells on non-canonical Wnt signaling and the effect of the activation of this pathway on MM-induced osteoblast exhaustion are not known and were investigated in this study. We found that the osteogenic differentiation of bone marrow hMSCs toward osteoprogenitor cells (PreOB) significantly increased Ror2 expression, and that MM cells inhibit Ror2 expression by PreOB in co-culture by inhibiting the non-canonical Wnt5a signaling. The activation of the non-canonical Wnt pathway in hMSCs by means of Wnt5a treatment and the overexpression of Wnt5 or Ror2 by lentiviral vectors increased the osteogenic differentiation of hMSCs and blunted the inhibitory effect of MM in co-culture. Consistently, Wnt5a inhibition by specific small interfering RNA reduced the hMSC expression of osteogenic markers. Our findings demonstrate that the Wnt5a/Ror2 pathway is involved in the pathophysiology of MM-induced bone disease and that the activation of the non-canonical Wnt5a/Ror2 pathway in hMSCs increases osteogenic differentiation and may counterbalance the inhibitory effect of MM cells. [ABSTRACT FROM AUTHOR]

In adults, one-haplotype-mismatched haematopoietic SCT (haploidentical HSCT) is associated with slow immune recovery due to decaying thymic function and extensive T-cell depletion of the graft. Although essential for preventing GVHD, T-cell depletion underlies the major reasons for transplant failure: leukemia relapse and infections, with infection-related mortality accounting for about 40% of non-leukemic deaths. Adoptive T-cell therapy would be helpful for these patients but to administer it without causing GVHD, alloreactive T cells need to be eliminated from donor T lymphocytes before infusion. In a preclinical study, to address this problem, we determined the efficacy of photodynamic purging of alloreactive T cells, by investigating combinations of parameters in order to achieve maximum allodepletion, preservation of T-regulatory cells and of pathogen and leukemia-specific T-cell responses in donor-vs-recipient MLR. We also needed to identify an optimal method to quantify the Ag-specific T-cell repertoires. Optimal procedures were identified. In particular, we compared limiting-dilution analyses (LDA) of proliferating T cells with H3-thymidine incorporation by bulk T cells and with flow cytometry CD25 expression, which is accepted as a T-cell activation marker. This study demonstrated that LDA is a reliable, predictable and sensitive method for measuring alloreactive, pathogen- and leukemia-specific T-cell frequencies. [ABSTRACT FROM AUTHOR]

T helper (Th) 17 cells have emerged as important mediators in infectious and inflammatory diseases and, recently, in transplant rejection. We analyzed the associations between five common genetic variants in the IL-23/Th17 signaling pathway, namely in IL17A, IL17F and IL23R genes, and clinical outcome in T cell-depleted allogeneic SCT (allo-SCT). In the multivariate analysis, variants in IL23R and IL17A genes were the most important prognostic factors. Thus, patient GA genotype at rs11209026 in IL23R was associated with improved overall survival (hazard ratio (HR)=0.48; P=0.028) and, in donor, with decreased risk of fungal infections (P=0.05). In contrast, patient TC and CC genotypes at rs8193036 in IL17A gene were associated with increased risk of CMV infection (HR=3.68; P=0.011) and patient acute GVHD (HR=7.08; P=0.008), respectively. These results suggest that genetic variants in the IL-23/Th17 inflammatory pathway are important prognostic factors for the clinical outcome of allo-SCT. Although validation studies are ultimately required, our results would suggest the potential usefulness of IL-23/Th17 genotyping in donor selection and patient evaluation. [ABSTRACT FROM AUTHOR]

