Translocation t(4;14) Is Not an Adverse Prognostic Factor in Patients with Multiple Myeloma Undergoing Allogeneic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4743-4743
Author(s):  
Timon Hansen ◽  
Georgia Schilling ◽  
Avichai Shimoni ◽  
Jose-Antonio Simon-Perez ◽  
Wolfgang Bethge ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Univariate Analysis ◽  
Prognostic Impact ◽  
Event Free Survival ◽  
Free Survival

Abstract We analyzed the prognostic impact of the most frequent genetic abnormalities detected by fluorescence-in situ-hybridization combined with immunofluorescent cytoplasm immunoglobulin staining (cIg-FISH) in 101 patients with multiple myeloma, who underwent allogeneic stem cell transplantation after reduced melphalan/fludarabine-based conditioning from related (n=34) and unrelated (n=67) donors. The abnormalities were del(13q14) [62%], t(11;14)(q13;q32) [11%], t(4;14)(p16.3;q32) [16%], CMYC-gains (8q24) [17%], del(17p13.1) [16%], t(14;16)(q32;q23) [4%], whereas none of the patients had t(6;14)(p25;q32). Translocation t(4;14), CMYC-gains and del 17p were frequently associated with del(13q14): 64%, 80% and 92%, respectively. The complete remission (CR) rate was 45% for all patients. Patients with del(17p13) achieved fewer complete remission than others (7% vs. 56%; p=0.001), while no difference was seen for t(4;14) and other abnormalities. Univariate analysis revealed higher relapse rates for age > 50 years (p=0.002), del(13q14) (p=0.006) and del(17p13) (p=0.003). Patients with translocation t (4;14) had a similar four year event-free survival than others (50 vs 45%). In a multivariate analysis, only del(13q14) [HR: 2.34, p=0.03] and del(17p13) [HR: 2.24; p=0.04] influenced the risk of relapse, while for event-free survival, only age [HR 2.8; p=0.01] and del(17p13) [HR: 2.05; p=0.03] retained the prognostic value. These data seem to indicate that some adverse cytogenetic risk factors such as t(4;14) can be overcome by allogeneic stem cell transplantation, probably due to the graft versus myeloma effect. Del(17p13.1) is a significant factor for a lower chance of complete remissions and shorter event free survival following allogeneic stem cell transplantation. The presented data will have implications for risk-adapted strategies in the future.

Prognostic Significance of Molecular Remission Determined by Highly Specific PCR after Dose-Reduced Allogeneic Stem Cell Transplantation (SCT) in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4420-4420
Author(s):  
Maria V. Zagrivnaja ◽  
Anita Badbaran ◽  
Paolo Corradini ◽  
Boris Fehse ◽  
Axel R. Zander ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Prognostic Significance ◽  
High Rate ◽  
Molecular Remission

Abstract Achieving molecular remission after standard allogeneic stem cell transplantation in multiple myeloma is associated with long term freedom of disease and possible cure. We recently reported a high rate of complete remission after an auto-allo tandem approach using fludarabine (150 mg/m²), melphalan (140 mg/m²) and anti-thymocyte globulin (ATG: 3 x 10–20mg/kg) three months after a cytoreductive autograft (melphalan 200 mg/m²). To determine the incidence of molecular remission we tried to develop allele-specific oligonucleotides (ASO) based upon the clonal rearrangement of immunoglobulin heavy chain genes and ASO - polymerase chain reaction (ASO-PCR) for each patient who achieved complete remission with negative immunofixation after SCT (n=27). The specificity of the ASO-PCR was tested using patient and control DNA. Patient DNA isolated from bone marrow (BM) samples obtained at diagnosis and after allografting at variable time points was used for further molecular analysis. For nine patients we were able to generate specific primers and MRD diagnostics have been performed for a median of two years after SCT. Molecular remission was strictly defined by the absence of any PCR-positivity. In 6 patients nested PCR remained negative after a median follow up of 22 months (range 10–24). Only one of these patients relapsed with extramedullary disease (14 months) still being PCR-negative in his bone marrow. In contrast, all those patients with complete remission but positive PCR (n=3) relapsed (at 11, 14 and 16 months after SCT, respectively) thus underlining the importance of achieving molecular remission after allo-SCT. We suppose that quantitative real-time PCR might be a useful tool to closely monitor MRD kinetics post allo-transplantation in order to verify efficiency of various treatment regimens, e.g. donor lymphocyte infusions.

