S Giebel

Publications (24)77.33 Total impact

• Article: Intermediate-dose Ara-C plus G-CSF for stem cell mobilization in patients with lymphoid malignancies, including predicted poor mobilizers.

  S Giebel, T Kruzel, T Czerw, M Sadus-Wojciechowska, J Najda, E Chmielowska, S Grosicki, A Jurczyszyn, M Pasiarski, E Nowara, M Glowala-Kosinka, A Chwieduk, I Mitrus, A Smagur, J Holowiecki
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  ABSTRACT: The optimal protocol for mobilization of hematopoietic stem cells in patients with lymphoid malignancies has not been determined so far. We retrospectively analyzed the efficacy and safety of Ara-C at a dose of 1.6 g/m(2) compared with CY at a dose of 4.0 g/m(2), both combined with filgrastim. Seventy and forty-five patients, respectively, were included, among whom 60% were defined as 'predicted poor mobilizers'. The use of Ara-C was associated with significantly higher peak number of circulating CD34(+) cells compared with CY (P<0.0001). In the Ara-C group, 95% of patients with multiple myeloma (MM) collected at least 5 × 10(6) CD34(+) cells/kg required for tandem transplantation, and 97% of lymphoma patients collected at least 2 × 10(6) CD34(+) cells/kg, needed for a single autologous hematopoietic SCT (autoHSCT), which was achieved with a single leukapheresis in 91% of cases. Results for the CY group were significantly inferior (P<0.0001). No patient mobilized with Ara-C experienced febrile neutropenia, whereas 35% required platelet transfusions. Among patients who proceeded to autoHSCT, the time of both neutrophil and platelet recovery was significantly shorter for those mobilized with Ara-C than CY. We conclude that intermediate-dose Ara-C+filgrastim is a very effective and relatively safe mobilization protocol for patients with lymphoid malignancies.Bone Marrow Transplantation advance online publication, 7 January 2013; doi:10.1038/bmt.2012.269.
  Bone marrow transplantation 01/2013; · 3.00 Impact Factor
• Article: Impact of different dimethyl sulphoxide concentrations on cell recovery, viability and clonogenic potential of cryopreserved peripheral blood hematopoietic stem and progenitor cells.

  A Smagur, I Mitrus, S Giebel, M Sadus-Wojciechowska, J Najda, T Kruzel, T Czerw, J Gliwinska, M Prokop, M Glowala-Kosinska, A Chwieduk, J Holowiecki
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  ABSTRACT: Background and Objectives  The procedure of autologous hematopoietic stem/progenitor cell transplantation requires cryopreservation. Addition of DMSO is necessary to secure the viability of such cells, but this solvent is potentially toxic to stem cells' recipient. 10% DMSO solution is used by the majority of transplant centres. The aim of our study was to test if DMSO concentration might be reduced without negative impact on cell recovery and clonogenicity. Materials and Methods  Samples were prospectively collected from 20 patients. Small volumes of leukapheresis products were frozen with different cryoprotective mixtures, containing 10%, 7·5%, 5% and 2·5% DMSO, respectively. The quality of cryoprotective mixtures was evaluated based on recovery, viability and clonogenic potential of hematopoietic stem cells after defreezing. Results  Reduction in DMSO concentration to 7·5% or lower was associated with decreased recovery of nucleated cells. In contrast, the number of colonies was highest for 7·5% DMSO with significant differences when compared to 10% DMSO solution. Conclusion  Reduction in DMSO concentration from 10% to 7·5% may have favourable impact on hematopoietic recovery after autologous transplantation. The findings require confirmation in a clinical setting.
  Vox Sanguinis 10/2012; · 2.86 Impact Factor
• Article: Allogeneic hematopoietic SCT in patients with AML following treosulfan/fludarabine conditioning.

