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  • 1
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    Post-Transplantation Day +100 Minimal Residual Disease Detection Rather Than Mixed Chimerism Predicts Relapses after Allogeneic Stem Cell Transplantation for Intermediate-Risk Acute Myelogenous Leukemia Patients Undergoing Transplantation in Complete Remission
    Elsevier BV ; 2022
    In:  Transplantation and Cellular Therapy Vol. 28, No. 7 ( 2022-07), p. 374.e1-374.e9
    Details
    In: Transplantation and Cellular Therapy, Elsevier BV, Vol. 28, No. 7 ( 2022-07), p. 374.e1-374.e9
    Materialart: Online-Ressource
    ISSN: 2666-6367
    URL: Article
    DOI: 10.1016/j.jtct.2022.04.009
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2022
    ZDB Id: 3056525-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
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    Postallogeneic monitoring with molecular markers detected by pretransplant next‐generation or Sanger sequencing predicts clinical relapse in patients with myelodysplastic/myeloproliferative neoplasms
    Wiley ; 2014
    In:  European Journal of Haematology Vol. 92, No. 3 ( 2014-03), p. 189-194
    Details
    In: European Journal of Haematology, Wiley, Vol. 92, No. 3 ( 2014-03), p. 189-194
    Kurzfassung: Relapse is the major cause of treatment failure after allogeneic stem‐cell transplantation ( AHSCT ) for patients with myelodysplastic syndrome/myeloproliferative syndrome neoplasms ( MDS / MPN ). We evaluated the impact of molecular mutations on outcome and the value of molecular monitoring post‐transplantation. We screened 45 patients with chronic myelomonocytic leukemia ( n  = 39 patients, including seven with transformed‐acute myeloid leukemia), MDS / MPN unclassifiable ( n  = 5), and atypical BCR ‐ ABL 1 ‐negative CML ( n  = 1) for mutations in ASXL 1, CBL , NRAS , and TET 2 genes by molecular genetics including a sensitive next‐generation sequencing ( NGS ) technique. In 36 patients, sufficient DNA was available for molecular analyses. In particular, TET 2 and CBL mutations were screened applying amplicon deep sequencing. In 89% of cases, at least one mutation could be detected: ASXL 1 : n  = 18 (50%); CBL : n  = 7 (19%); TET 2: n  = 15 (42%); and NRAS : n  = 11 (32%). Survival after AHSCT at 5 yr was 46% (95% CI 28–64%) and was not influenced by any mutation. After a median of 6 months after AHSCT in 33% of the patients, one of the molecular markers was still detectable, resulting in a higher incidence of relapse than in patients with undetectable mutations (50% vs. 15%, P  = 0.04). In conclusion, pretransplant molecular mutation analysis can help to detect biomarkers in patients with MPN / MDS , which may be subsequently used as minimal residual disease markers after AHSCT .
    Materialart: Online-Ressource
    ISSN: 0902-4441 , 1600-0609
    URL: Issue
    URL: Article
    DOI: 10.1111/ejh.2014.92.issue-3
    DOI: 10.1111/ejh.12223
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2014
    ZDB Id: 2027114-1
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
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    Rituximab Plus Donor Lymphocyte Infusion (DLI) to Prevent or Treat Relapse for B Cell Malignancies after Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT)
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 4304-4304
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 4304-4304
    Kurzfassung: Dose-reduced conditioning followed by allogeneic stem cell transplantation (HSCT) is a potentially curative therapy in B non Hodgkin lymphomas (NHL). However, the number of patients who experienced an early relapse is significant, and the achievement of a prolonged second remission is usually a rare event. Posttransplant immunotherapy with DLI to induce graft versus lymphoma (GVL) effect is a reasonable option to prevent or treat relapse, however the risk of graft versus host disease (GvHD) is high. Since B-cells might serve as antigen presenting cells to induce GvHD, additional B-cell depleting therapy with monoclonal antibody (anti CD20) might reduce the risk of GvHD while inducing additional cytotoxicity to B-cells originating from B-cell lymphoma. In the current pilot study we investigated the feasibility of a combined rituximab (Rtx) plus DLI therapy in B-cell malignancies after allogeneic stem cell transplantation to prevent (n=10) or treat relapse (n=2). Twelve consecutive patients, 8 male and 4 female, affected