Reduced-Intensity Conditioning (RIC) Followed by Allogeneic Stem Cell Transplantation (SCT) for Relapsed Lymphomas: Impact of Pre-Transplantation Factors on Long-Term Outcome.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1129-1129 ◽  
Author(s):  
Paolo Corradini ◽  
Anna Dodero ◽  
Marco Bregni ◽  
Fabio Ciceri ◽  
Attilio Olivieri ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Univariate Analysis ◽  
Low Grade ◽  
Term Outcome ◽  
Long Term Outcome ◽  
The Impact

Abstract Allogeneic stem cell transplantation (SCT) represents a potentially curative treatment for recurrent lymphoid malignancies. In fact, potential advantages include the use of a tumor free graft and immune-mediated graft-versus-lymphoma effect. Here, we analyzed the impact of pre-transplantation factors on outcome in 141 lymphoma patients (pts) receiving RIC and allogeneic SCT from HLA-identical sibling donors. Histologic types included in the study were: low-grade non-Hodgkin lymphoma (LG-NHL; n=58), high-grade NHL (HG-NHL, n=55), Hodgkin disease (HD; n= 28). Median age was 50 years (range: 20–69). The three groups (HD vs LG-NHL vs HG-NHL) had similar characteristics in terms of: chemosensitive disease (57% vs 69% vs 67%, p=ns) and complete remission (CR) at transplant (18% vs 27% vs 34%, p=ns). Pts with HD had received more lines of chemotherapy (>2 vs ≤2) as compared to LG-NHL and HG-NHL (82% vs 52% vs 42%). Furthermore, the proportion of pts receving previous autologous SCT was significantly higher in HD and HG-NHL versus LG-NHL (75% vs 54% vs 27%). In addition, patients with HG-NHL and HD underwent frequently allo-SCT less than 2 years after diagnosis as compared to LG-NHL (58% vs 39% vs 24%). All patients received debulkying chemotherapy followed by the same RIC containing thiotepa (10 mg/kg), fludarabine (60 mg/ms) and cyclophosphamide (60 mg/kg). GVHD prophylaxis consisted of cyclosporine A and short-course methotrexate. At a median follow-up of 30 months (8–70), the overall survival (OS) and progression-free survival (PFS) were 65% (95%CI, 56–74%) and 57% (95%CI, 47%–67%), respectively. Univariate analysis showed that age (< or > 55 years), donor sex, interval between diagnosis and SCT, number of previous treatments did not influence outcome whereas diagnosis of HD was associated with a significant inferior PFS and OS. Chemosensitive disease (CR+PR) influenced PFS in HG-NHL (p<0.0003) and HD (p<0.0036) but not in LG-NHL (p=0.69). Complete remission at transplant was associated to a significant better PFS in HD (p<0.01) but not in HG-NHL (p= 0.14) and LG-NHL (p=0.7). Previous autologous SCT was associated to inferior PFS (64% vs 50%, p<0.04) but did not affected OS and TRM. By multivariate analysis, diagnosis of HD and refractory disease were associated to an inferior PFS (p<0.0001, p<0.001) whereas diagnosis of HD and no-CR at transplant remained of prognostic value on OS (p<0.006 and p<0.007). We conclude: 1) age and previous treatments, including autologous SCT, are no longer limitations for allogeneic SCT; 2) debulking therapy before RIC allogeneic SCT is required for HD and HG-NHL; 3) new strategies for an early indentification of chemorefractory pts are necessary.

scholarly journals Allogeneic stem cell transplantation for AML patients with RUNX1 mutation in first complete remission: a study on behalf of the acute leukemia working party of the EBMT

2021 ◽  
Author(s):  
Johanna Waidhauser ◽  
Myriam Labopin ◽  
Jordi Esteve ◽  
Nicolaus Kröger ◽  
Jan Cornelissen ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Working Party ◽  
Free Survival ◽  
Mutational Status ◽  
First Complete Remission

AbstractAcute myeloid leukemia with runt-related transcription factor 1 gene mutation (RUNX1+ AML) is associated with inferior response rates and outcome after conventional chemotherapy. We performed a retrospective, registry-based analysis to elucidate the prognostic value of RUNX1 mutation after allogeneic stem cell transplantation (alloSCT). All consecutive adults undergoing alloSCT for AML in first complete remission (CR1) between 2013 and 2019 with complete information on conventional cytogenetics and RUNX1 mutational status were included. Endpoints of interest were cumulative relapse incidence, non-relapse mortality, overall and leukemia-free survival (OS/LFS), and GvHD-free/relapse-free survival. A total of 674 patients (183 RUNX1+, 491 RUNX1−) were identified, with >85% presenting as de novo AML. Median follow-up was 16.4 (RUNX1+) and 21.9 (RUNX1−) months. Survival rates showed no difference between RUNX1+ and RUNX1− patients either in univariate or multivariate analysis (2-year OS: 67.7 vs. 66.1%, p = 0.7; 2-year LFS: 61.1 vs. 60.8%, p = 0.62). Multivariate analysis identified age, donor type and poor cytogenetics as risk factors for inferior outcome. Among patients with RUNX+ AML, older age, reduced intensity conditioning and minimal residual disease at alloSCT predicted inferior outcome. Our data provide evidence that the negative influence of RUNX1 mutations in patients with AML can be overcome by transplantation in CR1.