  J Casper, J Holowiecki, R Trenschel, H Wandt, K Schaefer-Eckart, T Ruutu, L Volin, H Einsele, G Stuhler, L Uharek, [......], A R Zander, K Larsson, M Markiewicz, S Giebel, T Kruzel, H A Mylius, J Baumgart, U Pichlmeier, M Freund, D W Beelen
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  ABSTRACT: An alternative reduced-toxicity conditioning regimen for allogeneic transplantation, based on treosulfan and fludarabine, has recently been identified. The safety and efficacy of this new conditioning regimen has been investigated prospectively in patients with AML. A total number of 75 patients with AML in CR were treated with 3 × 14 g/m(2) treosulfan and 5 × 30 mg/m(2) fludarabine, followed by matched sibling or unrelated SCT. Patients were evaluated for engraftment, adverse events, GVHD, and for non-relapse mortality, relapse incidence, overall and disease-free survival (DFS). All patients showed primary engraftment of neutrophils after a median of 20 days. Non-hematological adverse events grade III-IV in severity included mainly infections (59%) and gastrointestinal symptoms (7%). Acute GVHD grade II-IV occurred in 21% and extensive chronic GVHD occurred in 16% of the patients. After a median follow-up of 715 days, the 2-year overall and DFS estimates were 61% and 55%, respectively. The 2-year incidences of relapse and non-relapse mortality reached 34% and 11%, respectively. In summary, our data confirm promising safety and efficacy of the treosulfan-based conditioning therapy in AML patients, ClinicalTrials.gov Identifier: NCT01063660.
  Bone marrow transplantation 12/2011; 47(9):1171-7. · 3.00 Impact Factor
• Article: KIR/HLA gene combinations influence susceptibility to B-cell chronic lymphocytic leukemia and the clinical course of disease.

  L Karabon, A Jedynak, S Giebel, D Wołowiec, M Kielbinski, D Woszczyk, K Kapelko-Slowik, K Kuliczkowski, I Frydecka
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  ABSTRACT: The aim of this study was to analyze the association between gene polymorphisms of killer-cell immunoglobulin-like receptors (KIRs) and their human leukocyte antigen (HLA) ligands and susceptibility to B-cell chronic lymphocytic leukemia (B-CLL) and the clinical course of disease. The distribution of individual KIR genes in 197 B-CLL patients and 200 controls was similar, except for a tendency for lower frequencies of the KIR2DS3 and KIR2DL5 genes among B-CLL patients (26.9% vs 35.5%, P = 0.06, 46.2% vs 55.5%, P = 0.06). The associations between KIR2DS3 and B-CLL reached statistical significance in women (P = 0.05). Moreover, we found a trend toward a lower frequency of genotypes with the presence of five or six activating KIR genes in B-CLL patients compared to controls (20.8% vs 29.0%, P = 0.06), and a significantly higher frequency of individuals possessing genotypes with a prevalence of inhibitory over activating KIR genes (ratio < 0.71) among B-CLL patients (P = 0.04). The HLA-Bw4 specificity was significantly reduced among B-CLL patients (48.7% vs 63.0%, P = 0.005), which resulted from a decreased frequency of HLA-Bw4(Thr80) (21.6% vs 32.0%, P = 0.02). Moreover, among HLA-Bw4-positive individuals, progression-free survival (PFS) tended to be higher in the presence of KIR3DS1 (77% ± 9% vs 39% ± 13%, P = 0.07). However, in B-CLL patients, the presence of HLA-C2 was associated with decreased PFS (49% ± 9% vs 75% ± 7%, P = 0.02), and among HLA-C2-positive patients, the probability of PFS was significantly reduced in the absence of KIR2DS1 (34% ± 11% vs 77% ± 7%, P = 0.007). Our results indicate that the pattern of inhibitory/activating KIR genes, together with their HLA ligands, is associated with susceptibility to B-CLL and affects the clinical course of this disease.
  Tissue Antigens 08/2011; 78(2):129-38. · 2.59 Impact Factor
• Article: Sequential recovery of NK cell receptor repertoire after allogeneic hematopoietic SCT.