by B cell malignancies and transplanted between July 2002 and February 2007, were included in this study. The median age at alloHSCT was 58 ys (range 27–64). The conditioning regimen consisted of melphalan (140 mg/m2), fludarabine (150 mg/m2) and ATG–Fresenius (30–60 mg/kg) (n=9) or busulfan (8–10 mg/kg), fludarabine (150 mg/kg) (n=3), donors were HLA identical sibling in the half of the group, with one HLA mismatched-unrelated donor. The source of stem cell was peripheral blood in all patients. Seven patients were not in disease remission at the time of HSCT. The indication of Rtx-DLI administration was prophylaxis of relapse in all but two patients. The schedule of this approach was: Rtx (375 mg/mq, in 4 consecutive weekly infusions), started at a median time of 194 dy from HSCT (range 77–895). DLI, in a single dose, was administered from a minimum of 1×105/Kg up to 5×106/Kg, after discontinuation of immuno-suppression, without signs of GvHD. Three patients developed acute GvHD after DLI, two with gastro-intestinal and one with cutaneous involvement, whereas 6/12 patients experienced chronic GvHD, limited in all but two. Two cases of bacterial and one case of Pneumocystis jirovecij pneumonia were diagnosed after the treatment, in 3 different patients. Two patients died in complete remission due to infectious complications. The median number of B-circulating lymphocytes before and after Rtx was 42/μL (range 0–477) and 4 (range 0–226) respectively, and the difference is not statistically significant in terms of incidence of infection in our group (χ2 test). After a median follow up of 21 mo (range 4–37) from the 1st Rtx infusion, 8/12 patients are alive at the last follow-up, six of them without disease, whereas 2 patients died due to progressive disease(table1). Rituximab and DLI post allogeneic HSCT seems to be a safe and effective approach to prevent early relapse in B malignancies in complete remission after allogeneic stem cell transplantation. Table 1 Pt no Indication of R-DLI Infection aGVHD cGVHD Relapse Last follow-up 1 prophylaxis pneumonia II (GI tract) n n alive in CR 2 prophylaxis n n n n alive in CR 3 prophylaxis n n n n alive in CR 4 prophylaxis n n n y alive with disease 5 prophylaxis n n lim n alive in CR 6 prophylaxis n n n n alive in CR 7 relapse n n lim y alive with disease 8 relapse n n n y dead with disease 9 prophylaxis PJP n ext n dead in CR 10 prophylaxis pneumonia n lim n dead in CR 11 prophylaxis n II (skin) lim y dead with disease 12 Prophylaxis N I (skin) ext n Alive in CR
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.4304.4304
    RVK:
    XA 33000
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2008
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
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    Outcome of HLA-Mismatched Unrelated Donor Allogeneic Stem Cell Transplantation Depends On the Intensity of the Conditioning Regimen.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 3393-3393
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3393-3393
    Kurzfassung: Abstract 3393 Poster Board III-281 Background: HLA-mismatched unrelated donors are increasingly becoming a graft source for both standard myeloablative (MAC) and reduced intensity conditioning (RIC) hematopoetic stem cell transplantation (HSCT). Patients and methods: We retrospectively analysed the effects of HLA-mismatching in 553 patients undergoing MAC (n = 342) or RIC (n = 211) unrelated donor HLA-matched (n = 289) or -mismatched (n = 264) HSCT with antithymocyte globulin as part of conditioning. Patient characteristics well matched between HLA-matched and –mismatched groups of MAC and RIC patients. Results: Median follow-up was 1946 days for MAC patients and 765 days for RIC patients. In MAC patients, there was no difference in the incidence of aGvHD, treatment related mortality (TRM) and overall survival (OS) between recipients of HLA-matched vs. –mismatched allografts. In RIC patients on the contrary, the incidence of aGvHD II-IV (46%, vs. 32.0% p = 0.05), III-IV (18%, % vs. 9.0 p = 0.07) and TRM (35% vs. 20%, p = 0.04) were higher and OS lower (31% vs. 50%, p = 0.001) for recipients of HLA-mismatched vs. –matched transplants. In the RIC patients, female donor gender (RR: 1.8; p = 0.02) and HLA-mismatch (RR: 1.8; p = 0.02) negatively influenced TRM while female donor gender (RR: 1.58, p = 0.03), HLA-mismatch (RR: 1.82, p = 0.003) and bad risk disease (RR: 2.14, p 〈 0.001) negatively impacted OS. Conclusion: Our analyses surprisingly reveal that the positive effect of ATG in HLA-mismatched transplants is only limited to patients undergoing standard myeloablative conditioning. HLA-mismatching and female donor gender negatively impact outcome of RIC allogeneic unrelated donor HSCT despite the use of ATG, highlighting the need for improved strategies. Acknowledgments We thank the staff of the BMT unit for providing outstanding care to our patients and the medical technicians for their excellent work in the BMT laboratory. Disclosures: Off Label Use: Antithymocyte globulin for prevention of severe GVHD.