We studied killer-cell Ig-like receptor (KIR)/natural killer (NK)-cell group-2-Ag repertoires on donor-derived NK cells in 28 patients after haploidentical SCT in the first 6 months after SCT and correlated results with EFS. The reconstitution hierarchy of potentially alloreactive, single KIR+ NK cells was the following: HLA-C1 binding>HLA-Bw4 binding>HLA-C2 binding. The differences in reconstitution kinetics of the three potentially alloreactive NK cell subsets prompted an updated analysis of EFS in AML patients transplanted from haploidentical donors in our center. This analysis showed that in haploidentical transplantation for AML, HLA-C group 1 mismatching in the graft vs host direction not only provides a survival advantage over non-NK-alloreactive (KIR ligand-matched) transplants (5-year EFS 67±10% vs 17±5%) but, indeed, also provides the best EFS compared with C2 (35±10%) or Bw4 KIR ligand mismatches (44±17%). In conclusion, we show that the kinetics with which single KIR-expressing NK cells are generated after haploidentical SCT differ between individual KIR receptors and seem to influence survival after haploidentical SCT. [ABSTRACT FROM AUTHOR]

We describe how to conduct a regression analysis for competing risks data. The use of an add-on package for the R statistical software is described, which allows for the estimation of the semiparametric proportional hazards model for the subdistribution of a competing risk analysis as proposed by Fine and Gray. J Am Stat Assoc 1999; 94: 496–509. [ABSTRACT FROM AUTHOR]

In autologous and allogeneic hematopoietic SCT (HSCT) neutropenia may be associated with severe infection. Immunodeficiency associated with GVHD and its treatment in allogeneic HSCT is also a risk for severe infection. In both periods, patients may develop severe sepsis with organ failure. To gain insights into treatment possibilities, HISTORY, a multicenter retrospective study reviewed HSCT patient records on mortality, organ dysfunction, platelet count and bleeding events. All transplantation records from 16 European centers were reviewed for 1.5 years. Of 2092 patients screened, 160 were documented for HSCT with respiratory and/or cardiovascular organ dysfunction because of sepsis and/or GVHD. Mortality was 53.1% at 28 days and 65.6% at 100 days. HSCT patients with sepsis and organ dysfunction are at highest risk of death (49.5%). Death from refractory septic shock was 15.2%, and it was 20% from respiratory failure and 64.7% from sepsis. Fewer than 3% of HSCT patients died from bleeding complications; however, individuals at increased risk of bleeding were excluded. Despite low platelet counts, an increased risk of bleeding could be established only if thrombocytopenia dropped below 13 × 109/l. Thus, there might be a therapeutic window for treatment strategies for severe sepsis in HSCT, such as drotrecogin alfa (activated).Bone Marrow Transplantation (2009) 43, 491–497; doi:10.1038/bmt.2008.337; published online 15 December 2008 [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about a simultaneous occurrence of acute myeloid leukemia with mutated nucleophosmin in the same family.

Work on one haplotype-mismatched transplants has been proceeding for over 20 years all over the world and novel transplant techniques have been developed. Some centres have focused on the conditioning regimens and post transplant immune suppression; others have concentrated on manipulating the graft. Haploidentical transplant modalities are based mainly on high-intensity conditioning regimen, but reduced intensity regimens have recently been introduced. The graft may be a megadose of extensively T cell-depleted or unmanipulated progenitor cells. Excellent engraftment rates are associated with a very low incidence of GVHD- and regimen-related mortality even in patients who are over 50 years old. Overall, event-free survival and transplant-related mortality compare favourably with reports on transplants from sources of stem cells other than the matched sibling. Improvements will come with successful implementation of strategies to accelerate and strengthen post transplant immune reconstitution as well as transplantation of patients in early stage disease.Bone Marrow Transplantation (2008) 41, 473–481; doi:10.1038/sj.bmt.1705966; published online 7 January 2008 [ABSTRACT FROM AUTHOR]

In the last decade with widespread use of quantitative analyses in medical research, close co-operation between statisticians and physicians has become essential from the experimental design through all phases of complex statistical analysis. On the other hand, easy-to-use statistical packages allow clinicians to perform basic statistical analyses themselves. Since the software they most commonly use does not perform in depth competing risk analysis, we recommend an add-on package for the R statistical software. We provide all the instructions for downloading it from internet and illustrate how to use it for analysis of a sample dataset of patients who underwent haematopoietic stem cell transplantation for acute leukaemia.Bone Marrow Transplantation (2007) 40, 381–387. doi:10.1038/sj.bmt.1705727; published online 11 June 2007 [ABSTRACT FROM AUTHOR]