  S Giebel, J Dziaczkowska, T Czerw, J Wojnar, M Krawczyk-Kulis, I Nowak, A Holowiecka, A Segatti, S Kyrcz-Krzemien, P Kusnierczyk, J Holowiecki
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  ABSTRACT: Alloreactivity of natural killer (NK) cells contributes to the GVL reaction after allogeneic hematopoietic SCT (allo-HSCT). However, various procedure-related factors may affect NK cell maturation and their ability to recognize and kill leukemic cells. In this study, we prospectively evaluated expression of NK cell inhibitory receptors in 83 adults treated with myeloablative, killer cell Ig-like receptor (KIR)-ligand-matched allo-HSCT. NK cell maturation was evaluated by comparing the phenotypic patterns after allo-HSCT with the donor ones. The frequencies of KIR3DL1 were comparable to the donor ones on day +28, while they decreased significantly starting from day +100. The expression of KIR2DL2/3 was significantly lower in patients compared with donors up to day +100. The expression of KIR2DL1, despite continues growth, remained significantly decreased for 1 year after allo-HSCT. NKG2A was over-expressed up to day +180. Within 1 year after allo-HSCT, the NK cell phenotypic pattern tended to recapitulate the donor type. The process was disturbed by the use of steroids with significant differences observed on days +56 (P=0.01) and +100 (P=0.04). Up to day +100, reconstitution of NK cell receptor repertoire correlated with the absolute numbers of circulating CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) cells. Our observations should be taken into account when trying to predict potential benefit from NK cell alloreactivity.
  Bone marrow transplantation 06/2010; 45(6):1022-30. · 3.00 Impact Factor
• Article: Status of minimal residual disease determines outcome of autologous hematopoietic SCT in adult ALL.

  S Giebel, B Stella-Holowiecka, M Krawczyk-Kulis, N Gökbuget, D Hoelzer, M Doubek, J Mayer, B Piatkowska-Jakubas, A B Skotnicki, H Dombret, J M Ribera, P P Piccaluga, T Czerw, S Kyrcz-Krzemien, J Holowiecki
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  ABSTRACT: The role of autologous hematopoietic SCT (autoHSCT) in the treatment of high-risk (HR) adult ALL is controversial. In this study, we retrospectively analyzed the results of autoHSCT according to the status of minimal residual disease (MRD) at transplantation, as a joint analysis of the European Study Group for Adult ALL (EWALL). Data on 123 recipients of autoHSCT, aged 31 (16-59) years, with B-lineage (n=77) or T-lineage (n=46) ALL were included. In a cohort of Ph-negative ALL, the probability of leukemia-free survival at 5 years was higher for patients with MRD <0.1% compared with those with MRD > or = 0.1% (57 vs 17%, P=0.0002). The difference was significant for T-lineage ALL (62 vs 8%, P=0.001), and a tendency was observed for B-lineage ALL (54 vs 26%, P=0.17). In a multivariate analysis, adjusted for other potential prognostic factors, high MRD level remained the only independent factor associated with increased risk of failure (risk ratio, 2.8; P=0.0005). We conclude that MRD determines the outcome of autoHSCT in HR adult ALL. Our results suggest the need to reevaluate the role of this treatment option in prospective trials.
  Bone marrow transplantation 10/2009; 45(6):1095-101. · 3.00 Impact Factor
• Article: 233. S. Giebel, M. Labopin, J. Holowiecki, B. Labar, M. Komarnicki, V. Koza, T. Masszi, M. Mistrik, A. Lange, A. Hellmann, A. Vitek, J. Pretnar, J. Mayer, P. Rzepecki, K. Indrak, W. Wiktor-Jedrzejczak, J. Wojnar, M. Krawczyk-Kulis, S. Kyrcz-Krzemien, V. Rocha: Outcome of HLA-matched related allogeneic hematopoietic stem cell transplantation for patients with acute leukemia in first complete remission treated in Eastern European centers. Better results in recent years.: Annals of Hematology (IF:

  S. Giebel, M. Labopin, J. Holowiecki, B. Labar, M. Komarnicki, V. Koza, T. Masszi, M. Mistrik, A. Lange, A. Hellmann, A. Vitek, J. Pretnar, J. Mayer, P. Rzepecki, K. Indrak, W. Wiktor-Jedrzejczak, J. Wojnar, M. Krawczyk-Kulis, S. Kyrcz-Krzemien, V. Rocha
  Annals of Hematology 01/2009; · 2.62 Impact Factor
• Article: Reply to Verheyden and Demanet.

  S Giebel, I Nowak, E Majorczyk, P Kusnierczyk
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 06/2008; · 8.30 Impact Factor
• Article: Association of KIR2DS4 and its variant KIR1D with leukemia.