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.3393.3393
    RVK:
    XA 33000
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2009
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
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    Impact of Minimal Residual Disease after Allografting Detected By JAK2V617F, MPL or Calreticulin in Myelofibrosis Patients
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 4343-4343
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4343-4343
    Kurzfassung: Introduction: Residual minimal disease (MRD) in hematological malignancies has become a valid tool to predict clinical relapse after allogeneic stem cell transplantation (ASCT). Methods and Patients: We screened 154 patients with myelofibrosis who underwent ASCT for molecular residual disease by qPCR or next-generation sequencing (NGS) for JAK2V617F, MPLW515L and MPLW515K or Calreticulin (L367fs*46, and K385fs*47) mutations in peripheral blood (PB) on days +100 and +180 after transplantation. Out of 154 pts, 103 were JAK2V617F (n=101), 31 Calreticulin (CALR), and 4 MPL mutated, while 13 pts were triple negative. 136 pts could be followed after ASCT with one molecular marker. The median age of the pts was 58 years (range, 32-75 y). Patients had either primary myelofibrosis (n= 90), post ET/PV myelofibrosis (n=40), myelofibrosis in acceleration or were transformed to AML (n=6). Conditioning mainly relied on a busulfan-based reduced-intensity regimen. Donor were HLA-identical sibling (n=26), matched unrelated (n=71) or mismatched unrelated (n=39). JAK2V617F, MPL, and CALR mutations were measured by usage of Taqman PCR or in case of CALR Type 2 mutation by digital PCR on day +100 and day +180 from PB as described elsewhere. Results: After a median follow up of 78 months (range, 49-101 months) the 5-year estimated overall survival was 60% (95% CI: 50-70%) and the cumulative incidence of relapse at 5 years was 26% (95% CI: 18-34%) for the entire study population. On days +100 and +180 after transplantation in 27% and 12% of the patients the underlying mutation was still detectable in peripheral blood. The percentage of complete clearance was higher in CALR-mutated patients (96%) in comparison to MPL (75%) and JAKV2617F (70%) mutated pts. Whereas there was a trend for better survival for CALR-mutated patients in comparison to JAK2-mutated patients (71% vs 57%; p=0.48), once a patient achieved molecular remission post-transplant the risk of relapse remained low independently of the underlying mutation. Patients who were alive and without relapse at days +100 or +180 but with still detectable mutation in PB had a significantly higher risk of relapse than those who were molecular negative (62% vs 10%, p 〈 0.001; and 70% vs 10%, p 〈 0.001, respectively). In a multivariate analysis only high-risk disease status (HR 2.5; 95% CI: 1.18-5.25, p=0.016) and detectable MRD at day 180 (HR 8.36, 95% CI: 2.76-25.30, p 〈 0.001) were significant factors for a higher risk of relapse. Conclusions: JAK2V617F, CALR and MPL genetic lesions allow to monitor MRD in around 90% of the myelofibrosis patients after ASCT by qPCR or digital PCR in the PB. Persistence of MRD on days +100 or +180 in peripheral blood can be used to taper immunosuppressive drugs or to apply donor lymphocyte infusion to prevent clinical relapse. Disclosures No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.4343.4343
    RVK:
    XA 33000
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2015
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
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  • 6
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    Recovery of KIR Expression After Allogeneic Stem Cell Transplantation in Multiple Myeloma Patients
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 4555-4555
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4555-4555
