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  • 1
    In: Chemotherapy Research and Practice, Hindawi Limited, Vol. 2012 ( 2012-04-10), p. 1-7
    Abstract: Purpose . Bone loss is a common phenomenon following allogeneic haematopoietic stem cell transplantation (allo-HSCT). The study aimed on tolerance and efficacy of zoledronic acid (ZA) in patients after allo-HSCT. Methods. 40 patients’ with osteoporosis or osteopenia were recruited on this phase II study. ZA was given at a dose of 4 mg IV every 3 months for 2 years (yrs). BMD was determined by dual-energy X-ray absorptiometry (LS lumbar spine, FH femur hip). Patients were evaluated for deoxypyridinoline (Dpd) and calcium excretion by longitudinal measurements. Results . 36 patients who had received at least 3 doses of ZA were evaluable. 26 patients had at least two BMD measurements since baseline (BMD group). Among these patients, BMD increased from 0.97 ± 0.15 to 1.10 ± 0.18  g/cm² (LS baseline—2 yrs, Δ + 11.6 ± 6.0 %, P 〈 0.001 ) and from 0.82 ± 0.10 to 0.91 ± 0.10  g/cm ² (FH baseline—2 yrs, Δ + 7.5 ± 7.0 %, P 〈 0.001 ). Factors associated with an increase in BMD were younger age, female donor sex, and immunosuppression with CSA/MTX. Conclusion . ZA was generally well tolerated; it increases BMD and reduces Dpd excretion significantly in patients with bone loss after allo-HSCT.
    Type of Medium: Online Resource
    ISSN: 2090-2107 , 2090-2115
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 26 ( 2013-09-10), p. 3259-3271
    Abstract: To evaluate the role of a second allogeneic hematopoietic stem-cell transplantation (HSCT2) given for relapsed acute leukemia (AL) after related or unrelated first hematopoietic stem-cell transplantation (HSCT1) and to analyze the role of donor change for HSCT2 in both settings. Patients and Methods We performed a retrospective registry study on 179 HSCT2s given for relapse after HSCT1 from matched related donors (n = 75) or unrelated donors (n = 104), using identical or alternative donors for HSCT2. Separate analyses were performed according to donor at HSCT1. Results Independent of donor, 74% of patients achieved complete remission after HSCT2, and half of these patients experienced relapse again. Overall survival (OS) at 2 years was 25% ± 4% (39% ± 7% after related HSCT2; 19% ± 4% after unrelated HSCT2). Long-term survivors were observed even after two unrelated HSCT2s. Multivariate analysis for OS from HSCT2 confirmed established risk factors (remission duration after HSCT1: hazard ratio [HR], 2.37; 95% CI, 1.61 to 3.46; P 〈 .001; stage at HSCT2: HR, 0.53; 95% CI, 0.34 to 0.83; P = .006). Outcome of HSCT2 was better after related HSCT1 than after unrelated HSCT1 (2-year OS: 37% ± 6% v 16% ± 4%, respectively; HR, 0.68; 95% CI, 0.47 to 0.98; P = .042, multivariate Cox regression). After both related and unrelated HSCT1, selecting a new donor for HSCT2 did not result in a relevant improvement in OS compared with HSCT2 from the original donor; however, donor change was not detrimental either. Conclusion After relapse from allogeneic HSCT1, HSCT2 can induce 2-year OS in approximately 25% of patients. Unrelated HSCT2 is feasible after related and unrelated HSCT1. Donor change for HSCT2 is a valid option. However, a clear advantage in terms of OS could not be demonstrated.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Herbert Publications PVT LTD ; 2012
    In:  journal of Anesthesiology and Clinical Science Vol. 1, No. 1 ( 2012), p. 7-
    In: journal of Anesthesiology and Clinical Science, Herbert Publications PVT LTD, Vol. 1, No. 1 ( 2012), p. 7-
    Type of Medium: Online Resource
    ISSN: 2049-9752
    Language: English
    Publisher: Herbert Publications PVT LTD
    Publication Date: 2012
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  • 4
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4540-4540
