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  • 1
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5900-5900
    Abstract: Introduction: Bendamustine is a bifunctional alkylating agent with low toxicity that produces both single- and double-strand breaks in DNA, and shows only partial cross resistance with other alkylating drugs. Treatment of patients with newly diagnosed multiple myeloma using Bendamustine and Prednisone in comparison to Melphalan and Prednisone results in superior complete response rate and prolonged time to treatment failure (Poenisch et al, Res Clin Oncol 132: 205-212;2006). So far, however, reliable information on stem cell toxicity and mobilization of stem cells for autologous stem cell transplantation (SCT) after induction treatment with a combination of bendamustine, prednisone and bortezomib (BPV) is missing. Material and Methods: A retrospective analysis of peripheral blood stem cell mobilization and autologous SCT was performed in 35 patients with multiple myeloma who had received at least two cycles of a BPV induction therapy consisting of bendamustine 60 mg/m2 on days 1 and 2, bortezomib 1.3 mg/m² on days 1, 4, 8 and 11, and prednisone 100 mg on days 1, 2, 4, 8 and 11 between October 2008 and May 2014. The mobilization regimen consisted of cyclophosphamide 4 g/m2 and G-CSF (2x5µg/kg). Apheresis was started as soon as peripheral blood CD34+ counts exceeded 20x106/l with a harvest target of 8x106 CD34+/kg. The minimal accepted target was 2x106 CD34+/kg. Results: A median number of two (range 1–5) BPV treatment cycles were given to the patients. The majority of the patients (n = 31, 89 %) responded including 2 sCR, 5 nCR, 11 VGPR, and 13 PR. Three patients had MR, and 1 SD. Stem cell mobilization and harvest was successful in all patients. In 19 of 35 patients (54 %) a single apheresis was sufficient to reach the target. The median number of aphereses was one (range 1-4) and the median CD34+ cell-count/kg was 13.5 (range 3.2-33.1) x106. All patients received an autologous SCT. The pre-transplantation conditioning therapy consisted of melphalan 200 mg/m2. In 8 patients with concomitant heart amyloidosis or severe renal insufficiency melphalan dose was reduced to 100 or 140 mg/m2. Engraftment was successful in 34 of 35 patients. The median time to leucocytes count 〉 l×109/l was reached after 11 (range 9–18) days and the time to untransfused platelet count of 〉 50×109/l was 13 (range 10–55) days. 34 patients (97%) responded after the autologous SCT with 11 sCR, 2 CR, 7 nCR, 7 VGPR, and 7 PR. The progression free survival at 18 months was 87 % and overall survival was 92 %. Conclusion: Stem cell mobilization and autologous SCT is feasible in multiple myeloma patients who have received BPV induction therapy. Disclosures Al-Ali: Novartis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Lange:Novartis: Consultancy, Honoraria, 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: 2014
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  • 2
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 2573-2573
    Abstract: Characterisation of antigen expression patterns is part of the standard diagnostic work-up in acute myeloid leukemia (AML). But the biological & clinical implication of such antigen expression patterns have not been studied extensively & remain unclear in AML patients (pts) undergoing allogeneic stem cell transplantation (SCT). We analyzed the diagnostic antigen expression patterns of 162 AML pts (median age 64.7 years [y, range 46.6-76.2y]) with available data who received allogeneic peripheral blood SCT after non-myeloablative conditioning (NMA-SCT) between 2001 & 2013 at our institution. Conditioning regimen was fludarabine 3x30mg/m2 & 2Gy total body irradiation. Donors were human leukocyte antigen (HLA) matched related (12%) or HLA matched (59%) or mismatched unrelated (29%). Mutation (mut) status of the NPM1, CEBPA, IDH1, IDH2 & DNMT3A gene, presence of FLT3 -ITD & FLT3-TKD & the expression status of BAALC, ERG, MN1, EVI1, miR-9 & miR-181a at diagnosis were accessed. Pts were grouped according