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  • 1
    Publication Date: 2019-03-19
    Description: Background: Improved outcome prediction is vital for the delivery of risk-adjusted, appropriate and effective care to paediatric patients with Ewing sarcoma—the second most common paediatric malignant bone tumour. Fourier transform infrared (FTIR) spectroscopy of tissues allows the bulk biochemical content of a biological sample to be probed and makes possible the study and diagnosis of disease. Methods: In this retrospective study, FTIR spectra of sections of biopsy-obtained bone tissue were recorded. Twenty-seven patients (between 5 and 20 years of age) with newly diagnosed Ewing sarcoma of bone were included in this study. The prognostic value of FTIR spectra obtained from Ewing sarcoma (ES) tumours before and after neoadjuvant chemotherapy were analysed in combination with various data-reduction and machine learning approaches. Results: Random forest and linear discriminant analysis supervised learning models were able to correctly predict patient mortality in 92% of cases using leave-one-out cross-validation. The best performing model for predicting patient relapse was a linear Support Vector Machine trained on the observed spectral changes as a result of chemotherapy treatment, which achieved 92% accuracy. Conclusion: FTIR spectra of tumour biopsy samples may predict treatment outcome in paediatric Ewing sarcoma patients with greater than 92% accuracy.
    Electronic ISSN: 1420-3049
    Topics: Chemistry and Pharmacology
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  • 2
    Publication Date: 2008-11-16
    Description: The incidence of cadiotoxicity (CT) has been estimated at 5–10% of adult patients following hematopoietic stem cell transplantation (HSCT), but it is unknown in patients undergoing HSCT in childhood. Recent studies showed several biochemical markers as potentially useful for early detection of CT: Atrial Natriuretic Peptide (ANP) secreted by the atria in response to stretch as a result of an increased left atrial pressure, N-terminal fragment of Brain Natriuretic Peptide (NT-proBNP) produced by ventricles in response to ventricular dilatation and increased wall stress, cardiac Troponin I (TnI) the thin-filament contractile protein released to the circulation after myocardial injury and Endothelin 1 (ET-1) a vasoconstrictor peptide synthesized in the vasculature and by the endothelial cells and ventricular myocytes. The aim of the study was to assess the frequency and significance of elevated NT-proBNP, ANP, ET-1 and TnI plasma levels and their correlation to echocardiographic parameters of left ventricular function: shortening fraction (FS) and ejection fraction (EF) in children in early postransplant period. Patients: A total number of 31 consecutive children (22 boys and 9 girls) with median age of 9.6 years (range 0–18), treated with HSCT were included in the study: 12 autologous (aHSCT), 9 unrelated donor (MUD HSCT) and 10 family donor (MSD HSCT) transplantations were performed. The control group consisted of 14 healthy children, with median age of 10.9 years. Methods: The plasma levels of NT-proBNP, ANP and ET-1 were measured in transplanted patients on days −7, 0, +7, +14 by the Electrochemiluminescent Immunoassay (Biomedica) and TnI by the Immunoassay (Abbot). SF and EF were assessed by echocardiography prior to HSCT and about day +30 and +100 after transplantation. The same tests were performed in the control group. Results: Baseline echocardiographic parameters were within the normal range in all patients included in the study. In comparison with a control group, a trend to decrease median SF and EF values was observed on day +30 (FS 〉 28% and EF 〉 55%). In transplanted patients median ET-1 plasma levels were elevated in all analyzed time points when compared to controls (p〈 0.05); median NT pro-BNP plasma concentrations were significantly elevated from days −7 to +7 (p〈 0.05) and median ANP plasma concentrations on day +7 (p〈 0.05). Median levels of TnI did not differ between analyzed and control groups. No correlation was found between elevated biochemical marker levels and echocardiographic parameters evaluated on days +30 and +100 after HSCT. According to the type of transplant, in aHSCT patients ET-1 plasma level elevation was observed in 4 analyzed time points (p〈 0.05), while in MUD transplant recipients on day +7 only and in MSD transplant recipients on day +14 only. NT pro-BNP and ANP plasma levels were elevated in MUD transplant recipients on days 0,+7, +14 (p
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  • 3
    Publication Date: 2006-11-16