    Abstract: Abstract 4540 Microangiopathy (MA) and graft-versus-host disease (GvHD) are serious complication after allogeneic hematopoietic cell transplantation (HCT). MA is comparable to a slight form of thrombotic thrombocytopenic purpura (TTP), characterized as de novo thrombocytopenia, hemolysis, evidence of fragmentocytes in the blood, hypertension, cerebral confusion and uremic syndrome. Conglomerates of platelets and uncleaved multimere of vWillebrand-Factor (vWf)) are the pathophysiological correlate and result in multiple occlusions of microvessels. Up to now the exact pathomechanism for chronic GvHD (cGvHD) is unknown but oftenly associated with decreasing platelets counts. In patients (pts) with cGvHD we previously described an increased number of vWf +and CD34+ microvessels and of CD8+ T-cells in the bone marrow (Hill,W Blood 112 abstract No 1166, 2008). The aim of this study is to screen bone marrow biopsies of pts after HCT for histological changes of vascular quality regarding to MA and correlate these findings with the development of cGvHD. Bone marrow biopsies of 36 pts (25 male, 11 female, 45 years median, range 18–64) after HCT (day 105 to 4623) were screened for overall number of vWf+ vessels, the number of sinus with a thick wall of vWf + deposit with a size 〉 15 × 8μ (plaquesinus) and the number of vWf+ deposit without evidence of sinus (plaques) as well as the number of megakaryocytes between Oct 2001 and Jul 2006. Morphological findings were correlated with GvHD or non-GvHD and with MA by the well known grading (aMA) at the time of acute GvHD (aGvHD) and with as a modificated grading (cMA) at the time of simultaneous cGvHD. Results: 26 of 36 pts had cGvHD (6 with limited and 20 with extensive disease). 22 had aGvHD before and 4 did not. 8 of the 36 pts had neither aGvHD nor cGvHD, 2 pts suffered from aGvHD. Regarding to aMA a moderate grade was found in 14 pts, a mild form was detected in 15 pts, and 7 pts did not have any signs of aMA. The levels of maximal elevation of lactatdehydrogenase (LDH) and maximal decrease of platelets (each p value 〈 0,02) were as followed: absent grade LDH mean 248 U/L and platelets decrease mean 36 %; mild grade LDH 299 U/L and platelets 52 % and moderate grade LDH 505 U/L and platelets 70%. Additional parameters (each p 〈 0,01) were evidence of fragmentocytes, increase of retikulocytes, anemia, minimal aPTT and minimal fibrinogen. 20 of 36 pts had aGvHD stage II-IV. 14 of these had moderate grade of aMA (5 mild, 1 absent). Otherwise none of 16 pts without aGvHD had moderate aMA (p=0,000). 10 had mild and 6 absent aMA. Additionally 14 of the 26 pts with cGvHD had a moderate grade of aMA before in contrast to none of the 10 pts with or without aGvHD (p=0,003). The grading of MA at the time of cGvHD based of minimal platelets count and maximal LDH elevation (cMA) as followed: for grade absent platelets 163 G/L and LDH 219 U/L, for mild platelets 98 G/L and LDH 331 U/L and for moderate platelets 38 G/L and LDH 344 U/L. Additional parameters were platelet decrease, anemia, elevation of reticulocytes as well as level of vWf in serum (169, 308 respectively 480%) (p 〈 0,04).11 of 26 pts with cGvHD had a moderate grade cMA vs none of 10 pts without cGvHD (p=0,013). The cumulative level of Ciclosporin A in serum was higher in mild and moderate grade of cMA vs absent (13,3 vs 7,3g p=0,036). The duration were 190 vs 88 days (p=0,06). The numbers of vWf+ vessels, of plaqesinus and plaques were higher in pts with cGvHD than non-cGvHD (16 vs 7/mm2 p=0,000, 3,4 vs 0,7/mm2, p=0,000, respectively 1,2 vs 0,3/mm2 p=0,054). cMA mild and moderate grade had more vWf+ vessels, plaquesinus and plaques than absent grade (each p 〈 0,022). A change into severe grade of MA was prevented by discontinuation of immunosuppression and infusions of fresh frozen plasma (3 pts) as well as of IVIG for suspected ITP. Conclusion: Low grade MA was more often observed than expected from the literature. MA can be demonstrated morphologically by vWf+ deposits in endothelial-cells in bone marrow and can be graded also at the time of cGvHD. The high frequency of moderate grade at the time after engraftment with or without aGvHD is remarkable for development of a cGvHD with prognostic, pathogenetic and therapeutic relevance. From clinical, laboratory and morphological point of view microangiopathy seems to be part of aGvH reaction, followed by deposits of vWf+ material in the bone marrow, consumption of platelets by fixation to uncleaved multimere of vWf with the consequence of thrombocytopenia. Disclosures: Hill: Novartis: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 5
