Lal Bahadur Nagar, India
Lal Bahadur Nagar, India

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Grioni D.,University of Milan Bicocca | Pavan F.,BMT Unit | Prunotto G.,BMT Unit | Canonico F.,University of Milan Bicocca | And 2 more authors.
Neuropediatrics | Year: 2017

Despite a wide number of studies trying to define clinical, physiopathological, and neuroradiological features of posterior reversible encephalopathy syndrome (PRES), the true nature of symptoms is still not fully understood. We studied a standard cohort of 24 pediatric patients, affected by hemato-oncological diseases, with a neuroradiological diagnosis consistent with PRES identified from 2006 to 2013. Ten of them developed PRES after hematopoietic stem cell transplantation. We analyzed the sequence of clinical, radiological, and electrophysiological data. In all the patients who were recorded at the onset of the first symptoms, electroencephalograms showed focal nonconvulsive seizures or status epilepticus (SE). We found a sensitivity of 100% for electroencephalogram (EEG) with a good correlation between clinical signs and the localization of seizures, whereas computed tomography scans showed a sensitivity of 50% only. Following prompt treatment, intensive care unit admission rate was only 8%. PRES is a multifactorial neurologic event with focal nonconvulsive seizures or SE as the main feature in pediatric patients. Clinical manifestations are epileptic in nature, and prompt EEG recording is useful for diagnosis and supports an earlier treatment, potentially preventing the appearance of complications such as generalized seizures or refractory SE. © Georg Thieme Verlag KGStuttgart · New York.


Wachowiak J.,Poznan University of Medical Sciences | Chybicka A.,Oncology and BMT | Gorczyska E.,Oncology and BMT | Grund G.,Poznan University of Medical Sciences | Peters C.,BMT Unit
Bone Marrow Transplantation | Year: 2011

This retrospective analysis evaluated 51 children (0.7-17 years; median eight) with high-risk or advanced hematological malignancies, including 18 (35%) patients undergoing second/third hematopoietic SCT (allo-HSCT), not eligible for standard myeloablative regimens and transplanted from matched sibling (MSD) (n24) or matched unrelated (MUD) (n27) donors. Preparative regimens were based on treosulfan (TREO) i.v., a structural analog of BU, given at total dose of 30 g/m 2 (n21) or 36-42 g/m 2 (n30) in combination with, fludarabine, cyclophosphamide, melphalan and/or VP-16 according to diagnosis, and risk factors. Deaths due to early regimen-related toxicity (RRT) did not occur. Nonrelapse mortality was 8% at 1 year and 16% after 4 years. Myeloid engraftment was achieved in 94%, complete donor chimerism in 90% of patients. A 4-year incidence of relapse was 24%, and was significantly lower after MUD-HSCT (8%) than after MSD-HSCT (39%), but similar in children undergoing first (28%) or second/third HSCT (17%). A 4-year disease-free survival was 61%, but it was significantly better in myeloid (73%), than in lymphoid malignancies (41%). Thus, children with high-risk and advanced hematological malignancies and high-risk of life-threatening RRT can be transplanted effectively and safely using TREO-based regimens. Particularly favorable results were achieved in myeloid malignancies and in children undergoing second HSCT. © 2011 Macmillan Publishers Limited.


Passweg J.R.,University of Basel | Baldomero H.,University of Basel | Bregni M.,San Raffaele Scientific Institute | Cesaro S.,Paediatric Haematology Oncology | And 12 more authors.
Bone Marrow Transplantation | Year: 2013