    Description: Recent data suggest that oxidative-antioxidative imbalance may influence cytokine secretion in children with acute lymphoblastic leukemia (ALL). Plasma cytokines concentrations are reported to have an effect on clinical course of the patients with lymphoid malignancies. The aim of the study was analysis of oxidative status (Malonylodialdehyde, MDA) and antioxidant defense (Superoxide dismutase, SOD; glutathione peroxidase, GPX; total antioxidant status, TAS and vitamin E) in peripheral blood and evaluation of plasma concentration of IL-2, IL-4, IL-10 and TNF-alpha in children with acute lymphoblastic leukemia. Material and methods: Study group consisted of 23 newly diagnosed ALL children, including 13 boys and 10 girls, with median age 5 years (range, 0.5–16). Control group consisted of 21 healthy children (11 boys and 7 girls) with median age 7 years (range, 2–17). TAS, SOD, GPX status were estimated using commercially available Randox Laboratories Ltd kits. Vitamin E and MDA plasma concentrations were measured spectrofluorimetrically. Cytokine concentrations were measured by quantitative immunoassay tests: IL-2 and IL-4 plasma levels were assessed using Bender MedSystems test (Vienna, Austria), IL-10 and TNF-alpha by R&D system tests. All assays were performed twice: on diagnosis and 6 weeks thereafter. Results: GPX activity in study group was significantly higher before and during treatment than in control subjects (1.5-fold, p=0.02 and 2-fold, p=0.0007, respectively). MDA concentrations were higher in ALL group before treatment (1.4-fold, p=0.0001) and 6 weeks thereafter (1.2 fold, p=0.01) than in control group. SOD activity, TAS and vitamin E concentrations did not differ between the groups. IL-10 level was found to be significantly increased on ALL diagnosis, but not during therapy, when compared to control group (2-fold, p=0.02). TNF-alpha level was higher in patients before treatment then during treatment (3-fold, p=0.02) and as compare to the controls (2,5-fold, ns). IL-2 and IL-4 plasma concentrations were comparable in all groups in both time points. There was a correlation in children with ALL after 6 weeks therapy between MDA and IL-10 concentrations (r=0.59, p
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  • 4
    Publication Date: 2009-11-20
    Description: Abstract 4483 Introduction Reconstitution of immunity is considered as one of the most important factors predicting outcome after hematopoietic stem cell transplantation (HSCT). Age of the recipient as well as graft quality reflect on this process however this influence is not completely understood yet. In this study we aimed to evaluate the influence of graft quality on recovery of lymphocyte subpopulation. Patients and Methods The total number of 63 patients who underwent allogeneic transplantation in one center between May 2002 and November 2008, were included into the study. Median age of the patient was 8,6 (range 0.2-18) yrs. Patients were divided into 2 age groups: group 1 (n=26) children age 0,2-7 and group 2 (n=37) children 〉7 yrs. In all cases quality of graft were assessed by counting WBC, CD34 cells and CFU-GEMM. 45 patients (21 in group 1 and 24 in group 2) were available for evaluation of immune reconstitution: in those patients the absolute number of lymphocytes CD3/CD19 (B) cells, CD3/CD4 (T helper) cell, CD3/CD8 (T suppressor) cells and CD3/CD16+56 (NK) cells were measured 3 and 6 months after transplantation. Results Younger children (group 1) received higher median number of transplanted nucleated cells (4.9×108 vs 2.5×108, p=0.008), CD34 cells (5.6×106 vs 2.1×106, p=0.02) and CFU-GEMM (2.25×104 vs 1.17×104, p=0.01) than older ones (group 2). No differences were found in absolute values of B, T-helper, T-suppressor and NK cells at 3 and 6 months after transplantation (Table 1). In older children (group 2), but not in younger ones, the number of GFU-GEMM transplanted negatively correlated with number of T-suppressor cells 3 months post HSCT (p
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  • 5
    Publication Date: 2015-12-03
    Description: Introduction Current curative strategy for children after one or more relapses of AML or for those with primary refractory AML (ref/rel AML) should include allo-HSCT. There is no consensus regarding a choice of reinduction chemotherapy regimen to induce remission prior HSCT in these highly drug-resistant patients. It is important to prevent further toxicities especially associated with anthracyclines widely used in the front-line therapies. Pediatric phase II study demonstrated promising efficacy of TVTC, anthracycline-free protocol resulting in remission achievement and successful transfer to HSCT in 8 of 12 patients with pediatric ref/rel AML (Shukla N. et al. Pediatr Blood Cancer 2014;61:431-435). Further data