to the European LeukemiaNet (ELN) genetic classification in 22% favorable (fav), 24% intermediate-I (int-I), 21% intermediate-II (int-II) & 32% adverse (adv). Median follow up was 3.2y. To assess antigen expression patterns at diagnosis for all pts, flow cytometric analysis utilizing a standard panel (CD2, CD7, CD11b, CD13, CD14, CD15, CD33, CD34, CD38, CD45, CD56, CD61, CD64, CD65, CD117 & Glycophorin A) of mononuclear cells in bone marrow (BM) was performed. Using R's gplot package we performed unsupervised hierarchical clustering of the antigen expression which revealed 4 subgroups with distinct antigen expression patterns (Figure 1). At diagnosis, pts grouped in cluster 1 (n=19) had higher white blood count (WBC, P=.004) & lower peripheral blood (PB) blast count (P =.03) & were more likely to have de novo AML (P =.05). They were also less likely to have trisomy 8 (P=.08) by trend & more likely to have normal karyotype (KT, P=.05), to have ELN fav risk (P =.04), to be NPM1 mut (P =.002) & to be DNMT3A mut by trend (P=.08) & had lower miR-181a (P=.04), lower BAALC (P 〈 .001), lower ERG (P=.01) & lower MN1 expression (P 〈 .001). Pts grouped in cluster 2 (n=35) had higher WBC (P 〈 .001), PB blasts (P 〈 .001) & BM blasts (P=.005) at diagnosis. They were less likely to have trisomy 8 (P=.008) & to have deletion (del) 7/7q (P =.07) by trend, were more likely to be NPM1 mut (P =.002) & to have FLT3 -ITD (P 〈 .001) & had lower BAALC (P =.1) & lower EVI1 expression (P =.09) by trend. Pts grouped in cluster 3 (n=59) had lower WBC (P 〈 .001), PB blasts (P 〈 .001) & BM blasts (P 〈 .001) at diagnosis & were less likely to have de novo AML (P 〈 .001). They were more likely to have trisomy 8 (P=.05), del5/5q (P=.004), monosomal KT (P=.04), complex KT (P=.07) by trend & ELN adv risk (P=.04), were less likely to be NPM1 mut (P =.03) & FLT3 -ITD by trend (P=.08) & had lower ERG (P=.008) & higher miR-9 (P=.009) expression. Pts grouped in cluster 4 (n=49) had lower WBC (P=.03), higher PB blasts (P=.007) & BM blasts (P 〈 .001) at diagnosis. They were less likely to have del5/5q (P=.008) & NPM1 mut (P 〈 .001) & had lower miR-9 (P=.007) & higher BAALC (P 〈 .001), ERG (P 〈 .001) & MN1 (P 〈 .001) expression. For the entire set of pts, belonging to one of the antigen expression clusters did not impact on outcome. However, when the ELN groups were regarded separately, within the ELN fav group, cluster 1 pts had a significantly shorter event free survival (EFS, P=.04, Figure 2A) & within the ELN int-I group, cluster 3 pts had a trend for better (P=.096) & cluster 4 pts for worse EFS (P=.087). In conclusion, the antigen expression patterns at diagnosis obtained by unsupervised cluster analysis associated with distinct biological & clinical features (Figure 2B): NPM1 mut were enriched in clusters 1 & 2. Cluster 1 was characterized by ELN fav risk, normal KT, de novo disease & lower BAALC, ERG, MN1 & miR-181a expression. Cluster 2 was characterized by a high incidence of FLT3-ITD. We found more pts with ELN adv risk, monosomal KT, secondary AML & low miR-9 expression in cluster 3 & higher miR-9 as well as lower BAALC, ERG & MN1 expression levels in cluster 4. Even though we did not observe a prognostic impact of the antigen expression patterns in the entire cohort, the patterns may help to refine the ELN risk classification for AML pts undergoing SCT. Assessing the diagnostic antigen expression patterns provides information on disease biology, clinical parameters and potentially disease aggressiveness in AML. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Franke: BMS: Honoraria; MSD: Other: Travel Costs; Novartis: Other: Travel Costs. Niederwieser:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 3
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 5439-5439