scholarly journals Comparison Between 5-Azacytidine Treatment and Allogeneic Stem-Cell Transplantation in Elderly Patients With Advanced MDS According to Donor Availability (VidazaAllo Study)

2021 ◽  
pp. JCO.20.02724
Author(s):  
Nicolaus Kröger ◽  
Katja Sockel ◽  
Christine Wolschke ◽  
Wolfgang Bethge ◽  
Richard F. Schlenk ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Event Free Survival ◽  
Reduced Intensity Conditioning ◽  
Treatment Allocation ◽  
Free Survival ◽  
Reduced Intensity

PURPOSE In contrast to 5-azacytidine (5-aza), allogeneic stem-cell transplantation (HSCT) represents a curative treatment strategy for patients with myelodysplastic syndromes (MDS), but therapy-related mortality (TRM) limits its broader use in elderly patients with MDS. The present prospective multicenter study compared HSCT following 5-aza pretreatment with continuous 5-aza treatment in patients with higher-risk MDS age 55-70 years. METHODS One hundred ninety patients with a median age of 63 years were enrolled. Patients received 4-6 cycles of 5-aza followed by HLA-compatible HSCT after reduced-intensity conditioning or by continuous 5-aza if no donor was identified. RESULTS Twenty-eight patients did not fulfill inclusion criteria (n = 20), died (n = 2) withdrew informed consent (n = 5), or were excluded for an unknown reason (n = 1). 5-aza induction started in 162 patients, but only 108 (67%) were eligible for subsequent allocation to HSCT (n = 81) or continuation of 5-aza (n = 27) because of disease progression (n = 26), death (n = 12), or other reasons (n = 16). Seven percent died during 5-aza before treatment allocation. The cumulative incidence of TRM after HSCT at 1 year was 19%. The event-free survival and overall survival after 5-aza pretreatment and treatment allocation at 3 years were 34% (95% CI, 22 to 47) and 50% (95% CI, 39 to 61) after allograft and 0% and 32% (95% CI, 14 to 52) after continuous 5-aza treatment ( P < .0001 and P = .12), respectively. Fourteen patients progressing after continuous 5-aza received a salvage allograft from an alternative donor, and 43% were alive at last follow-up. CONCLUSION In older patients with MDS, reduced-intensity conditioning HSCT resulted in a significantly improved event-free survival in comparison with continuous 5-aza therapy. Bridging with 5-aza to HSCT before is associated with a considerable rate of dropouts because of progression, mortality, and adverse events.

scholarly journals Prognostic Impact of Adverse Chromosomal Abnormalities on Outcome of Allogeneic Stem Cell Transplantation in Hyperdiploid Variant of Acute Myeloid Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5234-5234
Author(s):  
Tatiana L Gindina ◽  
Mamaev N Nikolay ◽  
Bondarenko N Sergey ◽  
Slesarchuk A Olga ◽  
Anastasiya S Borovkova ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chromosomal Abnormalities ◽  
Clinical Status ◽  
Prognostic Impact ◽  
Modal Number ◽  
Free Survival