  S Giebel, I Nowak, J Wojnar, M Krawczyk-Kulis, J Holowiecki, S Kyrcz-Krzemien, P Kusnierczyk
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 06/2008; 22(11):2129-30; discussion 2130-1. · 8.30 Impact Factor
• Article: Prediction of nonrelapse mortality for patients surviving 100 days after allogeneic hematopoietic stem cell transplantation.

  J Wojnar, S Giebel, A Holowiecka-Goral, M Markiewicz, I Wylezol, M Kopera, M Krawczyk-Kulis, J Holowiecki
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  ABSTRACT: Patients who survive 100 days after allogeneic hematopoietic stem cell transplantation (alloHSCT) are at risk for chronic graft-versus-host disease and other potentially fatal complications. As the symptoms overlap and the differential diagnosis is difficult, the goal of this study was to verify whether basic laboratory evaluation performed on day +100 may allow identification of patients who are at high risk for nonrelapse mortality (NRM), independent of the underlying complications. We analyzed 255 patients, mean age 29 years (range, 10-56 years), who remained alive and disease-free on day +100 after myeloablative alloHSCT from an HLA-identical sibling (n=177) or a matched unrelated volunteer (n=78), performed in a single institution between 1992 and 2003. Upon univariate analysis, the following laboratory parameters were associated with increased incidence of NRM: peripheral blood neutrophils<1.5x10(9)/L, platelets<100x10(9)/L, hemoglobin<11 g/dL, total protein<60 g/L, elevated plasma aspartate aminotransferase, elevated alkaline phosphatase, and elevated bilirubin. Upon multivariate analysis, only decreased protein (hazard ratio [HR]=6.97 [3.3-14.7], P<.0001) and elevated bilirubin (HR=3.52 [1.91-6.48], P<.0001) independently influenced the risk for NRM. The cumulative incidence of NRM equaled 6% if none of the above factors was present; 10% for hyperbilirubinemia alone; 22% for hypoproteinemia alone; and 70% for hyperbilirubinemia and hypoproteinemia, both present. A simple laboratory evaluation is highly predictive of the risk for NRM in patients surviving 100 days after alloHSCT. The prognosis is particularly poor for patients with hypoproteinemia and hyperbilirubinemia. These abnormalities may reflect impaired liver and intestine functions due to various posttransplantation complications.
  Transplantation Proceedings 12/2007; 39(10):3375-9. · 1.00 Impact Factor
• Article: Beta-2-microglobulin level predicts outcome following autologous hematopoietic stem cell transplantation in patients with multiple myeloma.

  B Stella-Holowiecka, T Czerw, A Holowiecka-Goral, S Giebel, J Wojnar, J Holowiecki
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  ABSTRACT: Despite the widespread use of high-dose therapy combined with autologous hematopoietic stem cell transplantation (autoHSCT), the outcomes of multiple myeloma (MM) treatment remain variable. The aim of this study was to define pretransplantation factors that influence outcomes following autoHSCT in patients with MM. Eighty-one MM patients, aged 51 years (range 31-70 years), undergoing first autoHSCT were included in the analysis. Thirty patients were in complete remission and 51 were in partial remission. The conditioning regimen was based mainly on melphalan (200 mg/m(2) intravenous [iv]). The following factors were tested for their prognostic significance: beta-2-microglobulin (B2M), lactate dehydrogenase, monoclonal protein level, bone marrow plasma cell percentage (PL), hemoglobin level, age, interval from diagnosis to autoHSCT, and number of transplanted CD34-positive cells. The transplant-related mortality at day 100 was 3.7% (3/81). The incidence of progression at 9.2 years was 71% for patients with elevated B2M, and 32% for those where B2M was within normal limits (P = .02.) The probability of PFS was decreased for patients with B2M > or = versus < normal limits (29% vs 68%; P = .02) and PL > or = versus < 5% (0% vs 45%; P = 0.03). In a multivariate analysis B2M remained the only factor associated with increased risk of progression (relative risk [RR] = 3.3; P = .03) and reduced probability of PFS (RR = 3.3; P = .03). We concluded that B2M level measured at first autoHSCT was a useful predictor for progression and PFS in MM patients.
  Transplantation Proceedings 11/2007; 39(9):2893-7. · 1.00 Impact Factor
• Article: Lymphocyte reconstitution after allogeneic bone marrow transplantation in a previously thymectomized patient--no evidence of extrathymic T-cell maturation.