    Abstract: Introduction: Up to 30% of patients (pts) undergoing stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) with or without prior chemotherapy mobilize poorly. Plerixafor is a potent CXCR4 receptor antagonist that is licensed for stem cell mobilization in autologous stem cell donors with multiple myeloma (MM) or lymphoma, who show poor mobilization after stimulation with recombinant G-CSF (r-metHuG-CSF, Filgastrim). Here we present our experience with plerixafor in poorly mobilizing autologous donors. Patients and Methods: We performed 35 stem cell collections between January 2011 and December 2014 in 28 poorly mobilizing autologous donors with MM (n=14), non-Hodgkin lymphoma (NHL, n=11), Hodgkin lymphoma (n=1) or both MM & NHL (n=2), adding plerixafor to the stimulation regimen with recombinant G-CSF. Known risk factors for poor mobilization included: diagnosis of lymphoma (50%); older age (61% 〉 60y at apheresis); 〉 1 chemotherapy lines (86%) & pretreatment with melphalan (18%). Median age of patients (pts) was 61 years (y, range 37-72y) at stem cell collection and 15 of the 28 pts were females. All pts received previous treatment with G-CSF (2x5µg/kg body weight [BW]) followed by a large volume leukapheresis (maximal 4 x total blood volume). All pts received 0.24 mg/kg BW plerixafor following insufficient mobilization of CD34+ cells into the peripheral blood (PB, 〈 10/µl CD34+ cells) - either after peripheral reconstitution of white blood cells (WBC, 〉 1 Gpt/l) following chemotherapy (n=22, 79%) or after 5 days of stimulation with G-CSF in steady state (n=6, 21%). Six pts treated with chemotherapy prior to mobilization received a second dose of plerixafor in response to insufficient CD34+ cell harvesting on the first collection day. As a control cohort, we evaluated the data of 151 collections from MM, NHL or Hodgkin lymphoma pts (106 males, 45 females, median age 56y, range 22-74y) with efficient mobilization in response to G-CSF treatment over the same time period. Results: The median concentration of CD34+ cells in PB before & after the first application of plerixafor was 8.4/µl (range 2.9-20.5 /µl) & 23.1/µl (range 10.2-54.1 /µl) respectively, corresponding to a median 3.3-fold increase (range 1.4-5.3-fold, P 〈 0.001, Figure 1). In comparison, pts in the control group had a median concentration of 101.9/µl (range 13-1190/µl) CD34+ cells in PB on the day of stem cell collection (Figure 1). The median CD34+ cell yield for pts receiving plerixafor was 3.7x10^6/kg BW (range 1.6-12.8x10^6/kg BW) compared to 10.5x10^6/kg BW (range 2.1-38.8x10^6/kg BW) in the control cohort (Figure 2). As expected, the WBC count in the product was higher in the plerixafor group (median 899.9x10^8, range 446-2214x10^8) compared to the efficiently mobilizing control cohort (median 470.2x10^8, range 99.9 -1537.1x10^8, P 〈 0.001). The vitality of the cells after thawing was tested with methan blue staining & was comparable in both groups: median 85.3% (range 73.3-92.8%) in the plerixafor group & 84.4% (range 50.6-96.8%) in the control cohort (P=0.242). Furthermore, all harvests were tested for their proliferation capacity by quantifying colony forming units (CFU). Pts receiving plerixafor had a median CFU number of 22.5 (range 1-199), which did not differ from the control cohort with a median of 200.2 CFUs (range 1-1341, P=0.568). To date, 22 (78.6%) of the poorly mobilizing pts have received an autologous stem cell transplantation. All showed good peripheral WBC (median day 11, range 10-15) & platelet (median day 16, range 11-46) recovery. Discussion: Our data shows that addition of plerixafor can increase the efficacy of stem cell harvesting in poor mobilizers. The collected stem cells fulfilled the appropriate quality control criteria including vitality after thawing ( 〉 50%) & proliferation capacity. We identified a median 3.3-fold increase in CD34+ cell concentration in PB & a median CD34+ cell yield of 3.7x10^6/kg BW after the application of plerixafor in poor mobilizers. Despite the fact that the CD34+ cell yield in pts receiving plerixafor remained significantly lower than the control cohort, we were able to harvest 〉 2x10^6/kg BW CD34+ cells in 93% (n=26) of poor mobilizers. Thus, the mobilization outcome of pts receiving plerixafor is acceptable and within the expected range. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Franke: BMS: Honoraria; MSD: Other: Travel Costs; Novartis: Other: Travel Costs. Niederwieser:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 4