Abstract Background. Chromosome gain is frequent in acute myeloid leukemia (AML) and is counted alongside structural abnormalities when determining karyotype complexity. Meantime, there are no studies investigating the cytogenetic profile and outcome of patients with a hyperdiploid variant (HV, ³47 chromosomes) of AML after allogeneic stem cell transplantation (allo-HSCT). Aim. To evaluate the prognostic impact of different cytogenetic characteristics, including the modal number, the number of chromosomal aberrations in complex karyotype (CK), the adverse chromosomal abnormalities (ACA) (monosomy 7/7q-, monosomy 5/5q-, monosomy 17/17p-,t(6;9)(p22;q34) on results of allogeneic stem cell transplantation (allo-HSCT) in patients with HV of AML. Material and methods.Forty-seven patients with HV of AML (21 women and 26 men, aged from 1 to 58 years, median - 23,9 years) were examined.Analysis of overall and event-free survival predictors after allo-HSCT in patients with different clinical, transplant and cytogenetic characteristics was performed. Results. The most common in the karyotype was the modal number of chromosome (MN) 47-48 which was observed in 31 (66 %) patients.Highhyperdiploidy with the modal number 49-65 wasidentified in13 (28 %) patients, near-triploidy and near-tetraploidy karyotypes were found in3 (6%) patients. Chromosomes were gained in a nonrandom pattern. Chromosome 8 (50 %), 21 (32 %), 13 (16 %)è 22 (16 %) were the most commonly gained. Structural chromosomal abnormalities were detected in 22 (47 %) patients, and the adverse chromosomal abnormalities were revealed in 7 (19 %) patients.In univariate analysis, overall survival (OS) and event-free survival (EFS) were various in patients with differentdisease status at transplantation (remission vs active disease; p=0.003 and p=0.002, respectively) and adverse chromosomal abnormalities inhyperdiploid karyotype (ACA- vs ACA+; p=0.001 and p=0.03, respectively). Additional analysis of selected patients group with structurally complex karyotype (n=19) showedthat the patients without ACA had OS higher than patients with ACA (p=0.03).In multivariate analysis, independent predictors of decreased OS and EFS were active disease at allo-HSCT (p=0.004èp=0.006, respectively) and the presence of the ACA (p=0.002 only for OS). Conclusion. High-risk factors in patients with HV of AML treated by allo-HSCT are adverse chromosomal aberrations. Therefore, the patients with formal criteria Çcomplex karyotypeÈ should not automatically be assigned to the adverse cytogenetic risk group on the basis of complexity. Instead they should be assessed for the presence of specific chromosomal abnormalities, which are known to harbor an adverse effect. Table 1 Patients and Transplant characteristics Table 1. Patients and Transplant characteristics Table 2 Multivariate analyses Table 2. Multivariate analyses Figure Overall survival depending on clinical status at HSCT and the presence of adverse chromosomal abnormalities (-7/7q-,5q-,17p-,t(6;9) in patients with a hyperdiploid variant of AML. Figure. Overall survival depending on clinical status at HSCT and the presence of adverse chromosomal abnormalities (-7/7q-,5q-,17p-,t(6;9) in patients with a hyperdiploid variant of AML. Disclosures No relevant conflicts of interest to declare.

Impact of Induction Chemotherapy With Intermediate-Dosed Cytarabine and Subsequent Allogeneic Stem Cell Transplantation on the Outcome of High-Risk Acute Myeloid Leukemia

2021 ◽  
Author(s):  
Maximilian Fleischmann ◽  
Ulf Schnetzke ◽  
Jochen J Frietsch ◽  
Herbert G Sayer ◽  
Karin G Schrenk ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Induction Chemotherapy ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Intensive Care Treatment ◽  
Free Survival

Abstract BackgroundAcute myeloid leukemia (AML) with antecedent hematological disease (s-AML) and treatment-related AML (t-AML) predict poor prognosis. Intensive treatment protocols of those highrisk patients should consider allogeneic stem cell transplantation (ASCT) in first complete remission (CR). Despite ASCT, relapse rate remains high. Induction chemotherapy with liposomal cytarabine and daunorubicin (CPX-351) has been approved for patients with AML with myeloid-related changes (AMLMRC) or t-AML based on improved survival and remission rates compared to standard 7+3 induction. Patients and Methods110 patients with newly diagnosed s-AML or t-AML at a university hospital were analyzed retrospectively. Median age was 62 years (24-77 years). A total of 65 patients with s-AML after MDS (59%) and 23 patients (20.9%) with t-AML were included. Induction chemotherapy consisted of intermediate-dosed cytarabine (ID-AraC) in combination with idarubicin (patients up to 60 years) or mitoxantrone (patients over 60 years). In patients subsequently undergoing ASCT reduced conditioning regimens (RIC) were applied prior to transplantation in 47 of 62 patients (76%). ResultsInduction chemotherapy with ID-AraC resulted in an overall response rate of 83% including complete remission (CR/CRi) in 69 patients (63%) with a low rate of early death (2.7%). Most relevant non-hematologic toxicity consisted of infectious complications including sepsis with need of intensive care treatment in five patients (4.5%) and proven or probable invasive fungal disease in 8 patients (7.2%). Relapse-free survival (RFS), event-free survival (EFS) and overall survival (OS) of the whole cohort were 19 months (0-167), 10 months (0-234) and 15 months (0-234), respectively (p<0.0001). A significant improvement of OS was observed in patients who underwent ASCT compared to those without subsequent ASCT: 9 months vs. 46 months, p<0.0001. Rate of transplantation-related mortality (TRM) in the early phase post ASCT was low (0.9% at day 30 and 1.8% at day 90, respectively). RIC conditioning results in OS rate of 60% after 60 months post ASCT (median OS not reached). ConclusionS-AML and t-AML patients receiving induction chemotherapy with intermediate-dosed cytarabine showed satisfactory response rate and consolidation therapy with ASCT after full or reduced intensity conditioning further improved survival in these patients with similar outcome as reported for CPX-351.

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