    Kurzfassung: Abstract 4555 Introduction: Activating and inhibitory killer immunoglobulin like receptors (KIR) are predominantly expressed on natural killer (NK) cells. KIR mismatch allogeneic stem cell transplantation (alloSCT) has been reported to provide beneficial effects for Multiple Myeloma (MM). However, their recovery in MM patients remains poorly understood. We, therefore, analysed KIR recovery in 90 MM patients after alloSCT. Methods: KIR expression (CD158a/h, CD158b/b2, CD158e1/e2) on NK cells and T cell subsets was measured by flow cytometry at different time points after alloSCT. Results: During the first 90 days after alloSCT NK cells represent the largest lymphocyte subset. Activating receptors like NKp30 and NKp44 showed a fluctuating expression while members of the KIR family were expressed at a constant rate (20% of NK cells). There was no significant difference in the early post transplantation period (day 0–90) compared to later time points (day 360). In contrast, T cells showed increased KIR expression during the first 30 days after alloSCT, which was highly significant for CD158e (p=0,0001). After 30 days the expression declined to baseline. Furthermore, T cell activation marker HLA-DR reached its highest expression between days 60 and 90 when KIR receptors were expressed at their lowest level (27% vs. 8%, p 〈 0,0001). Conclusions: We conclude that KIR receptors were differentially expressed on NK and T cells. Because KIR receptors are constantly expressed by NK cells and NK cells are the most frequent lymphocyte populations early after alloSCT, NK cells may be useful for KIR mismatch cellular therapy. Disclosures: No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.4555.4555
    RVK:
    XA 33000
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2011
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
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    Disease-Specific Recovery of Regulatory T Cell After Allogenic Stem Cell Transplantation
    American Society of Hematology ; 2010
    In:  Blood Vol. 116, No. 21 ( 2010-11-19), p. 4689-4689
    Details
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 4689-4689
    Kurzfassung: Abstract 4689 Introduction: Allogenic stem cell transplantation (allo SCT) offers a potential curative approach for many malignant and non malignant haematological diseases. Despite its therapeutic benefit, long term immunodeficiency, poor immune reconstitution and Graft vs. Host Disease (GvHD) can often be limiting drawbacks. Since the nineties, regulatory T cell subsets (Treg) have been described and several lines of evidence indicated their implication on GvHD occurrence and progression. We analysed the immune reconstitution of 184 patients who underwent allo SCT at our Transplant Center from 2007 till 2009. Patients, Materials and Methods: Differential lymphocyte subsets were analysed by flow cytometry. Antigens were stained by usage of the following mAb: CD3, CD4, CD8, CD19, HLA-DR, CD56/CD16, CD45RA, CD45RO, CD45, γδ TCR, CD25, and CD127. Tregs were evaluated on simultaneous expression of CD4/CD25hi/CD127low. Data were obtained in monthly intervals for the first six months and thereafter every six months for the next 3 years. Data were analysed for three different subgroups: Multiple Myeloma (MM: n=83), Myelofibrosis (PMF: n=22) and AML/MDS (n=51). Smaller number subgroups of patients with CML (n=11), NHL (n=10) and ALL (n=7) were included into the overall analysis but not evaluated separately. Results: The mean value of Treg cell number before allo SCT was 2,5% of the total leukocyte number in all patients. There was no significant difference in the Treg level in any of the three major groups (MM: 2,2%; PMF: 2,1% and AML/MDS: 2,03%). All patients exhibited a significant reduced number of Treg cells during the first 30 days after allo SCT (MM: 0,79%; p= 0,009; PMF: 0,41%; p= 0,01; MDS/AML: 0,6%; p=0,01). Between day 30 and 60 after allo SCT patients with MM had a transient Treg recovery to baseline level (2,4%) while Tregs of patients with PMF or MDS/AML remained significantly lower in comparison to baseline value (PMF: 0,72%, p=0,002 and MDS/AML 0,81%, p=0,01 respectively). One year after allo SCT a faster Treg recovery (1,3% and 1,8% respectively) was observed in MM and MDS/AML patients while patients with PMF still maintained a significant reduction (0,65%; p=0,01). Interestingly, in the second year after allo SCT, Treg