In all, 651 from 680 centers in 48 countries reported 35 660 hematopoietic SCT (HSCT) in 32 075 patients (13 470 allogeneic (42%), 18 605 autologous (58%)) to the 2011 survey. Main indications were: leukemias; 10 113 (32%; 94% allogeneic); lymphoid neoplasias; non-Hodgkin's lymphoma, Hodgkin's lymphoma, plasma cell disorders; 18 433 (57%; 12% allogeneic); solid tumours; 1573 (5%; 5% allogeneic); and non-malignant disorders; 1830 (6%; 92% allogeneic). There were more unrelated donors than HLA identical sibling donors (54% versus 39%); proportion of peripheral blood as stem cell source was 99% for autologous and 73% for allogeneic HSCT. Cord blood was only used in allogeneic transplants (6% of total). In the past 10 years, the overall number of transplants has increased by 53%. Allogeneic HSCT have doubled (from 7272 to 14 549) while, autologous have increased by 32% and continue to increase by about 1100 HSCT per year since 2001. In the past 2 years, an increase of >2000 HSCT per year was seen. Transplant activity is shown by team size. For allogeneic HSCT, we show use of reduced-intensity conditioning versus myeloablative conditioning across Europe and use of post-transplant donor lymphocyte infusions with considerable variation across different countries. © 2013 Macmillan Publishers Limited.


Passweg J.R.,University of Basel | Baldomero H.,University of Basel | Peters C.,BMT Unit | Gaspar H.B.,University College London | And 13 more authors.
Bone Marrow Transplantation | Year: 2014

In all, 661 of 680 centers in 48 countries reported 37 818 hematopoietic SCT (HSCT) in 33 678 patients (14 165 allogeneic (42%), 19 513 autologous (58%)) in the 2012 survey. Main indications were leukemias, 10 641 (32%; 95% allogeneic); lymphoid neoplasias, 19 336 (57%; 11% allogeneic); solid tumors, 1630 (5%; 3% allogeneic); and nonmalignant disorders, 1953 (6%; 90% allogeneic). There were more unrelated donors than HLA-identical sibling donors (54% versus 38% (8% being mismatched related donor HSCT)). Cord blood was almost exclusive in allogeneic transplants (5% of total). Since 2011, the highest increases in allogeneic HSCT were for AML in CR1 (12%) and for myeloproliferative neoplasm (15%). For autologous HSCT the main increases were for plasma cell disorders (7%), non-Hodgkin lymphoma (4%) and autoimmune disease (50%). There were 4097 pediatric patients <18 years of age receiving HSCT, 2902 received an allogeneic and 1195 an autologous HSCT. Overall, 69% of allogeneic and 64% of autologous HSCT were performed in dedicated pediatric centers and the remainder in combined adult and pediatric centers. Distributions of diseases, donor types and stem cell source for all patients and pediatric patients in particular are shown. A percentage of centers fulfilling the annual required criteria for patient numbers for JACIE accreditation are provided. © 2014 Macmillan Publishers Limited. All rights reserved.


Gallamini A.,BMT Unit | Kostakoglu L.,Mount Sinai Medical Center
Blood | Year: 2012

Despite the rewarding results achieved in the treatment of Hodgkin lymphoma (HL), concerns have been raised regarding the long-term complications induced by therapy. Hence, the current challenge is to develop a new therapeutic strategy maintaining excellent patient outcome while reducing potentially life-threatening late adverse effects. Therefore, it would be beneficial to identify chemoresistant or refractory patients early during therapy for appropriate and timely escalation of treatment. Recently, compelling data have emerged on the prognostic role of interim [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) performed early during the course of treatment to predict ultimate outcome, even proving superior to conventional prognostic factors. Several ongoing prospective trials are exploring the feasibility of treatment de-escalation strategies in patients with a negative interim PET, as well as therapy escalation in advanced-stage HL patients who have a positive interim PET result. In this article, the published reports on the contribution of interim PET to the design of ongoing response-adapted clinical trials are reviewed. Moreover, some of the unresolved issues revolving around the suboptimal positive predictive value of interim PET are addressed with an emphasis on the interpretation criteria.Afinal remark on the appropriate use of interim PET is also provided. © 2012 by The American Society of Hematology.