concerning clinical effectiveness of this regimen are very limited. Patients and Methods A retrospective analysis of clinical outcomes was performed for 10 pediatric patients (aged 2.5-17 years, median 13 years) treated with TVTC protocol for ref/rel AML at Polish Pediatric Leukemia/Lymphoma Study Group institutions between February 2014 - May 2015. Eight patients had relapsed AML (first relapse n=5, second n=3), 2 had refractory disease. The protocol consisted of clofarabine 40mg/m2/day i.v. x 5 days, topotecan 1mg/m2/day i.v. continuous infusion x 5 days, vinorelbine 20mg/m2/week i.v. x 3, and thiotepa 15mg/m2/day i.v. x 1 day. Four patients received 2 cycles, and 6 patients one cycle of the regimen. Evaluation of results was based on the criteria presented in the trial report by Shukla N.et al. Results Two patients were not evaluable for response due to complications during the first TVTC cycle; one died of a sudden septic shock of undetermined etiology, another one developed a rapid respiratory failure in the course of invasive fungal infection and died two months later in persistent pancytopenia. Neither CR nor CRp were reported for the remaining cases. Two patients were subsequently eligible for HSCT. One patient treated for second AML relapse, demonstrated after one cycle of TVTC
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  • 6
    Publication Date: 2005-11-16
    Description: It was investigated whether in children demonstrating high risk of toxicity related to conventional preparative regimens (prep-reg) for allo-HSCT, the prep-reg based on Treosulfan (TREO) (Feit, Rastrup-Andersen, 1970) enables to avoid severe toxic complications without increased incidence of graft failure and/or relapse. From July 2000 to April 2005 the TREO-based prep-reg was used prior to allo-HSCT in 43 children with increased risk of severe Busulfan- and FTBI-based regimens related toxicity (RRT) and/or non-compliance. In 37 patients (pts) allo-HSCT was performed for, usually advanced, hematological malignancy, incl. 19 pts (1–17 yrs, med. 9) transplanted from MSD for ALL (n=8), AML (n=7), LCH (n=2), MDS (n=1) and NHL (n=1), and 18 pts (0.5–17 yrs, med. 9.5) from MUD for AML (n=7), ALL (n=4), CMML (n=3), NHL (n=2) and CML (n=2). Six pts (0.5–12 yrs, med. 6) underwent HSCT for congenital disorder, i.e. 5 from MSD for ALD (n=2), WAS (n=2) and B-DA (n=1), and one from MUD for osteopetrosis. Total of 24 pts were transplanted from MSD and 19 from MUD. TREO (3x10 g/m2, n=22; 3x12 g/m2, n=19; 3x14 g/m2, n=2) was given i.v. in various combination with FLUDA, CY, MEL or VP-16 acc. to diagnosis, risk factors of RRT and/or regimen used for previous HSCT. Prior MUD-HSCT and all pts with congenital disorders received ATG (n=18) or Campath (n=3). RRT was graded acc. to Bearman (1988). In 21 out of 43 pts (incl. all 6 with congenital diseases) no features of RRT occured, I° in 13, II° in 5, and III° in 4 (mucositis). Engraftment was achieved in all pts, except one transplanted from MUD for CML with low dose of CD34 cell (1.7x106/kg). Acute GvHD II–III° occurred in 9/24 pts after MSD-HSCT and in 10/19 after MUD-HSCT, chronic GvHD in 4/24 post MSD-HSCT and 1/19 after MUD-HSCT. Chimerism was evaluated in 22/24 pts after MSD-HSCT and in 18/19 post MUD-HSCT. Respectively, complete donor chimerism was observed in 17/22 and 16/18 pts, mixed in 5/22 and 1/18, and autologous recovery in 1/18 after MUD-HSCT. Non-relapse deaths occurred in 6 out of 37 pts with malignancy, incl. one 40 mo. post MSD-HSCT (pulmonary aspergillosis, cGvHD), and 5 after MUD-HSCT (abdominal aorta thrombosis day+59, LPD day+63, BKV infection day+66; intracranial bleeding day+138). The 1-year non-relapse mortality was 13,5%. Relapse was diagnosed in 8/19 pts post MSD-HSCT (4xAML, 4xALL) and in 1/18 after MUD-HSCT (sAML). Out of 24 pts transplanted from MSD, 15 are alive, i.e. 10/19 with malignant disease in CCR (med. 27, 16–50 mo.) and 5/5 with congenital disorder (med. 21, 6–58 mo.). After MUD-HSCT, 12/18 pts with malignancy are alive in CCR (med. 19, 7–42 mo.) and a child with osteopetrosis (4 mo.). At 3 years from HSCT in 19 pts with malignancy transplanted from MSD the progression-free survival (PFS) was 46% and overall survival (OS) 49%, while in 18 transplanted from MUD 82% and 68%. The PFS and OS estimated for 6 pts with congenital disorders at 4 years after HSCT was 67% and 100%. Conclusions: In children with high risk of conventional regimen related toxicity the prep-reg for allo-HSCT based on TREO given at the dose of 3 x 10–12 g/m2i.v. demonstrates almost exclusively mucosal toxicity, along with sufficient myeloablative and immunosuppressive effects. Its anti-leukemic effect is at least comparable with that one of Busulfan-based regimens.
