scholarly journals Allogeneic Stem Cell Transplantation for Primary or Secondary Myelofibrosis: A Retrospective Intent-to-Treat Analysis and Impact of Mutational Status and JAK1/2 Inhibitor Ruxolitinib Prescription in Patients Who Cannot Proceed to Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3218-3218
Author(s):  
Elsa Lestang ◽  
Pierre Peterlin ◽  
Yannick Le Bris ◽  
Jacques Delaunay ◽  
Viviane Dubruille ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Triple Negative ◽  
Univariate Analysis ◽  
Allogenic Stem Cell Transplantation ◽  
Mutational Status ◽  
The Impact

Abstract Introduction: Allogenic stem cell transplantation (Allo-SCT) remains currently the only curative treatment for primary myelofibrosis (PMF) or myelofibrosis secondary (SMF) to essential thrombocythemia (ET)/polycythemia vera (PV). Indication of allo-SCT refers to high-risk patients defined by various scores such as Lille score, IPSS, DIPSS or more recently DIPSS+. However, JAK2, CALR, MPL or triple negative mutation profiles have recently been shown to impact on the outcome of PMF patients and thus may challenge the indication of allo-SCT in the future. CALRmut patients seem to have the best survival conversely to triple-negative patients, while JAK2mut and MPLmut status can be considered as an intermediate molecular signature (Tefferi, Leukemia 2014). The outcome of MF patients with a validated allo-SCT indication who do not proceed to transplant is generally unknown although relatively long survival can be documented, especially since the availability of JAK inhibitors such as ruxolitinib. Also, data regarding impact of mutational status on outcome after allo-SCT remain scarce. Patients and Methods: This single-center retrospective study considered MF patients with a validated indication of allo-SCT between 2000 and 2013. The main objective was to compare the overall survival (OS) between patients who ultimately received allo-SCT or not. Secondary objectives were to analyze the impact of mutational molecular status on OS and the use of ruxolitinib in patients not allografted. Results: An indication of allo-SCT was validated in 67 patients (males: 64%; PMF: 59%; SMF post-ET 25%, SMF post-PV 16%). At the time of indication of ASCT, the median age was 59 years (range: 41-69); DIPSS+ score was: int-2 in 40%, high risk in 60%. Mutational status, available for 86% of patients, was as follows: JAK2V617F (n=37), CALRmut (n=12); MPLmut (n=3), triple-negative (n=6). Thirty-three patients proceeded to allo-SCT (reduced intensity conditioning: 82%) while 34 did not for lack of donor (31%), comorbidity (28%), progressive disease (14%), stable disease on conventional therapy (18%), refusal (9%). The two groups (allo/non-allo SCT) were comparable for gender, year of indication of allo-SCT, type of MF, number of prior lines of treatment before allo-SCT, DIPSS+ categorization, mutational status and median follow-up. Patients who did not proceed to allo-SCT were significantly older (61 vs 57 years, p<0.005). Two allografted patients received ruxolitinib after transplant while 9 patients received it after invalidation of the transplant procedure. With a median follow-up of 44 months, median OS was 57 months for the whole cohort. A significantly lower OS was associated to unfavorable karyotype (median: 17 vs 100 months, HR: 2.6, 95%CI: 1.1-6.5, p=0.02), higher percentage of circulating blasts at time of indication of SCT (HR: 1.15, 95%CI: 1.01-1.32, p=0.01) and higher DIPSS+ score (HR: 1.3, 95%CI: 1.01-1.6 p=0.01). There was a trend for a better OS in CALRmut patients compared to other patients (median not reached (NR) vs 35 months, HR: 0.63, 95%CI: 0.25-1.51, p=0,3), especially vs triple-negative patients (NR vs 15 months, HR:0.29, 95%CI: 0.09-0.9 p=0.025). Five-year OS was similar between both groups (allo: 51% vs non-allo 44%, p=ns). However, progression to myelodysplastic syndrome or acute myeloid leukemia was significantly lower for allografted patients (19.2% vs 44.5%, p=0.01). In univariate analysis, allo-SCT benefited to patients with SMF post TE/PV (median OS: allo 115 vs non-allo 18.4 months, HR: 0.18, 95%CI: 0.05-0.5, p=0.004), unfavorable karyotype (median OS: allo: NR vs non-allo 7.9 months, HR: 0.13, 95%CI: 0.04-0.4, p=0.002) or high DIPSS+ score (median OS: allo 120 vs non-allo 18 months, HR:0.41, 95%CI: 0.16-0.9, p=0.04). Also there was a trend for better OS in allografted patients with high JAK2V617F burden (>65%) (median OS: NR vs 18 months, HR: 0.18, 95%CI:0.03 -1.11, p=0.065). Interestingly, the survival of patients who did not proceed to allo-SCT was increased by the use of ruxolitinib (median OS: NR vs 20 months, HR: 2.3, 95%CI: 0.08-0.6, p=0.003). Conclusion: Allo-SCT remains a valid strategy for high-risk MF patients with unfavorable karyotype, high DIPSS+ score and secondary MF while impact of mutational status and JAK2V617F burden have to be confirmed in larger studies. MF patients who cannot proceed to transplant likely benefit from JAK2 inhibitor prescription. Disclosures Milpied: Celgene: Honoraria, Research Funding. Moreau:Celgene, Janssen, Takeda, Novartis, Amgen: Membership on an entity's Board of Directors or advisory committees.