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 2105-2105
    Abstract: on behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Background The use of an unmanipulated graft is increasingly adopted in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) from haploidentical family donors. Methods This survey aimed to assess the outcome of adult patients with de novo acute leukemia (AL) who were reported to the EBMT registry, and who received an unmanipulated peripheral blood (PB) and/or bone marrow (BM) graft from a haploidentical family donor between 2007 and 2011. 106 patients with consolidated follow-up and fully audited data were selected for the purpose of this analysis. Results The median folllow-up was 36.2 months (range, 1.3-66.1). 74 pts received a haplo-SCT for acute myeloid leukemia (AML, 70%), 31 pts for acute lymphoblastic leukemia (ALL, 28%) and 1 pt for acute biphenotypic leukemia (1%). The haplo-SCT was the first allogeneic transplant for all the patients. However, 17 pts had previously received an autologous SCT (16%). 26 pts were transplanted in CR1 (24%), 27 pts in CR2 or higher CR (26%) and 53 pts in more advanced disease (50%). The number of HLA mismatches was 2 in 16 pts (15%), 3 in 14 pts (13%), 4 in 27 pts (26%) and 5 in 44 pts (46%). Median age at time of haplo-SCT was 46 years (range, 18-66). 81 pts out of 106 received a reduced-intensity conditioning regimen (RIC, 76%). 92 pts received anti-thymocyte globulins (87%) as part of the conditioning regimen and 5 pts received alemtuzumab (4.7%). Stem cell source was bone marrow (BM) for 37 pts (35%) and peripheral blood (PB) for 69 pts (65%). Median dose of infused CD34+ cells was 2x10e6/kg (range, 0.85-5.3) for BM and 8x10e6/kg (1.72-13,19) for PB. Donor median age was 38 years (range, 19-71). 26 male pts received a graft from a female donor (24%). CMV donor/host serostatus was as follow: neg/neg for 13 pts (12%), pos/neg for 9 pts (9%), neg/pos for 25 pts (24%) and pos/pos for 57 pts (55%), missing for 2 pts. Finally, the Karnofsky Performance Status (KPS) at time of haplo-SCT was 〉 80% for 74 pts (71%), 〈 or = 80% for 30 pts (29%) and missing for 2 pts. 98 out of 106 pts engrafted (96.1%), with a median time for reaching ANC 〉 0.5x10e9/L of 17.5 days (range, 11-63). The cumulative incidence of grade II or higher acute GvHD was 30±4%. The 2-years incidence of chronic GvHD was 39±5% (n=41: 23 limited, 18 extensive). At 3 years, the estimates of leukemia-free survival (LFS) for pts transplanted in CR1, CR2 or in advanced disease were 54±10%, 37±9%, 12±5%, respectively. The estimates of overall survival (OS) were 67±10%, 48±10% and 11±5%, respectively. The cumulative incidences of relapse (RI) were 37±10%, 26±9% and 59±7%, respectively. Non-relapse mortality (NRM) incidences were 8±6%, 37±9% and 29±6%. In a multivariate analysis including all relevant factors for LFS, disease status at transplant was found to be significant (HR=2.89; 95%CI:1.73-4.83; p=0.0001) in conjunction with the number of HLA mismatches 〉 3 (HR=1.69; 95%CI: 1-2.86; p=0.05). Disease status and number of HLA mismatches ( 〉 3) were also significant risk factors for OS: (HR=3.79; 95%CI:2.24-6.39; p 〈 10-3) and (HR=1.87; 95%CI: 1.06-3.30; p=0.03,), respectively. For RI, 2 factors were identified: disease status (HR=3.94; 95%CI: 2.10-7.39; p 〈 10-3) and patient age (≥35y) (HR=2.57; 95%CI: 1.13-5.85; p=0.02). Finally, the number of HLA mismatches ( 〉 3) was the only significant parameter associated with NRM (HR=3.06; 95%CI: 1.05-8.93; p=0.04). Conclusion These data suggest that unmanipulated graft haplo-SCT is a valid treatment option in acute leukemia. We are currently completing this EBMT survey to include all patients reported to the registry ( 〉 350 patients). The current LFS and NRM rates support the use of such transplant approach as part of the treatment algorithms for adult acute leukemia patients with an indication to allogeneic SCT but lacking an HLA-identical sibling or matched-unrelated donor. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 6