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  • 7
    Publication Date: 2014-12-06
    Description: Background: Allogeneic stem cell transplantation (alloSCT) is a potential curative treatment for patients (pts) with myelodysplastic syndrome (MDS), with reported long-term survival of 27% to 54% depending on risk group. Myeloablative conditioning (MAC) considered as standard therapy is associated with substantial treatment related mortality (TRM), especially in older pts or those with therapy related disease (tMDS); on the other hand, high rate of relapse have been reported after reduced intensity conditioning (RIC). Therefore, Polish Adult Leukemia Group (PALG) in cooperation with Polish Pediatric Group for Hematopoietic Stem Cell Transplantation analyzed the outcome of MDS pts transplanted between 2000 and 2013 with respect to conditioning intensity. Material and methods. Three hundred and four pediatric and adult patients with median age of 38 years (range: 1-69) were retrospectively analyzed. The study cohort included pts with intermediate-2/high risk according to IPSS (136), unfavorable cytogenetics (86), secondary AML (43) and tMDS (35). Among adult pts (216), 74 (34%) were older than 50. The median time between diagnosis and transplant was 8 months (range:1-117). Before transplantation 202 pts had 10%. For conditioning, RIC protocols based on fludarabine were used in 180 pts and 102 pts were treated with myeloablative therapy based on busulphan. Stem cells from related (144) or unrelated (160) donors were grafted in median dose 4.75 (1.3-27.4)x106 of CD34+ cells/kg. Peripheral blood (PB) stem cells were transplanted in 222 pts. Thirty nine pts received allograft from HLA mismatched donors. Results: Engraftment occurred in 285 (94%) pts and 8 pts died before +21 day after transplantation. Infectious complications were observed in 252 (82%) pts during neutropenia (febrile of unknown origin 163, bacterial 53, fungal 24, bacterial and fungal 12). Late infections, assessed in those who survived 100 days, occurred in 130 (50%) pts, and were related mainly to CMV infection. Severe toxic complications (CTCAE grade 3-4) developed in 67 (22%) pts. Acute graft versus host disease (GVHD) grade 2-4 occurred in 77 (27%) pts, while chronic extensive GVHD in 37 (14.5%) pts. Forty seven pts experienced disease relapse after treatment. Over a median follow-up of 43 months (range: 15-70) 156 (51%) pts were alive. In 44 cases deaths were related to relapse, 36 pts died due to GVHD, 43 due to infection and 25 because of organ toxicity. Probability of 3-years overall survival (OS), disease free survival (DFS), relapse incidence (RI) and TRM were 0.51±0.03, 0.50±0.03, 0.18±0.03 and 0.47±0.03, respectively. OS (0.56±0.04 vs 0.44±0.04, p=0.036) and TRM (0.31±0.04 vs 0.43±0.04, p=0.040) were statistically better for pts transplanted after 2007 (Figure 1). In multivariate analysis the only factors associated with lower OS were bone marrow blasts before alloSCT 〉10% (p=0.05, HR 1.5), mismatched donor (p=0.015, HR 1.8), PB as source of stem cells (p=0.048, HR 1.5) and alloSCT performed after 2007 (p=0.029, HR 1.6). There were no statistically significant differences in OS, DFS, RI and TRM between pts conditioned with RIC or MAC when analyzed in whole study cohort or with respect to age group, IPSS risk group, cytogenetics, interval from diagnosis to alloSCT. Conclusions: Allogeneic SCT is an option for MDS patients in different age groups. Disease status at time of transplant, mismatched donor and PB source of stem cells, but not conditioning intensity are the most important determinant for the outcome. High rate of TRM remains a concern, despite improvement over time. Fig 1. Results of alloSCT in MDS Fig 1. Results of alloSCT in MDS Disclosures Jedrzejczak: Amgen, Novartis : Consultancy, Research Funding.