Low Relapse without Excessive Transplant-Related Mortality Following Allogeneic Stem Cell Transplantation in Patients with High Risk Secondary Acute Myeloblastic Leukaemia and Myelodysplastic Syndromes, Long-Term Outcomes in a Single Centre Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4308-4308
Author(s):  
Jean El-cheikh ◽  
Luca Castagna ◽  
Sabine Furst ◽  
Catherine Faucher ◽  
Benjamin Esterni ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Allogenic Stem Cell Transplantation ◽  
Related Mortality

Abstract Abstract 4308 Allogenic stem cell transplantation (Allo-SCT) as a therapy for secondary acute myeloid leukaemia (sAML) and myelodisplastic syndromes (MDS) is the most powerful treatment option. However, (Allo-SCT) is also complicated by a high risk for treatment-related morbidity and mortality. We analysed retrospectively the data of 70 patients transplanted at our institution from June 1995 to december 2008, 44 patients (63%) with sAML and 26 patients (37%) with MDS was treated with (Allo-SCT); median age at diagnosis was 41 years, (15-70), and the median age of 42, 5 years (16-70) at transplantation; The conditioning regimen was myeloablative combining (cyclophosphamide and TBI) in 16 patients (23%) and 54 patients (77%) was with a reduced intensity conditioning (RIC) regimens combining fludarabine, busulfan, and antithymocyte globulin; 11 patients (16%) were infused with bone marrow (BM), 55 patients (79%) peripherical blood stem cells (PBSC), and 4 patients (5%) cord blood cells; in 49 cases (70%) donor was a HLA identical sibling and in 21 (30%) was a matched unrelated donor; 41 patients (59%) carried high risk cytogenetic features, like (7q-, 5q-, > 3 alterations), while was normal in 24 patients (34%), and in 5 patients (7%) was unknown. Disease status at transplantation was as follow: CR in 24 patients (34%), 34 patients (49%) was refractory or in progression after treatment, and 12 patients (17%) was with a stable disease. With a median follow-up of 55 months (3-150), 30 patients (43%) are alive, the overall survival OS at 2 years and 5 years was 48 % and 39% respectively, and after ten years of follow up, OS was 30%, 95%CI [17.8-50.8]. We observed also that 26 % of refractory patients and 54% of patients in CR are alive at five years of transplantation. The probability of progression after transplantation at five and ten years was 31% with 95%CI [20.-46.5]. 2 years and 5 years treatment related mortality (TRM) was 23% and 26% respectively, and no modification at ten year, 95%CI [14.3-37.3]. TRM occurred in 16 patients (23%). Cause of death was; infections in 5 patients (7%), GvHD in 3 patients (4%), GvHD and infection in 3 patients (4%), multi organ failure (MOF) in 5 patients (7%). In multivariate analysis; OS, PFS or TRM, were not influenced by donor type (HLA id sibling vs others), conditioning regimen (RIC vs MAC), and stem cell source (bone marrow vs PBSC). Allogenic stem cell transplantation can be considered as a good option for the treatment of patients with high risk sAML and MDS when compared with the remission rate at five years of the other nonallogeneic SCT therapies. Disclosures: No relevant conflicts of interest to declare.

