s6 kinase br Contribution br Acknowledgments and disclosures

Contribution
Acknowledgments and disclosures
Introduction Following HSCT a complex immune reconstitution (IR) is observed. When the infused CD34+cells (CD34+i) begin to proliferate, an increase in peripheral blood s6 kinase is detected. Lymphocytes require more time than granulocytes in order to reestablish their normal function during the early post-transplant period [1]. An absolute lymphocyte count (ALC) >500/μl at day 15 post-HSCT has been associated with a better prognosis in patients with hematologic malignancies [2–4]. Moreover, the number of CD34+i has been associated with ALC and clinical evolution. Hence, an ALC≤500/μl on day 15 has been proposed as an independent risk factor [3–6]. Our aim was to determine the influence of ALC, at day 15, in predicting post-HSCT outcome in patients with non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and multiple myeloma (MM) in terms of progression-free survival (PFS) and overall survival (OS), and to analyze the relationship between the number of CD34+i and the number of days required in order to reach ALC≥500/μl as well as clinical evolution.
Materials and methods
Discussion In accordance with the results, we have been able to determine the existence of several factors with an impact on outcome after autologous HSCT. Additional variables have been reported [5–7] but detailed description of every single prognostic factor apparently involved in post-transplant evolution was beyond the scope of this study. In accord with other authors [3–7], patients in our study with localized disease at diagnosis showed better outcome compared to those whose disease was in an advanced stage. Furthermore, patients in CR1 or CR2 pre-HSCT showed better survival rates than those who presented with disease progression. Nevertheless, in contrast with other authors [6,7], there did not seem to be any significant difference in prognosis between patients in PR and those who achieved CR2 pre-HSCT. Porrata et al. were the first to describe prognostic significance of early ALC in patients with HM undergoing HSCT [2–5] and we confirmed that. Some authors have attributed this improvement in survival to a decrease in infection susceptibility in the subgroup of patients who managed to attain an early lymphocytic reconstitution (ELR) after HSCT [1,2]. Even though we did not specifically analyze infection risk in our patients, we proposed that such a relation can be responsible for this observation. Developing a means to predict ELR (to express as ALC) after HSCT could be of great use during transplantation. In order to try to prove this point, we obtained a predictive model capable of estimating total days for ELR according to CD34+i at day 0. Late ALC (after day 15) can probably be associated with a greater incidence of infections due to impaired immunity and, hence, a worse prognosis [6–8]. Consequently, pre-transplant knowledge of lymphocyte reconstitution dynamics should be able to define which subgroup of patients could benefit from early antibiotic therapy, and which optimal CD34+i count should be reached in order to guaranty ELR. In this sense, we propose early ALC as a predictive prognostic marker. Additionally, we found a positive correlation between CD34+i and dynamics of lymphocyte recovery, especially in patients with HL. We have obtained a regression line as a predictive model of lymphocyte recovery, not previously described, based on CD34+i and it could be used as a prognosis tool in this patients. Nonetheless, future prospective studies analyzing lymphocyte subpopulations are needed to achieve a better understanding of IR. There are still many questions that remained unanswered.
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Authors\' contributions
Acknowledgments
Introduction Chronic myelogenous leukemia (CML), a rare disease in children and young people, is a myeloproliferative neoplasm consistently associated with the BCR-ABL fusion gene. The oncoprotein BCR-ABL, deranges the balance of cell growth and death in normal hematopoietic cells. The BCR-ABL tyrosine kinase (TK) inhibitor, imatinib mesylate (IM), is an effective treatment for CML. Although IM inhibits TKs associated with specific diseases, in vivo inhibition of PDGF receptor and c-kit may also occur and may have clinical consequences. IM is well tolerated and molecular remission can be achieved in children and adults. However, altered bone and mineral metabolism [1,2] and severe oligozoospermia [3] in patients taking IM before puberty, and reduction of testosterone and gynecomastia [4], thyreopathy [5] and other endocrinological disorders in a proportion of adult patients has been reported [6].