cell levels were decreased in all investigated subgroups (MM: 1,1%, p=0,008; PMF: 0,7%, p=0,02 and MDS/AML: 0,7%, p 〈 0,0001), while after 3 years Treg cell number achieved pretransplant level. In contrast to Treg cells, total T cells are only transiently but significantly reduced within the first 180 days. Conclusion: A highly dynamic Treg cell recovery after allo SCT was observed in our group of patients. Even one year after allo SCT Treg reconstitution is still ongoing. Our data highlight that there is a distinctive difference in Treg recovery among the various fore mentioned diseases. Treg reconstitution appeared to be prolonged in patients with PMF in comparison to the other subgroups. Our data provide a basis for further analysis towards differential Treg reconstitution and its potential impact on allo SCT complications. Disclosures: No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V116.21.4689.4689
    RVK:
    XA 33000
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2010
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
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  • 8
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    Induction Chemotherapy Followed Immediately by Busulfan-Based Reduced Conditioning and Allografting in Elderly Patients with Advanced MDS or sAML.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 3387-3387
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3387-3387
    Kurzfassung: Abstract 3387 Poster Board III-275 〈 〉 Introduction: Allogeneic stem cell transplantation after a dose-reduced conditioning has become a reasonable treatment option for elderly patients with MDS/sAML. For patients with high number of blasts prior transplantation, the risk of relapse is considerably. To reduce the risk of relapse after dose-reduced allograft we performed a study using an anthracycline based induction chemotherapy (amsacrine, cytosine-arabinoside, fludarabine) followed immediately by a reduced intensity conditioning therapy consisting of busulfan (8mg/kg). Patients and Methods: Between November 2005 and November 2008, 49 patients with MDS (n = 24), CMML (n = 8) and sAML (n = 17) and a median age of 61 years (r: 26 – 73) and a median number of 13% blasts were included. Stem cell source were unrelated (n = 43) or related donor (n = 6). Results: No graft failure was observed and the median time to leukocyte engraftment ( 〉 1.0 × 109 /l) was only 10 days (r: 7 – 32). The incidence of acute graft-versus-host disease grade II to IV was 39 % and of grade III / IV was 14 %. Chronic GvHD was noted in 57 % of the patients, which was limited in 35 % and extensive in 32 % of the patients. After a median follow-up of 15 months (r: 3 – 35) the two-years estimated disease-free and overall survival was 49 % (95 % CI 33 – 65 %) and 54 % (95 % CI 39 – 69 %), respectively. The 1 year cumulative incidence of treatment-related mortality was 29 % (95 % CI 15 – 43 %). The 2 year cumulative incidence of relapse was 18 % (95 % CI 6 – 30 %). Patients with fully matched related or unrelated donor had a better survival than patients transplanted from mismatched donor (69 % vs. 37 %; p=0.06). Conclusions: A sequential approach using anthracycline based induction chemotherapy followed immediately by a busulfan based reduced conditioning regimen and allogeneic stem cell transplantation from related and unrelated donors resulted in a fast engraftment and a relative low risk of relapse in elderly patients with advanced MDS or sAML. To lower the therapy related mortality a careful donor selection is mandatory. Disclosures: No relevant conflicts of interest to declare.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.3387.3387
    RVK:
    XA 33000
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2009
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
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    Lenalidomide Maintenance Therapy After Toxicity-Reduced Myeloablative Allograft As Salvage Therapy for Efractory/Relapsed Myeloma Patients
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 3024-3024
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 3024-3024