In haplo-identical hematopoietic transplantation, donor vs. recipient natural killer (NK) cell alloreactivity derives from a mismatch between donor NK clones bearing inhibitory killer cell Ig-like receptors (KIR) for self-HLA class I molecules and their HLA class I ligands (KIR ligands) on recipient cells. When faced with mismatched allogeneic targets, these NK clones sense the missing expression of self-HLA class I alleles and mediate alloreactions. KIR ligand mismatches in the GvH direction trigger donor vs. recipient NK cell alloreactions, which improve engraftment, do not cause GvHD and control relapse in AML patients . The mechanism whereby alloreactive NK cells exert their benefits in transplantation has been elucidated in mouse models. The infusion of alloreactive NK cells ablates (i) leukemic cells, (ii) recipient T cells that reject the graft and (iii) recipient DC that trigger GvHD, thus protecting from GvHD. [ABSTRACT FROM AUTHOR]

Myeloablative sibling-matched allogeneic transplantation for adult acute lymphoblastic leukaemia provides the best outcome, but most patients lack a suitable, related histocompatible donor. We reviewed three haematopoietic stem cell donor sources used for alternative donor transplantation pointing out drawbacks of these approaches including inherent selection bias. Matched unrelated donor allografts most often are performed in Philadelphia chromosome-positive disease and in second complete remission (CR2); a nearly 30% event-free survival (EFS) can be anticipated in select patients. Transplants using haploidentical donors are most successful if undertaken in CR1 and CR2 and appear to produce EFS rates of about 25%. Limited umbilical cord blood transplant data suggest efficacy, but marked patient and treatment heterogeneity hamper conclusions. Each of these three strategies has unique potential benefits and disadvantages. The growing use of minimal residual disease detection may identify subgroups of patients unlikely to be cured by chemotherapy alone; these patients are candidates for upfront high-dose chemoradiotherapy and cellular immunotherapy. These three approaches are plagued by treatment-related mortality and relapse rates as high as 40%, but advances in technology and supportive care may make each stem cell source more feasible and efficacious.Bone Marrow Transplantation (2006) 38, 467–475. doi:10.1038/sj.bmt.1705464; published online 7 August 2006 [ABSTRACT FROM AUTHOR]

Premise: Since March 1993, 133 patients with high-risk acute leukemia (66 AML, 67 ALL) have received a megadose of T-cell depleted hematopoietic stem cells. The 1993-95 conditioning protocol included TBI, thiotepa, ATG and CY for 36 patients who received an inoculum made up of lectin-separated bone marrow and PBPCs. After 1995, to minimise the extra-hematological toxicity of the conditioning and eliminate GvHD, we substituted fludarabine for CY in the conditioning and PBPCs were depleted of T-cells by a positive selection of the CD34+ cells using CellPro (n=44 patients) or, since January 1999, CliniMacs (n = 53 patients). A later modification to the protocol in January 1999 was the suspension of post transplant G-CSF. WORK IN PROGRESS: We report here the results in the last 53 acute leukemia patients all of whom were transplanted under our modified protocol. Ages ranged from 9 to 62 years with a median of 38 years for the 33 patients with AML and 23 for the 20 with ALL. All were at high risk because 25 were actually in relapse at transplant, 16 were in second or later CR and even the 12 patients in CR1 were at high risk because of the unfavourable prognostic features. Overall 52/53 patients (98%) engrafted. The TBI-Fludarabine-based conditioning was well tolerated even in the 14 patients between 45 and 62 years of age. There was no veno-occlusive disease of the liver and the incidence of severe mucositis was low. Even though no post-transplant immunosuppressive therapy was given, acute GvHD grade > or = II occurred in only 4 cases and only one progressed to chronic GvHD. Overall, 16 patients (30%) have died of non-leukemic causes. Relapses occurred mainly in patients who were already in relapse at transplant (12/25). Only 3 of the 28 who were in any CR at transplant have so far relapsed. As our group has already shown, donor-vs-recipient NK cell alloreactivity exerts a specific graft-vs-AML effect in the absence of GvHD. In fact, leukemia relapse was largely controlled in AML recipients whose donor was NK alloreactive, with only 2 out of 16 relapsing. To date, 13 of 18 AML (72%) and 5 of 10 ALL (50%) who were in any CR at transplant, survive disease-free while 4 of the 15 patients (16%) in relapse at transplant survive. The probability of event-free survival for patients transplanted in CR is 60% in the 18 AML patients and 38% in the 10 ALL. The probability of EFS was significantly better in the 16 AML patients whose transplant included donor vs recipient NK cell alloreactivity than in those whose transplant did not (70% vs 7%). In conclusion, given our current results, the most suitable candidate for the full haplotype mismatched transplant should be in early stage disease and selection of an NK alloreactive donor is recommended. [ABSTRACT FROM AUTHOR]