  S Giebel, J Dziaczkowska, B Wysoczanska, J Wojnar, M Krawczyk-Kulis, A Lange, J Holowiecki
  Bone Marrow Transplantation 11/2007; 40(7):705-6. · 3.75 Impact Factor
• Article: Post-transplant induction of donor-type anti-RhD antibodies production shortly followed by complete hemolysis of recipient-type erythrocytes in RhD-mismatched allogeneic bone marrow recipient.

  M Markiewicz, J Wojnar, S Giebel, A Wieczorkiewicz, I Wylezoł, J Hołowiecki
  Bone Marrow Transplantation 03/2006; 37(4):433-4. · 3.75 Impact Factor
• Article: Unrelated donor bone marrow transplantation with treosulfan-based myeloablative conditioning for paroxysmal nocturnal hemoglobinuria--successful treatment despite multiple transplant-related risk factors for hemolysis including major Kidd group incompatibility.

  M Markiewicz, M Wojciechowska, I Wylezoł, K Woźniczka, S Giebel, J Wojnar, M Krawczyk-Kuliś, E Mendek-Czajkowska, J Hołowiecki
  Bone Marrow Transplantation 02/2006; 37(2):231-2. · 3.75 Impact Factor
• Article: The immunosuppressive effect of human cytomegalovirus infection in recipients of allogeneic hematopoietic stem cell transplantation.

  S Giebel, R Maccario, D Lilleri, M Zecca, M A Avanzini, M Marconi, A Di Cesare Merlone, G Campanini, D Montagna, P Travaglino, R Gentile, S Telli, D Pagliara, J Holowiecki, F Locatelli
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  ABSTRACT: In immune-competent individuals, human cytomegalovirus (HCMV) infection is associated with impairment of T-cell function. Our goal was to evaluate prospectively whether clinically asymptomatic HCMV infection in allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients, treated pre emptively with ganciclovir, influences T-cell function as well. Mitogen-stimulated T-cell proliferative activity, together with cell surface markers, was tested in 49 patients on days + 30, + 45, + 60, and + 90 after alloHSCT and, additionally, in cases of positive HCMV pp65-antigenemia. HCMV infection was diagnosed in 19 patients. None of them developed HCMV disease. T-cell proliferative activity was significantly decreased on days when HCMV antigenemia was positive as compared to days without antigenemia. The number of pp65-positive cells negatively correlated with proliferative response. Comparison of patients who did experience HCMV infection with those who did not reveals significant decrease of T-cell proliferative activity observed on days + 30 and + 45, a time period when antigenemia was most frequently found to be positive, whereas no difference was detected on days + 60 and + 90. We conclude that, even clinically asymptomatic, HCMV infection has negative impact on T-cell proliferation capacity in alloHSCT recipients. However, pre emptive therapy with ganciclovir makes this immunosuppressive effect transient and restricted to the time of infection duration.
  Bone Marrow Transplantation 10/2005; 36(6):503-9. · 3.75 Impact Factor
• Article: Imatinib therapy prior to myeloablative allogeneic stem cell transplantation.

  J M Zaucha, W Prejzner, S Giebel, T A Gooley, D Szatkowski, K Kałwak, J Wojnar, T Kruzel, J Balon, J Hołowiecki, A Hellmann
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  ABSTRACT: It is unknown whether imatinib prior to myeloablative haematopoietic stem cell transplantation (HSCT) increases transplant-related toxicity. Among the side effects induced by imatinib, myelosuppression and liver injury might worsen HSCT outcomes. We retrospectively analysed engraftment, liver toxicity, acute graft-versus-host disease (aGVHD) incidence and 100-day mortality in 30 patients with BCR/ABL-positive leukaemias who received imatinib before HSCT and compared results of 48 age-matched controls who did not receive preceding imatinib. Both neutrophil and platelet engraftment occurred more rapidly among imatinib patients but the differences adjusted for Gratwohl scale were not statistically significant (P = 0.18 and 0.22, respectively). The adjusted hazards of having liver function tests (LFTs) >1.5 normal increased and the adjusted durations of elevated LFTs were not significantly different. The estimated adjusted difference in mean peak bilirubin values was also not significantly different (P = 0.48). However, the adjusted hazard of increased creatinine >1.5 normal was significantly higher in the imatinib group (HR = 4.09, P = 0.02). The adjusted odds of grades II-IV aGVHD were similar in both groups (OR = 0.86, P = 0.78), and while the adjusted odds of 100-day mortality were lower among imatinib patients, the difference was not significant (OR = 0.65, P = 0.60). These data do not provide any evidence that imatinib preceding HSCT increases acute transplant-related toxicities.
  Bone Marrow Transplantation 10/2005; 36(5):417-24. · 3.75 Impact Factor
• Article: Allogeneic transplantation of selected peripheral CD34+ cells with controlled CD3+ cells add-back in high-risk patients.