A Reduced Rate of Leukaemia Relapse After HLA-Identical Sibling Stem Cell Transplantation for Acute Myeloid Leukaemia but Not Other Haematological Malignancies Is Associated with Donor KIR Genes 2DL5A, 2DS1 and 3DS1.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2282-2282
Author(s):  
Kate Stringaris ◽  
Sharon Adams ◽  
Marcela Uribe ◽  
Rhoda Eniafe ◽  
Colin Wu ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Univariate Analysis ◽  
Haematological Malignancies ◽  
Kir Genes ◽  
Cell Dose ◽  
High Risk Disease

Abstract Abstract 2282 Poster Board II-259 Stem cell transplantation (SCT) from a healthy donor can be curative for patients with haematological malignancies resistant to other treatments. Elimination of malignant cells through a graft-versus-leukaemia (GVL) effect involves donor T- and NK-cells but their relative contribution to this process is poorly defined. NK-cell alloreactivity and GVL effects are controlled by the nature of the interaction of NK activation receptors and killer-immunoglobulin-like-receptors (KIR) with major-histocompatibility locus class I antigens on thetarget cell. We performed KIR-genotyping of HLA-matched donors in two hundred and forty eight T-celldepleted SCTs to identify genetic factors affectingtransplant outcome (transplant-related mortality (TRM), leukaemic relapse and survival). Transplant-related factors and donor KIRgenotyping significant in univariate analysis were entered into a multivariateanalysis to identify independent variables predictive of outcome for differentforms of leukaemia. Patients studied were transplanted at a single center between 1993-2008.They included 70 AML, 99 CML, 40 ALL, 39 MDS patients and 13 patients with CLL, NHL or Myeloma. Median age was 36 years (range 9-66). All received aT cell depleted SCT from an HLA identical sibling. Patients were conditioned with totalbody irradiation 12-13.5Gy (4Gy for patients over 55y) and cyclophosphamide120mg/kg +/- fludarabine 125mg/m2. Patients received 0.2-5 × 10 5 CD3 cells /kg and amedian CD34 cell dose of 3 × 10 6/kg. Cyclosporine was used as the sole GVHDprophylaxis. Multivariate analysis confirmed known predictive factors; for survival: highCD34 cell dose(RR 0.51, p <0.001) and standard rather than high risk disease (RR 3.1, p <0.001), for TRM: poor lymphocyte recovery at day 30 (RR 0.4, p < 0.02), for relapse: high risk disease (RR 4.65, p<0.002). In addition, the presence of donor B haplotype KIR genes: 2DL5A, 2DS1 and 3DS1was associated with significantly less relapse in patients with AML (13% vs 57% ) but not inpatients with other myeloid or lymphoid malignancies. AMLpatients receiving SCT from donors with these KIR genesspan style=“font-size: 10pt;”>relapsed five times less frequently than patientstransplanted from donors with other KIR genotypes.No other factors relating to NK alloreactivity including (missing donor KIR ligand, presence of donor haplotype B, total number of inhibitory KIR and total number of activatory KIR) was foundto be predictive for transplant outcomes. Thesefindings suggest specific, genetically determined,interactions between NK-cells and AML cells whichfacilitate the graft-versus-leukaemia effect and haveimplications for donor selection for AML patients. Disclosures: No relevant conflicts of interest to declare.

Cytomegalovirus Infection and Lymphopenia Are Associated with Increased Mortality Post Autologous Stem Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4208-4208
Author(s):  
Alessandro de Moura Almeida ◽  
Erika Maria Macedo ◽  
Claudia Mac Donald Bley ◽  
Fabio R. Kerbauy ◽  
Paulo Vidal Campregher ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hodgkin’S Lymphoma ◽  
Univariate Analysis ◽  
Hodgkin's Lymphoma ◽  
Prognostic Impact ◽  
Cmv Infection