Background: Allogeneic hematopoietic transplantation relies on T-cell alloreactions for engraftment and the GvL effect. In HLA haplotype-mismatched transplants, extensive T-cell depletion of the graft is essential to prevent GvHD. This raises the question of whether mismatched transplants exert any GvL effect, and whether it will ever be possible to reduce the intensity of preparative regimens. Natural killer (NK) cells are negatively regulated by MHC Class I-specific inhibitory receptors. Mismatched transplants may therefore trigger NK-cell alloreactivity. Methods: The effects of NK-cell alloreactivity were evaluated in clinical transplantation and in murine transplant models. Results: In clinical hematopoietic stem-cell transplants, HLA Class I disparities driving NK-cell alloreactions in the GvH direction eliminate AML relapse and graft rejection, while protecting patients from GvHD. In murine MHC mismatched transplant models, the pre-transplant infusion of donor-versus-recipient alloreactive NK cells conditioned the recipients to BMT, and reduced GvHD. Discussion: NK-cell alloreactivity may thus provide a novel, powerful tool for enhancing the efficacy and safety of allogeneic hematopoietic transplantation. [ABSTRACT FROM AUTHOR]

Examines the risk and risk factors for cataract formation in several patients receiving two different total body irradiation (TBI) schedules in their pre-transplant regimen. List of risk factors for cataract formation; Probability estimates of developing cataract according to the TBI scheme and kind of transplant; Factors that influence cataract formation in patients that received single-dose TBI.

Clinical trials have shown that a strategy for haploidentical transplantation based on the infusion of high numbers of T-cell-depleted hematopoietic progenitor cells and no post-transplant immunosuppression controls graft rejection and GvHD in patients with acute leukemia. Overall, event-free survival compares favorably with reports of transplants using sources of stem cells other than the matched sibling. Current studies are focussing on rebuilding post-transplant immunity to improve clinical outcomes separating GvHD from favourable donor immune responses. [ABSTRACT FROM AUTHOR]

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We present a detailed description of O(α) inclusive jet cross-sections for finite cone sizes and give the explicit depedence on the cone opening angle, which is absent at the Born level. Other phenomenological implications are also discussed. [ABSTRACT FROM AUTHOR]

We present the full 0( α) QCD corrections to jet production within a small opening angle δ at large transverse momenta for all partonic subprocesses. Results for CERN and Tevatron colliders are given with particular emphasis on the sensitivity to renormalization and factorization mass scales. [ABSTRACT FROM AUTHOR]

The article discusses research which examined the pediatric hematology patients treated off-label with posaconazole from March 1, 2008- May 30, 2009. The study showed that the assessment of efficacy after 90 days of posaconazole has a significant clinicalradiological improvement in nine patients. Further, it revealed that such treatment may represent an alternative choice for the prophylaxis and therapy of pediatric patients with fungal infections.

The article presents the discussion on Haploidentical Transplants which being the new forms of transplantation. Topics include showing the infusion of very large hematopoietic stem cell dose being fundamental in promoting engraftrnent across HLA-barriers; and Tiibingen group achieving a high rate of primary engraftment in children with acute leukaemia; and becoming a major criterion for donor selection in mismatched hematopoietic stem cell transplants.

A correction to the article "In haematopoietic SCT for acute leukemia TBI impacts on relapse but not survival: results of a multicentre observational study," published online on May 27, 2013 is presented.