  M Markiewicz, J Hołowiecki, J Wojnar, M Krawczyk-Kuliś, K Jagoda, S Giebel, T Kruzel
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  ABSTRACT: We evaluated the feasibility of allogeneic transplantation of CliniMACS-selected peripheral CD34+ cells from siblings (four patients: AML-M4, M2, CLL, MDS); nonoptimal related donors (two patients: AML-M4, CML); and unrelated donors (two patients: CML, ALL, both without engraftment after preceding URDBMT). All patients had high-risk of aGVHD and/or graft failure due to multiple transplantation risk factors. Conditioning treatment was myeloablative (n=7) or nonmyeloablative (n=1). Immunosuppression consisted of CsA (n=8), Mtx (n=5), ATG (n=4). Selected CD34+ cells were transplanted (average 3.91 x 10(6)/kg, range 1.29 to 7.27 x 10(6)/kg) together with 0.01 to 0.5 x 10(7) CD3+ cells/kg to assure proper engraftment. The remaining CD34-negative fraction was cryopreserved for further CD3+ cell add-back. Average recovery and purity of CD34+ cells following CliniMACS selection were 74% and 97%. No severe complications were observed in the first 100 days. Regeneration times were satisfactory in seven of eight patients (87.5%) with ANO > 0.5 g/L and Plt > 50 g/L reached on average on days +26 and +32 (range 15 to 29 and 15 to 67), respectively. In three patients (37.5%) T-lymphocytes were added-back one to three times (due to low numbers of initially transfused CD3+ cells in two patients, in one patient with PRCA caused by ABO incompatibility). One to four additional transplantations of nonselected peripheral cells were performed on days +28 to +270 in consequence of infections (CMV-two patients; parvovirus-one patient), poor regeneration and residual disease (one patient) and prolonged transfusion dependency (one patient). Severe aGVHD grade III or IV developed in three patients (37.5%) following the nonselected cells transplantation. Finally, five patients (62.5%) are alive and in remission (median follow-up 815 days). We conclude that allogeneic transplantation of selected peripheral CD34+ cells (CliniMACS) with controlled add-back of CD3+ cells is an effective, well, tolerated procedure in high-risk patients.
  Transplantation Proceedings 01/2005; 36(10):3194-9. · 1.00 Impact Factor
• Article: Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study.

  J Holowiecki, S Grosicki, T Robak, S Kyrcz-Krzemien, S Giebel, A Hellmann, A Skotnicki, W W Jedrzejczak, L Konopka, K Kuliczkowski, [......], J Kloczko, K Sulek, O Haus, B Stella-Holowiecka, W Baran, B Jakubas, M Paluszewska, A Wierzbowska, M Kielbinski, K Jagoda
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  ABSTRACT: To assess the efficacy of an original DAC-7 regimen: daunorubicine (DNR) 60 mg/m2/day, days 1-3; cytarabine (AraC) 200 mg/m2/day, days 1-7; cladribine (2-CdA) 5 mg/m2/day, days 1-5, 400 untreated adult acute myeloid leukemia patients (including 63 with preceding myelodysplastic syndrome), aged 45 (16-60) years were randomized to either DAC-7 (n=200) or DA-7 (without 2-CdA, n=200). The overall CR rate equaled 72% for DAC-7 and 69% for DA-7 arm (P=NS). After a single course of DAC-7 induction, the CR rate equaled 64% and was significantly higher compared to 47% in the DA-7 arm (P=0.0009). Median hospitalization time during the induction was 7 days shorter for DAC-7 compared to the DA-7 group (33 vs 40 days, P=0.002). Toxicity was comparable in both groups. The probability of 3-year leukemia-free survival (LFS) for DAC-7 and DA-7 group equaled 43 and 34%, respectively (P=NS). There was a trend toward higher LFS rate for patients aged >40 years receiving DAC-7 compared with DA-7 regimen (44 vs 28%, P=0.05). This study proves that addition of 2-CdA increases antileukemic potency of DNR+AraC regimen, thus resulting in a higher CR rate after one induction cycle when compared to DA-7, without additional toxicity. It shortens hospitalization time and may improve long-term survival in patients aged >40 years.
  Leukemia 06/2004; 18(5):989-97. · 9.56 Impact Factor
• Article: Treosulfan/fludarabine: a new conditioning regimen in allogeneic transplantation.