    Kurzfassung: Abstract 3024FN2 Reduced-intensity conditioning (RIC) regimen followed by allogeneic stem cell transplantation (SCT) has become a reasonable treatment option for patients with multiple myeloma who are refractory or have relapse to an autograft. However, in comparison to standard myeloablative conditioning RIC resulted in higher risk of relapse. Maintenance therapy after autologous transplantation has shown to improve survival while after allogeneic SCT data are lacking so far. We here report the results of myeloablative toxicity-reduced allograft consisting of intravenous busulfan (12.2 mg/kg) and cyclophosphamide (120 mg/kg) followed by lenalidomide maintenance in 33 patients with multiple myeloma who relapsed to an autograft. A total of 32 patients had received one (n=16), two (n=15), or even three (n=1) autografts, and 1 patient was refractory to 2 induction therapies and failed to collect autologous stem cells. The median duration of remission after the autograft was 12 months. The primary endpoint of the study was non-relapse mortality at 1 year and secondary objectives were evaluation of response, incidence of acute and chronic graft-versus-host disease as well as progression and overall survival. To prevent graft-versus-host disease antithymocyte globulin (ATG Fresenius®) was given at a median dose of 20 mg/kg on day -3, -2, and -1. Lenalidomide was started earliest at day 120 after transplantation if there were no signs of infection or graft-versus-host disease. The median time between last autograft and allogeneic transplantation was 20 months. 19 patients were treated with fully HLA-matched unrelated donor, 8 patients had a mismatch donor, and 6 patients were transplanted from an HLA-identical sibling. 2 patients died of treatment-related complications resulting in a cumulative incidence of non-relapse mortality at 1 year of 6% (95% CI: 0–14%). After transplantation 27% developed grade II graft-versus-host disease, and severe grade III graft-versus-host disease was seen in 6% of the patients. Complete remission was noted in 46% of the patients, partial remission was seen in 48% and stable disease in 3%. The median interval between allogeneic transplant and start of lenalidomide was 168 days. The median starting dose was 5 mg (range 5–15 mg) without dexamethasone for 21 day followed by 1 week rest. 9 patients did not receive lenalidomide maintenance due to ongoing graft-versus-host disease, cytopenia or patient's wish. The median number of lenalidomide cycles was 6 (range 1–30). During follow-up 13 patients discontinued lenalidomide treatment due to progressive disease (n=6), GvHD (n=3), thrombocytopenia (n=2), or fatigue (n=2). In 10 patients lenalidomide dose could be increased to 10 or 15 mg, respectively. The major toxicities of lenalidomide were acute graft-versus-host disease grade I – III (21%), viral reactivation (12%), thrombocytopenia grade III-IV (12%), neutropenia grade III-IV (6%), peripheral neuropathy grade I-II (12%), or other infectious complications (6%). During follow-up 9 patients experienced relapse resulting in a cumulative incidence of relapse at 3 years of 42% (95% CI: 18–66%). The 3 year estimated probability of progression-free and overall survival was 52 % (95% CI: 28–76%) and 79 % (95% CI: 63–95%), respectively. In the current trial neither the deletion 13q14 nor the use of mismatch donor nor the chemosensitivity prior allogeneic SCT could be identified as risk factor for survival. This study showed that toxicity-reduced myeloablative conditioning regimen is feasible and highly effective in relapsed patients with multiple myeloma resulting in an acceptable treatment-related mortality. Lenalidomide as maintenance therapy is feasible early after transplantation but toxicity especially the induction of graft-versus-host disease should be considered. Disclosures: Kröger: Celgene: Research Funding. Kropff:Janssen-Cilag: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.3024.3024
    RVK:
    XA 33000
    RVK:
    XA 10000
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2011
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
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    Anti-thymocyte globulin overcomes the negative impact of HLA mismatching in transplantation from unrelated donors
    Elsevier BV ; 2008
    In:  Experimental Hematology Vol. 36, No. 8 ( 2008-08), p. 1047-1054
    Details
    In: Experimental Hematology, Elsevier BV, Vol. 36, No. 8 ( 2008-08), p. 1047-1054
    Materialart: Online-Ressource
    ISSN: 0301-472X
    URL: Article
    DOI: 10.1016/j.exphem.2008.03.011
    RVK:
    XA 42470
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2008
    ZDB Id: 2005403-8
    Standort Signatur Einschränkungen Verfügbarkeit
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