    In: Bone Marrow Transplantation, Springer Science and Business Media LLC, Vol. 57, No. 5 ( 2022-05), p. 824-826
    Type of Medium: Online Resource
    ISSN: 0268-3369 , 1476-5365
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2004030-1
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  • 5
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 3065-3065
    Abstract: Abstract 3065 Allogeneic hematopoietic cell transplantation (HCT) following reduced-intensity-conditioning (RIC) is a curative therapeutic option in elderly patients with AML. Yet, hematological relapse (HR) and non-relapse mortality (NRM) remain major issues. The impact of AML characteristics, post-induction consolidation chemotherapy (PCC) in patients with complete remission (CR), type of donor [unrelated (UD) vs. related (RD)], graft cell count, and Donor-cell-chimerism (DCC) on long-term outcome and management of relapse after HCT following 200 cGy TBI + fludarabine 30 mg/m2 for 3 days followed by mycophenolate mofetil and cyclosporine were analysed in 245 consecutive patients with AML [132 male/113 female; median age 62 years] transplanted at the University of Leipzig. De novo and secondary AML were diagnosed in 151 (62%) and 94 (38%) patients respectively. A positive leukemic CD34-phenotype 〉 15% was present in 60%.Cytogenetics were high and intermediate (IR)-risk in 64 (26.7%) and 166 (69%) patients respectively. FLT3 -mutations (FLT3 mut) were present in 32 (28%) of the 115 patients with known FLT3 status. CR at HCT was present in 85% (CR1, n=155; CR2, n=53). The number of PCC applied was 0 in 88 (42%), 1 in 93 (45%), and 2 in 25 (12%). Donors were UD in 197 (80%) and RD in 48 (20%) patients. DCC in flow-sorted CD34+-marrow cells at days 28, 56, 84, and at 3 months interval thereafter was monitored by PCR of polymorphic micro satellite regions. After a median follow-up of 3.6 years, survival (OS), leukemia-free-survival (DFS), NRM, and Relapse (RI) at 5-years were 39%, 34%, 32% and 51% respectively. Engraftment was 95.5%. Incidence of acute GvHD 〉 grade 3, limited and chronic GvHD was 22.5%, 20%, and 44.6% respectively. In multivariate analysis, type of AML, cytogenetics, CD34+-phenotype, and graft cell counts (CD3+, CD34+- and natural killer-cells) had no impact on outcome. Irrespective of the number of PCC applied, outcome was similar for CR1 and CR2. For the entire cohort and also for patients with IR-cytogenetics in CR, FLT3 mut did not adversely affect OS or RI. The lower RI after UD-HCT (39%) compared to RD-HCT (63%) (p=0.04) was opposed by a higher NRM after UD-HCT (36%) vs. 13% for RD-HCT (p=0.05) so that long-term OS and LFS were similar for both donor types. Chronic GvHD was associated with a superior OS, LFS and lower RI compared to patients without GvHD or with acute GvHD only (p 〈 0.0005). Irrespective of leukemic CD34+-phenotype, CD34+-DCC day28 〈 90% was highly predictive of inferior OS (12%) and higher RI (95%) vs. OS of 50% and RI of 39% if CD34+-DCC day28 was 〉 90% (p 〈 0.0001). In multivariate analysis, UD (p=0.007), female donor/male patient (p=0.02), and a higher CD34+- (p=0.01) but not CD3+-cells in the graft correlated with CD34+-DCC day28 was 〉 90%. HR and CD34+-DCC 〈 90% without HR were managed by immunomodulation + chemotherapy. Overall, CR was achieved in 29% of HR and 36.4% of CD34+-DCC 〈 90%. Relapse beyond day 100, a declining CD34+-DCC rather than a HR, and induction of GvHD correlated with a superior response and OS after relapse. Donor cells rather than the usual AML prognostic features predict long-term survival and relapse after RIC-HCT. In particular, CD34+-DCC is very effective in predicting outcome and identifying patients at risk of relapse thereby allowing early immunomodulation to enhance the graft-versus-leukemia effect. Yet, research is needed to further optimize the graft-versus-leukemia effect without the injurious effects of GvHD. Disclosures: No relevant conflicts of interest to declare.