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2573-2573
    Abstract: Background: Allogeneic stem cell transplantation (SCT) can provide long-term disease control in selected patients with relapsed refractory NHL. Restricted availability of a matched sibling donor limits its use especially for patients with rapidly progressing disease in whom unrelated donor search cannot be awaited and in patients from ethnic minorities. Donor sources such as haplo-identical relatives or cord blood represent reasonable alternatives but data of alternative donor transplants in lymphoma is sparse. We therefore intended to compare outcome after transplants performed with sibling or fully matched unrelated donors with alternative sources such as cord blood and haplo-identical donors. Methods: Information of patients with mantle cell lymphoma (MCL), DLBCL, T-cell lymphoma (TCL) and follicular lymphoma (FL) who received an SCT from a sibling donor (SIB), 10/10 matched unrelated donor (MUD), haplo-identical donor (HAPLO) or cord blood (CORD) between 2007 and 2012 was downloaded from the EBMT database. Comparisons of outcome after transplants from different donors were performed with regard to overall survival (OS), non relapse mortality (NRM), relapse (REL) and acute GVHD incidence. For comparisons between donors SIB has been chosen as the reference group. Results: 2798 patients with NHL were identified in the EBMT database meeting the inclusion criteria. 2065 received a transplant from a SIB, 447 from a MUD, 167 from CORD (18 MCL, 36 DLBCL, 43 FL, 70 TCL) and 119 from a HAPLO donor (16 MCL, 30 DLBCL, 22 FL, 51 TCL). 66% were male and 34% female patients. Median age at transplant was 49 years (range: 18-72). 24% (n=684) had DLBCL, 27% (n=755) FL, 17% (n=464) MCL and 32% (n=895) TCL. 56% received their transplant in CR, 17% in PR and 27% had active disease at SCT. Active disease was more common in the HAPLO group (p 〈 0.01). Karnofsky index (KI) was 80% or higher in 71% of patients. KI below 80% was also more common in the HAPLO group (p=0.02). Other variables were balanced. Median follow-up after SCT was 27 month (CI 25 to 29). OS of patients who received an alloSCT from a SIB or MUD was not significantly different, whereas OS of HAPLO and CORD transplants was significantly worse than SIB transplants (HR 1.9 CI 1.5 -2.5, HR 1.8 CI 1.4 -2.2, p 〈 0.0001, Figure 1). Worse OS after alternative donor transplant (reference SIB) was observed across all studied disease entities. Relapse incidence after conventional transplants (SIB, MUD) and alternative donor transplants (HAPLO, CORD) was not significantly different within the whole group (HAPLO: HR 1.2 95% CI 0.9-1.8 p= 0.23; CORD: HR 1.1 95% CI 0.7-1.4, p=0.74; Figure 1) and across all studied disease entities. In contrast, whereas NRM incidence was not significantly different between SIB and MUD, it was, but significantly higher with alternative donor transplants (HAPLO: HR 1.8 95% CI 1.3-1.8, p 〈 0.001; CORD: HR 1.9 95% CI 1.5-2.5, p 〈 0.001). With the exception of FL where MUD in addition to HAPLO and CORD transplants had a significantly higher NRM incidence than SIB transplants, NRM incidence was generally higher in alternative donor transplants than in MUD and SIB. Most interestingly, acute GVHD incidence was significantly increased in MUD compared to SIB (p=0.003) transplants but not in HAPLO (p=0.08) or CORD (p=0.34) transplants. Multivariate adjustment for diagnosis (MCL, DLBCL, FL, TCL), remission prior to SCT, KI (KI 〈 80% vs. 