  J Casper, W Knauf, I Blau, T Ruutu, L Volin, H Wandt, K Schafer-Eckart, J Holowiecki, S Giebel, J Aschan, A Zander, N Kroger, G Doelken, M Freund
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  ABSTRACT: Recently, the water-soluble bifunctional alkylating agent treosulfan demonstrated broad stem cell toxicity, immunosuppressive as well as antileukemic activity. Due to its well known low non-hematologic toxicity profile, treosulfan was considered an alternative agent for conditioning prior to allogeneic transplantation. A first clinical study, combining 3 x 10 g/m2 of treosulfan with 5 x 30 mg/m2 of fludarabine, demonstrated the feasibility of this conditioning. A fast, reliable and complete development of the donor hematopoiesis was evident as well as a low non-hematologic toxicity, transplantation-related mortality and relapse rate. In a second study treosulfan was escalated from 3 x 10 to 3 x 12 and 3 x 14 g/m2. In this protocol, 55 pts (patients) not amenable to standard conditioning suffering from various hematological malignancies were included. Complete donor chimerism was reached by day 28 in 80% of the pts. So far, 8 pts (11%) died without disease progression and 11 pts (20%) relapsed. Treosulfan was very well tolerated. Especially no hepatic VOD, severe cardiac or pulmonary toxicity was noted. Acute GvHD (degrees 11-IV) occurred in 44% and chronic GvHD in 45% of pts. Considering the poor prognosis of these study populations, treosulfan-based conditioning is considered to be safe and efficient. New phase 11 clinical protocols in AML and MDS will be initiated.
  Annals of Hematology 02/2004; 83 Suppl 1:S70-1. · 2.62 Impact Factor
• Article: Low incidence of severe acute graft-versus-host disease in children given haematopoietic stem cell transplantation from unrelated donors prospectively matched for HLA class I and II alleles with high-resolution molecular typing.

  S Giebel, G Giorgiani, M Martinetti, M Zecca, R Maccario, L Salvaneschi, J Holowiecki, F Locatelli
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  ABSTRACT: We evaluated the outcome of 63 children given haematopoietic stem cell transplantation from unrelated donors (URD-HSCT) prospectively selected using DNA high-resolution typing of both HLA class I and class II loci. Thirty patient/donor pairs (48%) were fully matched. Among the others, HSCT was performed in the presence of one (n=22), two (n=9), or three (n=2) HLA disparities. Patients had either malignant (n=46) or non-malignant (n=17) disease. In all cases, graft-versus-host disease (GVHD) prophylaxis consisted of cyclospor-in A, short-term methotrexate and pretransplant anti-thymocyte globulin. The probability of haematopoietic recovery at day 100 was 97%. Two patients experienced primary graft failure. The cumulative probability of grades III-IV acute GVHD and of extensive chronic GVHD equalled 8 and 14%, respectively. A total of 12 patients died of transplant-related complications. The probability of transplant-related mortality (TRM) at 100 and 180 days was 10 and 15%, respectively, whereas the cumulative incidence of TRM was 22%. The probability of GVHD-related mortality equalled 6% at 2.5 years. The overall and disease-free survival rates were 67 and 65%, respectively. URD-HSCT with donor selection based on high-resolution HLA typing is associated with low incidence of both severe acute GVHD and graft failure. The observed outcome is comparable to that of children transplanted from HLA-identical siblings.
  Bone Marrow Transplantation 07/2003; 31(11):987-93. · 3.75 Impact Factor