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    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 6
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 5033-5033
    Abstract: Introduction: Relapse of the malignant disease remains the major challenge after reduced intensity conditioning (RIC) HCT. Here we investigate the outcome of haematological relapse after low dose TBI-based conditioning regimens and the possibility to monitor minimal residual disease in patients with AML with the aim to prevent haematological relapse. Patients and methods: From 7/98 – 12/06, 156 consecutive pts [86 m/70 f; median age 61 (range 21–75) y] with CD34+ AML, n=138 and high-risk MDS, n=18 received RIC-HCT. Stage of disease at HCT was CR1, n= 99 (63%), CR2, n=18 (12%), and 〉 CR2, n=39 (25%). HCT were performed from matched related donors (n=40) or matched unrelated donors (n=116) after 200cGy TBI ± fludarabine 30 mg/m2/day on 3 days followed by mycophenolate mofetil and cyclosporine. Chimerism was monitored at days (d) 28, 56, 84, and at 3 months interval thereafter in unsorted as well as flow-sorted CD3+ and CD34+ bone marrow cells by FISH for the XY chromosome in gender mismatched (100–300 IP) or PCR based analysis of polymorphic micro satellite regions in gender matched HCT. A decrease of 〉 5% CD34+ donor chimerism (“CD34+ relapse”) was followed by a taper of immunosuppression. Haematological relapse was defined as increase of blasts to 〉 5%. Results: Of the 156 patients, 141 pts engrafted as shown by donor T-cell chimerism. OS, RI, and NRM at 5 y were 38±0,05%, 47±0,06%, and 30±0,05% respectively. From the 141 patients, 48 had hematological relapse. Treatment of relapse included reduction of immunosuppression, low dose AraC and intensive chemotherapy ± mobilized buffy coat. CR was achieved in 50% of the patients. Reduction of immunosuppression and/or DLI (p=0,04), amount of overall donor chimerism at diagnosis (p=0,01), the interval from HCT to relapse (p=0,02), and the occurrence of GvHD (p=0,05) were factors associated with CR in the multivariate analysis. Survival of patients with haematological relapse, however, was poor (3,6±0.03% at 5a). All patients with haematological relapse within 100 d died despite therapy. Survival was independently influenced by the time of relapse after HCT ( 〈 100 d vs. 〉 100 d; p=0.001), by the myeloblast count in the marrow (p=0.01) and by the type of relapse (haematological vs. “CD34 relapse” only). All patients with haematological relapse and available CD34+ donor chimerism (38/48 patients) had a decrease of CD34+ chimerism a median of 17 (range 0–181) d before the diagnosis of haematological relapse. Decrease of CD34+ chimerism without total chimerism decrease was observed in 12 additional patients (8,7%) a median of 149 (range 56–852) d after HCT. CD34+ donor chimerism amounted 84 (0–92)% before and returned to 100 (93–100)% after reduction of immunosuppression. Survival of these patients was 90±9% at 4 y. Conclusions: We conclude that relapse after low-dose TBI based conditioning has a poor outcome with survival of 〈 10% at 5 years in patients with AML. All patients with haematological relapse within 100 days died despite therapy. Determination of CD34+ donor chimerism allows early detection of relapse in patients with AML and can be used to tailor the immunosuppressive therapy after HCT.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 7
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 141, No. 11 ( 2015-11), p. 2013-2022
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
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    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
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  • 8
    In: American Journal of Hematology, Wiley, Vol. 92, No. 4 ( 2017-04), p. 388-396
    Abstract: In acute myeloid leukemia (AML), leukemia‐initiating cells exist within the CD34+/CD38− cell compartment. They are assumed to be more resistant to chemotherapy, enriched in minimal residual disease cell populations, and responsible for relapse. Here we evaluated clinical and biological associations and the prognostic impact of a high diagnostic CD34+/CD38− cell burden in 169 AML patients receiving an allogeneic stem cell transplantation in complete remission. Here, the therapeutic approach is mainly based on immunological graft‐versus‐leukemia effects. Percentage of bone marrow CD34+/CD38− cell burden at diagnosis was measured using flow cytometry and was highly variable (median 0.5%, range 0%–89% of all mononuclear cells). A high CD34+/CD38− cell burden at diagnosis associated with worse genetic risk and secondary AML. Patients with a high CD34+/CD38− cell burden had shorter relapse‐free and overall survival which may be mediated by residual leukemia‐initiating cells in the CD34+/CD38− cell population, escaping the graft‐versus‐leukemia effect after allogeneic transplantation. Evaluating the CD34+/CD38− cell burden at diagnosis may help to identify patients at high risk of relapse after allogeneic transplantation. Further studies to understand leukemia‐initiating cell biology and develop targeting therapies to improve outcomes of AML patients are needed.