Wiskemann J.,Central Institute of Mental Health | Wiskemann J.,German Cancer Research Center | Dreger P.,University of Heidelberg | Schwerdtfeger R.,BMT Unit | And 6 more authors.
Blood | Year: 2011

Before, during, and after allogeneic hematopoietic stem cell transplantation (allo-HSCT), patients experience considerable physical and psychologic distress. Besides graft-versus-host disease and infections, reduced physical performance and high levels of fatigue affect patients' quality of life. This multicenter randomized controlled trial examined the effects of a partly self-administered exercise intervention before, during, and after allo-HSCT on these side effects. After randomization to an exercise and a social contact control group 105 patients trained in a home-based setting before hospital admission, during inpatient treatment and a 6- to 8-week period after discharge. Fatigue, physical performance, quality of life, and physical/psychologic distress were measured by standardized instruments at baseline, admission to, and discharge from hospital and 6 to 8 weeks after discharge. The exercise group showed significantly improvement in fatigue scores (up to 15% improvement in exercise group vs up to 28% deterioration in control; P < .01-.03), physical fitness/functioning (P = .02-.03) and global distress (P = .03). All effects were at least detectable at one assessment time point after hospitalization or repeatedly. Physical fitness correlated significantly with all reported symptoms/variables. In conclusion, this partly supervised exercise intervention is beneficial for patients undergoing allo-HSCT. Because of low personnel requirements, it might be valuable to integrate such a program into standard medical care. © 2011 by The American Society of Hematology.


Lazana I.,BMT Unit | Zoudiari A.,BMT Unit | Kokkinou D.,BMT Unit | Themeli M.,BMT Unit | And 4 more authors.
Haematologica | Year: 2012

The human leukocyte antigen-G (HLA-G) has been considered to be an important tolerogeneic molecule playing an essential role in maternal-fetal tolerance, which constitutes the perfect example of successful physiological immunotolerance of semi-allografts. In this context, we investigated the putative role of this molecule in the allogeneic hematopoietic cell transplantation setting. Design and Methods The percentage of HLA-G + cells in peripheral blood of healthy donors and allo-transplanted patients was evaluated by flow cytometry. Their immunoregulatory and tolerogeneic properties were investigated in in vitro immunostimulatory and immunosuppression assays. Immunohistochemical analysis for HLA-G expression was performed in skin biopsies from allo-transplanted patients and correlated with the occurrence of graft-versus-host disease. Results We identified a CD14 +HLA-G pos population with an HLA-DR low phenotype and decreased in vitro immunostimulatory capacity circulating in peripheral blood of healthy individuals. Naturally occurring CD14 +HLA-G pos cells suppressed T-cell responses and exerted an immunotolerogenic action on T cells by rendering them hyporesponsive and immunosuppressive in vitro. After allogeneic hematopoietic cell transplantation, HLA-G pos cells increase in blood. Interestingly, besides an increase in CD14 +HLA-G pos cells, there was also a pronounced expansion of CD3 +HLA-G pos cells. Of note, CD3 +HLA-G pos and CD14 +HLA-G pos cells from transplanted patients were suppressive in in vitro lymphoproliferation assays. Furthermore, we found an upregulation of HLA-G expression in skin specimens from transplanted patients that correlated with graft-versus-host disease. Inflammatory cells infiltrating the dermis of transplanted patients were also HLA-G pos. Conclusions We report the presence of naturally occurring HLA-G pos monocytic cells with in vitro suppressive properties. HLA-G expressing regulatory blood cells were found in increased numbers after allogeneic transplantation. Epithelial cells in skin affected by graft-versus-host disease revealed elevated HLA-G expression. ©2012 Ferrata Storti Foundation.