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  • 8
    Publication Date: 2018-11-29
    Description: Background Standard myeloablative conditioning treatment prior to allogeneic hematopoietic stem cell transplantation (alloHSCT) of children is associated with a considerable risk of severe adverse events (AEs). Previous clinical studies in adults confirmed that treosulfan-based conditioning has myeloablative, immunosuppressive and anti-neoplastic effects associated with favorable non-relapse mortality (NRM). Therefore, treosulfan-based conditioning treatment was prospectively evaluated in pediatric patients with hematological malignancies within an extended clinical phase II trial. Patients and Methods In this prospective, single-arm, open-label phase II trial we evaluated a treosulfan-based preparative regimen in pediatric patients with hematological malignancies undergoing alloHSCT. The trial was designed to assess safety and efficacy of a body surface area (BSA) adapted treosulfan dosing regimen of 10, 12 or 14 g/m2/day (according to individual BSA of ≤0.5, 〉0.5 to 1.0, or 〉1.0 m2) on Days -6 to -4. Objectives of the trial included overall survival (OS) based on Kaplan-Meier estimates, cumulative incidence (CI) of NRM and disease relapse/progression (RI). NRM was defined as the probability of dying after alloHSCT in the absence of persisting disease or previous occurrence of relapse/progression or graft failure. Moreover, the CI of acute/chronic graft versus host disease (a/cGvHD), the conditional CI of engraftment, Kaplan-Meier estimates of GvHD-free and Relapse/Progression-free Survival (GRFS) and cGvHD-free and Relapse/Progression-free Survival (CRFS), the incidence of complete donor type chimerism (defined as ≥ 95% donor cells), as well as frequencies of adverse events (AEs) until 100 days after alloHSCT were evaluated. Further, treosulfan concentration in plasma was analyzed to calculate AUC and Cmax in a subset of patients. Results Seventy pediatric patients with acute lymphoblastic leukemia (ALL [38.6%]), acute myeloid leukemia (AML, [41.4%]), myelodysplastic syndrome (MDS, [14.3%]), or juvenile myelomonocytic leukemia (JMML, [14.3%]) were enrolled between Nov-2014 and Apr-2016. The median patient age was 9.5 years (range 0-17 years) and median follow up was 12.0 months (range 11.5-17.7 months). Patients received treosulfan intravenously at a dose of 10 g/m2/day (8.6%), 12 g/m2/day (37.1%), or 14 g/m2/day (54.3%). Treosulfan was combined with fludarabine only (7.1%) or fludarabine and thiotepa (92.9%) at the investigators' discretion. The maximum conditional CI of granulocyte engraftment was 100.0% (90% CI: 97.7, 100.0). The incidence of complete donor-type chimerism at visit Day +28 was 94.2% (90% CI: 87.2, 98.0). OS at 12 months was 91.4% (90% CI: 83.9, 95.5). NRM at 12 months was only 1.4% (90% CI: 0.0, 3.8) and RI was 15.7% (90% CI: 8.6, 22.9). There was no statistical significant difference between the three dose groups with regard to any of these objectives. Grade II to IV and III to IV aGvHD were 26.1% and 8.7%, respectively. At 12 months overall cGvHD was 24.8% and moderate/severe cGvHD was 18.8%. GRFS at 12 months was 64.7% (90% CI: 54.2, 73.4) and CRFS was 66.0% (90% CI: 55.5, 74.6). The three most common CTCAE terms of at least grade III were mucositis oral (41.4%), infections and infestations - other (28.6%), and nausea (17.1%). One (1.4%) patient developed hepatic sinusoidal occlusion syndrome (grade II acc. to Jones) and recovered after 22 days. Frequencies of AEs with at least CTCAE grade III apparently correlated with increasing dose group. However, median AUC was comparable between the three different dose groups (1287 mg*hr/L [10g/ m2], 1268 mg*hr/L [12g/m2] and 1461mg*hr/L [14g/m2]) as evaluated in a subset of 58 patients. Median Cmax was also comparable between the different dose groups (628µg/mL [10g/m2], 583µg/mL [12g/m2] and 656µg/mL [14g/m2]). Conclusions The 12-month follow-up data of this phase II trial confirm that treosulfan-based conditioning with BSA-adapted dosing was safe and effective in pediatric patients with hematological malignancies. The cumulative incidence of OS and NRM compared favorably to those reported for other conditioning regimens. Treosulfan/fludarabin/thiotepa is therefore considered to be a reasonable alternative for myeloablative conditioning in this pediatric patient population. (Funded by medac GmbH, MC-FludT.17/M, EudraCT no: 2013-003604-39; ClinicalTrials.gov identifier: NCT02333058). Figure. Figure. Disclosures Kalwak: medac: Other: travel grants; Sanofi: Other: travel grants. Bader:Riemser: Research Funding; Medac: Patents & Royalties, Research Funding; Neovii: Research Funding; Cellgene: Consultancy; Novartis: Consultancy, Speakers Bureau. Gruhn:Jazz Pharmaceuticals: Honoraria. Patrick:medac: Other: Funding for EBMT conference fees and accomodation. Sykora:Aventis-Behring: Research Funding; medac: Research Funding. Corbacioglu:Gentium: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria. Locatelli:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy; Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kremens:DSMC for industry driven clinical study: Consultancy; Miltenyi Biotec Germany: Consultancy. Vora:Pfizer: Other: Advisory board; Medac: Other: Advisory board; Novartis: Other: Advisory board; Amgen: Other: Advisory board; Jazz: Other: Advisory board.
