Lower expression of NOTCH components in peripheral blood mononuclear cells of allogeneic hematopoietic cell transplant patients

ABSTRACT Introduction: Chronic graft-versus-host disease (cGvHD) not only remains the main cause of late mortality after allogeneic hematopoietic cell transplant, but also has the capacity of causing severe organ impairment in those who survive. The Notch, a highly conserved ligand-receptor pathway, is involved in many immunological processes, including inflammatory and regulatory responses. Recently, mouse models have shown that the blockage of canonical Notch signaling prevents GvHD. Objective and Method: Due to the lack of data on the Notch pathway in human chronic GvHD, we sought to study the expression of NOTCH components in primary samples of patients who received allo-HCT and presented active cGvHD or a long-term clinical tolerance to cGvHD. Results: Our results showed a significantly lower expression of NOTCH components in both groups that received allo-HCT, independently of their cGvHD status, when compared to healthy controls. Conclusion: Moreover, there were no differences in gene expression levels between the active cGvHD and clinically tolerant groups. To our knowledge, this is one of the first studies performed in human primary samples and our data indicate that much remains to be learned regarding NOTCH signaling as a new regulator of GvHD.

Favorable long-term survival using consolidation chemotherapy without allogeneic hematopoietic cell transplantation for acute myeloid leukemia with wild-type NPM1 without FLT3-ITD

BACKGROUND: The role of allogeneic hematopoietic cell transplantation (allo-HCT) compared with consolidation chemotherapy alone in intermediate-risk acute myeloid leukemia (AML) patients with wild-type nucleophosmin/negative or a low level of Fms related tyrosine kinase 3 internal tandem duplication (NPM1(wt)/FLT3-ITD(neg/low)) has not yet been elucidated. METHODS: In this study, we retrospectively investigated 88 patients newly diagnosed with AML who received intensive induction chemotherapy at Kyungpook National University Hospital from March 2015 to July 2017. The selection criteria included the presence of results on genetic abnormalities including NPM1 and FLT3-ITD. RESULTS: According to the European LeukemiaNet (ELN) risk classification, 25 patients (28%) were categorized as favorable, 44 (50%) as intermediate, and 19 (22%) as adverse risk. Among the intermediate-risk patients, 40 were identified as NPM1 wt/FLT3-ITDneg/low. Among the patients with NPM1(wt)/FLT3-ITD(neg/low), complete remission (CR) was achieved in 26 patients out of 40 (65%). One-year overall survival (OS) rate was 100% in the favorable-risk group and 87.9% in the NPM1(wt)/FLT3-ITD(neg/low) group (P=0.233). Among the intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients, there was no survival benefit with allo-HCT (N=19) compared to consolidation chemotherapy (N=21; P=0.372). In the multivariate analysis, the ELN risk group [hazard ratio (HR), 6.36; P=0.019] and the achievement of CR (HR, 2.95; P=0.017) were both identified as factors affecting OS of patients with newly diagnosed AML. CONCLUSION: Among the AML patients, intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients and favorable-risk patients showed similar OS rates. Our results suggested that allo-HCT might have limited clinical benefit for the intermediate-risk NPM1(wt)/FLT3-ITD(neg/low) patients. Well controlled studies are needed to confirm the current results.

Trasplante de médula ósea alogénico en un paciente con fusariosis diseminada y leucemia mieloide aguda / Allogeneic hematopoietic cell transplantation in a patient with disseminated fusariosis and acute myeloid leukemia

La infección diseminada por Fusarium se ha convertido en un problema creciente en las personas con neoplasias hematológicas malignas, principalmente en pacientes con leucemias agudas; se describen cada vez más casos en aquellos sometidos a un trasplante de médula ósea. No existe un tratamiento óptimo establecido para la fusariosis diseminada. La mortalidad global comunicada de esta infección oscila entre el 50 y el 80%. Se presenta a continuación el caso de un paciente de sexo masculino de 29 años, con diagnóstico de leucemia mieloide aguda, que presenta como complicación una fusariosis diseminada, y logra sobrellevar un trasplante alogénico de médula ósea en el Hospital Italiano de San Justo (Argentina) de forma exitosa. (AU)

Disseminated fusariosis has become an increasing problem in people with hematopoietic neoplasms, mainly in patients affected by acute leukemias, and even more in those who undergo hematopoietic cell transplantation. There is not an optimal treatment for disseminated fusariosis. The global mortality described in the literature is between 50% and 80%. We introduce a case of a 29 year old patient with diagnosis of acute myeloid leukemia complicated with disseminated fusariosis, who copes with an allogeneic hematopoietic cell transplantation with a successful outcome in the "Hospital Italiano de San Justo" (Argentina). (AU)

Brain Imaging and Overall Survival after Allogeneic Hematopoietic Cell Transplantation.