    Type of Medium: Online Resource
    ISSN: 0361-8609 , 1096-8652
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 1492749-4
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  • 9
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 5945-5945
    Abstract: Introduction: Prognosis of patients (pts) with high risk acute lymphatic leukemia (ALL) in first complete remission (CR) or ALL 〉 CR1 is poor. For years, myeloablative conditioning followed by allogeneic stem cell transplantation (HCT) was the only curative treatment option for eligible pts. Over the past years, reduced intensity conditioning (RIC) regimens have been introduced to provide a curative treatment for elderly pts or ones with comorbidities ineligible for myeloablative chemotherapy. In this retrospective survey we analyzed the outcomes of ALL pts not eligible for conventional myeloablative HCT who were treated with RIC-HCT. Patients and Methods: Twenty-eight (55% male, 45% female) consecutive pts, who underwent RIC-HCT from sibling (MRD) or unrelated donors (MUD) between 2003 and 2013 in our institution were analyzed. The median age at transplantation was 58 (range 23 to 71) years. The conditioning regimen consisted of Fludarabine 30 mg/m2 from days -4 to -2 and a 200 cGy total body irradiation on days -1 or 0 before HCT. Reasons for RIC HCT as opposite to myeloablative chemotherapy was age over 50 years for MUD, and age over 55 years for MRD HCT. Eight (28.5%) pts were younger than 50 years and had comorbidities, making them ineligible for a myeloablative conditioning regimen. Median follow up was 2.4 years for pts alive. Three pts (10.7%) underwent second HCT, one after early transplant failure and two after late rejections. Six HCTs (19.4%) were performed from sibling donors, 17 (54.8%) from human leukocyte antigen (HLA) matched unrelated donors and eight (25.8%) from HLA mismatched ( 〉 1 allele) donors. Eight of our patients (28.5%) were Philadelphia chromosome (Ph) positive. Results: After two years the overall survival (OS) was 49±10% and event-free survival (EFS) was 40.5±9.4% with a non-relapse mortality incidence of 34±9.6%. The cumulative incidence of relapse (CIR) amounted 37±9.6% at two years. There was no statistically significant difference in two years OS in pts after RIC-MRD vs RIC-MUD, however CIR was higher in pts with MRD than in pts with MUD, though without reaching statistical significance. Patients in CR1 had higher two years OS 63.1+12.1 compared to patients in CR2 or worse 42.4+14.8 though without reaching statistical significance. Noteworthy, six of eight patients in the high-risk Ph+ cohort are still alive and only one of them relapsed after HCT. Of the three pts who underwent second HCT, one died due to Graft versus Host Disease (GvHD) eight months after the second transplantation. The other pts are still in persistent CR seven and two years after the second HCT. Conclusion: RIC-HCT can be used in pts with ALL and is certainly a curative option for pts with higher age (up to 71 years) or severe comorbidities. In the high-risk Ph+ cohort we observed remission rates of 62.5%. Prospective studies are needed to define the role of RIC-HCT in high risk ALL or in remission after relapse even if only an one antigen mismatch unrelated donor is available. Disclosures Jaekel: Novartis: Honoraria. Al-Ali:Novartis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Niederwieser:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gentium: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
    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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  • 10
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 55, No. 6 ( 2014-06), p. 1274-1280
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2014
    detail.hit.zdb_id: 2030637-4
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