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  • 9
    Publication Date: 2011-11-18
    Description: Abstract 3109 The outcome of patients (pts) relapsing after stem cell transplantation (SCT) is poor with limited therapeutic approaches in this group. A second or subsequent SCT is an option, however both high treatment related mortality (TRM) and high rate of disease relapse have been reported after such procedure so far. The objective of the study was to determine efficacy and safety of allogeneic SCT in patients relapsing with lymphoproliferative diseases after prior alloSCT or autoSCT. Material and methods. Fifty pediatric and adult patients with Hodgkin lymphoma (HL-24), non-Hodgkin lymphoma (NHL-10), acute lymphoblastic leukemia (ALL-9) and multiple myeloma (MM-7) in median age 33.5 (range: 3–56) years were included into the study. Nine pts relapsed after previous alloSCT and 41 after autologous transplant. The median time interval between previous transplant and relapse and median time interval between transplants were 8 (range :1–45) and 19 (range: 3–89) months, respectively. Complete remission (CR) was achieved in 23 pts before current transplant, while remaining 27 pts undergone alloSCT with active disease. For conditioning, reduced intensity protocols based on fludarabine were used in 46 pts, 4 were treated with myeloblative therapy based on total body irradiation (TBI). Stem cells from sibling (27) or unrelated (23) donors were grafted in median dose 4.1 (1.5–12.4)x10e6 of CD34+ cells/kg. Results: Engraftment was observed in 44 (88%) pts, 6 pts died before +21 day after transplant. Severe toxic complication (CTCAE grade 3–4) developed in 13 (26%) pts with multiorgan failure (MOF) in 7 of them. Infectious complications were observed in 41 (82%) pts (febrile of unknown origin 25, bacterial 10, fungal 3, bacterial+fungal 3). Acute graft versus host disease (GVHD) 2–4 grade occurred in 19 (38%) pts, while chronic extensive GVHD in 10 (20%) pts. Fifteen (30%) patients relapsed after treatment. Over a median follow–up duration of 7 (range: 0–83) months, 19 (38%) pts were alive with median survival 25 (95%CI=14.5–35) months. Probability of 3-years overall survival (pOS) was 0.117±0.091. Among 31 (62%) pts who died, 11 early deaths (before +100 day post transplant) occurred: 4 due to infection and 7 because of MOF. Late deaths were caused by relapse (9), GVHD (7), toxicity (2) and infections (2). TRM was 44%. The only factor contributing to 3-year pOS was remission vs active disease before transplant (0.458±0.140 vs 0.085±0.073; p=0.006). CR before second transplant reduced 2.9-fold (95%CI=1.3–6.2, p=0.008) the risk of death after procedure. Other estimated factors for OS (age, type of first transplant, pts and donor gender, conditioning method, stem cell source, toxic and infectious complications, GVHD occurrence, interval time between relapse and second transplant and between transplants) by Kaplan-Meier method were not statistically significant. Patients with late relapse (〉6 months) after previous transplant reached survival plateau at 2 years (pOS=0.364±0.095 vs 0.0; ns). Conclusions: allogeneic SCT as a second procedure may be an option in relapsing patients with lymphoproliferative diseases after previous SCT. Remission status at time of salvage transplant is the most important determinant for the outcome. High rate of TRM remains a concern. Disclosures: No relevant conflicts of interest to declare.
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  • 10
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