〉 80%) and conditioning intensity (RIC vs. MAC) confirmed worse OS for HAPLO (HR 1.5 CI 1.2-2.0, p=0.003) and CORD (HR 1.6 CI 1.3-2.0, p 〈 0.00001). Multivariate modeling of relapse incidence and adjustment for the above mentioned covariates revealed no different relapse incidences between donor groups. However, NRM incidence was significantly higher in MUD (reference SIB, HR 1.4 CI 1.1–1.8, p=0.015) and CORD (reference SIB, HR 2.5 CI 1.7–3.6, p=0.015) but not in HAPLO transplants (reference SIB, HR 1.2 CI 0.7–2.2, p=0.53). Conclusions: Alternative donor transplants are a valuable option if no suitable SIB or MUD donor is available. With the limited number of patients studied here, relapse incidence after alternative donor transplants was not significantly different from conventional transplants. Higher NRM incidence in alternative donor transplants might be improved with increasing refinement of the procedure, such as post-transplant cyclophosphamide approaches. Figure 1) Outcome (OS, Rel, NRM) after alloSCT with different donors Figure 1). Outcome (OS, Rel, NRM) after alloSCT with different donors Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 7
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2590-2590
    Abstract: Background: Relapse of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is frequently treated with 2nd allo-HSCT. Donor change has not yielded a significantly different outcome over choosing the original HLA-identical donor (Christopeit et al., JCO 2013). Using a haploidentical donor at second allo-HSCT might represent a feasible option (Tischer et al., BMT 2014) Study design and population: To define the role for second haploidentical allo-HSCT for AL relapsing after 1st allo-HSCT, a retrospective analysis was conducted 63 consecutive patients (female n=30, male n=33; AML n=51, ALL n=12) from 9 German centers were included. Median age was 40 years (range, 16-65). Grafts at 1st allo-HSCT were from matched related (32%), matched unrelated (33%), mismatch unrelated (18%), haploidentical donors (6%), and other donors, including cord blood (8%). Median duration of complete remission (CR) after 1st allo-HSCT was 414 days (range, 18-1633). Relapse was initially treated by cytoreductive chemotherapy in all cases; stage at start of conditioning for haploidentical second allo-HSCT was CR in 27%, active disease in 66% and not evaluated in 8%. Conditioning for second HSCT was myeloablative/reduced in 14%/86% To overcome the HLA barrier, 23 patients (36%) received ex vivo T-cell depletion (TCD), following either CD3/CD19 negative or CD34 positive selection. 4 patients received in vivo TCD only, two received no TCD at all, and 35 patients (55%) received high-dose cyclophosphamide post-transplant according to the Baltimore protocol. Results: Neutrophil engraftment was achieved after a median of 12 days (range, 8-26). 50 patients (78%) achieved CR after 2nd haploidentical allo-HSCT, out of which 23 (46%) relapsed again. After a median follow-up of 425 days, 47 patents had died, 22 from leukemia, and 25 from treatment-related causes. Kaplan-Meier estimated overall survival at one and two years from haploidentical second HSCT was 41+/-6% and 19+/-6%. Conclusions: Haploidentical second allo-HSCT is a promising approach to the treatment of AL relapse after first allogeneic transplant. OS rates at least comparable to alternative treatments were observed. Different strategies to overcome the HLA barrier seem feasible. This retrospective study was registered as NCT01997918 at clinicaltrials.gov. Maximilian Christopeit and Johanna Tischer as well as Wolfgang Bethge and Christoph Schmid contributed equally to this work. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 8
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5842-5842
    Abstract: Background: HLA haploidentical stem cell transplantation with T-replete grafts and post-transplant immunosuppression with high-dose cyclophosphamide after reduced intensity conditioning has evolved into an increasingly accepted method of alternative donor transplantations in adults. Reported transplantation related mortality, GVHD and relapse rates are at least comparable to those of HLA matched donor transplantations. Purpose: To assess the feasibility of this approach in children as a first or second allogeneic transplantation after myeloablative or reduced toxicity conditioning. Patients/methods: Ten consecutive transplantations in children with either malignant (n=6) or non-malignant diseases (n=4) at a single institution transplanted with unmanipulated bone marrow from parental HLA haploidentical donors were analyzed. In the malignant cohort (3 ALL, 2 AML, 1 MDS) four patients were in advanced disease status (2 NR, 2 CR3) and three had received a prior allogeneic transplantation (2 relapses, 1 rejection). Conditioning in these patients was either TBI-VP16 (n=3) or myeloablative treosulfan-based (n=3). Among the non-malignant patients (2 IL10R deficiency, 1 sickle cell disease, 1 XIAP), one had rejected a prior T-cell depleted HLA haploidentical transplantation. These patients were conditioned with alemtuzumab, treosulfan, fludarabine ± thiotepa. All patients in both groups received cyclophosphamide 14,5mg/kg on days -3 and -2. GVHD prophylaxis consisted of cyclophosphamide 50mg/kg on days +3 and +4, tacrolimus and MMF from day +5. In the absence of GvHD MMF was stopped on day +35, tacrolimus tapered from day +60 (malignant) or day+100 (non-malignant). Results: After a median follow-up of 6 months (1-25), 9 of 10 patients are fully engrafted, alive and free of disease. One patient with AML not in remission at transplantation died from pulmonary hemorrhage on day +24. He was also treated for CMV viremia pre-existing before transplantation. One ADV reactivation requiring pre-emptive treatment and no invasive fungal infections were noted in the other patients. Engraftment was recorded at a median of 17 days (neutrophils) and 26 days (platelets). Only in one patient transient acute skin GVHD (overall grade II) was observed, while no patient developed chronic GVHD. Mean CD3 counts of 310/µl, 937/µl and 1868/µl, CD4 115/µl, 291/µl and 1010/µl, CD8 176/µl, 589/µl and 802/µl and CD19 102/µl, 360/µl and 641/µl were measured on days +100, +180 and +365 respectively. Conclusion: HLA haploidentical transplantation with post-transplant cyclophosphamide appears to be a safe and promising approach with very low GVHD rates and excellent immune reconstitution in children with malignant as well as non-malignant diseases. This may be combined with myeloablative as well as reduced toxicity conditioning regimes and is a promising approach even as a second allogeneic procedure after relapse or rejection following a first allogeneic transplant. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 9
    In: Blood, American Society of Hematology, Vol. 115, No. 14 ( 2010-04-08), p. 2960-2970
    Abstract: Posttransplantation lymphoproliferative disease (PTLD) associated with Epstein-Barr virus (EBV) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. PTLD is efficiently prevented by adoptive transfer of EBV-specific T cells from the donor. To make EBV-specific T cells available in urgent clinical situations, we developed a rapid protocol for their isolation by overnight stimulation of donor blood cells with peptides derived from 11 EBV antigens, interferon-γ surface capture, and immunomagnetic separation. Six patients with PTLD received 1 transfusion of EBV-specific T cells. No response was seen in 3 patients who had late-stage disease with multiorgan dysfunction at the time of T-cell transfer. In 3 patients who received T cells at an earlier stage of disease, we observed complete and stable remission of PTLD. Two patients have remained free from EBV-associated disease for more than 2 years. CD8+ T cells specific for EBV early antigens rapidly expanded after T-cell transfer, temporarily constituted greater than 20% of all peripheral blood lymphocytes, and were maintained throughout the observation period. Thus, a rapid and sustained reconstitution of a protective EBV-specific T-cell memory occurred after the infusion of small numbers of directly isolated EBV-specific T cells.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 10
    In: Journal of Immunotherapy, Ovid Technologies (Wolters Kluwer Health), Vol. 33, No. 5 ( 2010-06), p. 523-537
    Type of Medium: Online Resource
    ISSN: 1524-9557
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2010
    detail.hit.zdb_id: 2048797-6
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