Aim: We conducted a retrospective review of all brain imaging studies in the first year after allogeneic haematopoietic cell transplantation (HCT) to determine (a) the percentage of patients with CNS neurological complications based solely on undergoing brain imaging, (b) transplant-related risk factors of undergoing brain imaging, and (c) overall survival in the patients with neurological complications compared to those transplant patients who did not have brain imaging. Methods: Subjects were 543 consecutive recipients (August 2004-August 2007) of allogeneic HCT followed for overall survival for up to 6 years after HCT. Comparisons between patient groups with brain imaging and without brain imaging were tested using the Pearson chi-square test. Survival analyses with outcome time-to-brain-scan started at date of transplant and used Kaplan-Meier methods. Results: Of 543 HCT recipients, 128 patients (24%) underwent brain imaging during the first year after transplantation. There was a greater risk of brain imaging in unrelated donor transplants and in lymphoid as opposed to myeloid malignancies (respective hazard ratios 1.45 and 1.43, P=0.04). Overall survival was significantly worse in unrelated donor transplants (hazard ratio 1.42, P=0.003) and in cord blood transplants (hazard ratio 1.68, P=0.02). Landmark survival analysis of patients alive 1 year after HCT showed worse survival over the next 5 years in those who had brain imaging in the first post transplant year (P<0.0001). Conclusion: These results suggest that development of neurological symptoms or a sign sufficient to prompt clinicians to order brain imaging early after HCT identifies a poor prognosis in transplant population.

Infectious Complications after Monoclonal Antibody Therapy in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients / 임상소아혈액종양

BACKGROUND: We evaluated characteristics of infectious complications in pediatric patients who received monoclonal antibody (mAb) therapy after allogeneic hematopoietic cell transplantation (HCT). METHODS: Between February 2004 and May 2009, 17 pediatric patients (<19 years at diagnosis) who received mAbs were identified as a study group (mAb group). One hundred twenty-two pediatric allogeneic HCT patients (<19 years at diagnosis) who did not receive mAb during the same period were identified as a control group (non-mAb group). A retrospective chart review of medical records was performed for the incidence of infectious complications and mortality. RESULTS: In the mAb group, 12 of the 17 patients (70.6%) had 29 infectious complications (1.71 episodes per person), whereas 89 of the 122 patients (73.8%) had 162 infectious complications (1.32 episodes per person) in the non-mAb group (P=0.838). Although, there were no significant differences in characteristics or incidence of infectious complications between the two groups, the infection-associated mortality rate was significantly higher in the mAb group compared to non-mAb group (29.4% vs. 8.2% P=0.021; RR 3.44, 95% CI, 1.407 to 8.433). CONCLUSION: The mAb therapy was associated with significantly high mortality in pediatric allogeneic HCT recipients.

Infectious Complications after Monoclonal Antibody Therapy in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients / 임상소아혈액종양

BACKGROUND: We evaluated characteristics of infectious complications in pediatric patients who received monoclonal antibody (mAb) therapy after allogeneic hematopoietic cell transplantation (HCT).METHODS: Between February 2004 and May 2009, 17 pediatric patients (<19 years at diagnosis) who received mAbs were identified as a study group (mAb group). One hundred twenty-two pediatric allogeneic HCT patients (<19 years at diagnosis) who did not receive mAb during the same period were identified as a control group (non-mAb group). A retrospective chart review of medical records was performed for the incidence of infectious complications and mortality.RESULTS: In the mAb group, 12 of the 17 patients (70.6%) had 29 infectious complications (1.71 episodes per person), whereas 89 of the 122 patients (73.8%) had 162 infectious complications (1.32 episodes per person) in the non-mAb group (P=0.838). Although, there were no significant differences in characteristics or incidence of infectious complications between the two groups, the infection-associated mortality rate was significantly higher in the mAb group compared to non-mAb group (29.4% vs. 8.2% P=0.021; RR 3.44, 95% CI, 1.407 to 8.433).CONCLUSION: The mAb therapy was associated with significantly high mortality in pediatric allogeneic HCT recipients.