Meignan M.,Lymphoma Unit | Gallamini A.,BMT Unit | Haioun C.,Lymphoma Unit | Polliack A.,Hebrew University of Jerusalem
Leukemia and Lymphoma | Year: 2010

One hundred and fifty hemato-oncologists and nuclear medicine specialists from more than 20 countries joined in April 2010 the 2-day Second International Workshop on interim PET in lymphoma. During the nuclear medicine session the advantages of the five-point scale Deauville criteria for interim PET reporting over the other sets of visual criteria were presented. The specific problems of PET reporting in escalationde-escalation trials in Hodgkin lymphoma HL were addressed as well as the limitations of visual analysis for early PET evaluation in non-Hodgkin lymphoma NHL. The applicability, efficacy, and reproducibility of quantitative criteria ΔSUV max analysis and tumorliver SUV ratio for interim PET in NHL were reported. In retrospective and prospective series. Some of the interim PET-based clinical trials ongoing worldwide in HL and NHL were reported. In early-stage HL, three trials aimed at determining the feasibility of omitting radiotherapy in interim PET negative patients, and in advanced-stage HL two PET-based ABVD escalation or BEACOPP de-escalation trials, in NHL two studies reported preliminary results of interim PET in follicular lymphoma, in DLBCL a round-table discussion pointed out the lack of definite criteria for interim PET, and a few observational studies in DLBCL reported the comparison of the various techniques of interim PET reporting visual versus quantitative. The preliminary results of two international validation studies of the five-point scale criteria in HL and NHL launched in 2009 were reported. The presentations of the meeting are available on http://eitti.free.fr © 2010 Informa UK, Ltd.


Chevallier P.,Nantes University Hospital Center | Labopin M.,University Pierre and Marie Curie | Milpied N.,Bordeaux University Hospital Center | Cornelissen J.J.,Erasmus Daniel Den Hoed Cancer Center | And 7 more authors.
Bone Marrow Transplantation | Year: 2012

So far the impact of cytogenetics risk on outcome in the context of reduced intensity conditioning (RIC) allo-SCT has been poorly studied. We have identified 378 AML patients in first CR who underwent RIC allo-SCT from an HLA-matched sibling donor between 2000 and 2007 reported to the European Group for Bone and Marrow Transplantation and for whom detailed cytogenetics data were available (good risk: n21; intermediate risk: n304; and poor risk: n53). With a median follow-up of 24 months (range: 193), 2-year non-relapse mortality, relapse rate (RR), leukemia-free survival (LFS) and OS were 14%, 31%, 55% and 61%, respectively. Cytogenetics was significantly associated with RR (good risk: 10%; intermediate risk: 28%; and poor risk: 55% at 2 years, P0.0001) and LFS (good risk: 64%; intermediate risk: 57%; and poor risk: 38% at 2 years, P0.003). In a multivariate analysis, RR and LFS were significantly higher and lower, respectively, in the high-risk cytogenetics group (P0.001, P0.004) and in patients with a higher WBC at diagnosis (>10 × 109/L) (P<0.001, P<0.004). As documented in the setting of myeloablative allo-SCT, patients with poor cytogenetics had increased RR and decreased LFS after RIC allo-SCT, requiring new prospective strategies to improve results in this subgroup. © 2012 Macmillan Publishers Limited All rights reserved.


PubMed | Tel Aviv University, Hadassah Medical Center, BMT Unit and Rambam Health Care Campus
Type: | Journal: Annals of hematology | Year: 2017

Elderly and infirm patients with acute myeloid leukemia (AML) with either induction refractory or relapse disease may benefit from treatment with azacitidine. We retrospectively reviewed the data from five tertiary centers in Israel, treated between 2009 and 2015. Thirty-four patients (median age 74years) were identified. Sixty-two percent of the patients had relapsed disease and 38% had refractory disease. Median time of follow-up was 12.1months. Out of a total of 327 courses, incidence of infectious episodes was 6%. Eighteen percent experienced major bleeding. Thirty-two percent of the patients achieved morphologic complete remission, and 26% had stabilization of disease during at least three courses. At 12 and 18months after the first course of azacitidine, 33 and 10% of the patients were progression-free, respectively. Incidences of overall survival at 12 and 24months were 54.5 and 16%, respectively. Age <75years was associated with better overall survival. Normal leukocyte count at the first dose of azacitidine and standard doses of azacitidine were both associated with a better progression-free and overall survival. We conclude that azacitidine is feasible in patients who have failed induction chemotherapy and may be associated with prolongation of survival. A prospective trial to validate these results is warranted.

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