Abstract Abstract 4208 Introduction: Despite preventive and therapeutic antiviral medication cytomegalovirus (CMV) infection is still a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (SCT). Only limited data on CMV infection and disease are available in autologous SCT recipients. Previous studies have demonstrated that the probability of CMV infection is nearly 60% in seropositive patients and 23% in seronegative patients undergoing autologous SCT, but its impact in mortality is unclear. Methods: We retrospectively reviewed the medical records of 101 patients undergoing autologous SCT at Hospital Israelita Albert Einstein from January, 2005 to July, 2012. CMV infection was defined as a quantitative real time PCR assay showing greater than 165 copies and/or positive CMV pp65 antigenemia assay. Lymphocyte count was registered at 15th day after SCT and lymphopenia was defined as an absolute lymphocytes count (ALC) < 500 at that time point. Overall survival (OS) was estimated from the time of transplant until death, with surviving patients censored at last follow-up. Variables entered into the multivariate Cox analysis were those with a p-value <0.10 in the univariate analysis. CMV infection was analyzed as a time-dependent covariate, considering the time to CMV infection. Statistical analysis was performed with STATA (v11.0) and alfa error was defined as 5%. Results: The majority of patients were male (62.4%) and the median age was 58 years old (range: 3–76). Peripheral stem cell harvest was the main source of cells (92%). A positive serological CMV status was found in 93.75% of patients. Most common indications for autologous SCT were multiple myeloma (34%), non-Hodgkin's lymphoma (40%) and Hodgkin's lymphoma (6%). After a median follow-up of 2 years, the OS for the whole cohort was 61% (95% confidence interval [CI] 48–72%). CMV infection post SCT was seen in 26% of patients. In the univariate analysis, development of CMV infection and presence of D15 lymphopenia were associated with a higher mortality (CMV infection-hazard ratio [HR] 3.32 [95%IC 1.61–6.84]; p= 0.001; D15 lymphopenia- HR 2.37 [95% IC 1.11–5.05]; p= 0.024). Patients who developed CMV infection in the setting of D15 lymphopenia had the worse outcome (2-years OS 19%; 95% CI 9–43%; figure 1). D15 lymphopenia was not associated with a higher rates of CMV infection (p=0.41). In Cox multivariate analysis, lower overall survival was demonstrated in female patients (HR= 2.23, 95%IC 1.08–4.58; p= 0.029), in the presence of D15 lymphopenia (HR= 2.56, 95%IC 1.19–5.51; p= 0.016) and CMV infection (HR: 3.33, 95% IC1.61–46.86; p= 0.001). Conclusion: CMV infection post-autologous SCT is associated with a decreased survival, and in the concomitant presence of D15 lymphopenia appears to indicate a subgroup of patients with very poor outcome. It is possible that CMV infection does not lead directly to increased mortality, but is rather a surrogate marker of decreased immune function post-ASCT. Future studies should prospectively evaluate the incidence and prognostic impact of CMV infection post-ASCT and correlate with markers of immune recovery. Disclosures: No relevant conflicts of interest to declare.

Long-term health status of high-risk neuroblastoma survivors treated with high-dose chemotherapy and hematopoietic stem cell transplantation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10054-10054 ◽  
Author(s):  
Sandrine Haghiri ◽  
Chiraz Fayech ◽  
Christelle Dufour ◽  
Claudia Pasqualini ◽  
Stephanie Bolle ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Second Cancers

10054 Background: Current treatment strategies including high-dose chemotherapy with stem cell transplantation rescue (HDC-SCT) have improved 5-year event-free survival for high-risk neuroblastoma (HRNB) patients, but with an increased risk of late treatment-related toxicities. Methods: Between 1980 and 2012, 439 children were treated for HRNB with HDC-SCT in Gustave Roussy (GR), among which 145 were alive and disease-free at 5-year post-SCT. Long-term health data have been collected for those 145 patients, prospectively within the long-term follow-up clinic in GR or retrospectively from pediatric consultations. Results: With a median follow-up post-SCT of 15 years (range 5-34), we observed 6 late relapses, 11 second cancers (including 3 papillary thyroid carcinomas; median delay = 20 years post-SCT [18-22]) and 9 deaths. Event-free and overall survival at 20-year post-SCT were 82% (95%CI = 70–90) and 89% (95%CI = 78–95), respectively. A second health event was observed in 135 patients (median = 3/patient), including 103 patients with at least 1 severe event (median = 1/patient). Cumulative incidence at 15-year post-SCT for second cancers is 4%, cardiac diseases 8%, thyroid 11%, renal 7%, hepatic focal nodular hyperplasia 14%, dental mal-development 70%, and severe hearing loss 20%. Height-for-age z-score was ≤-2 for 30 patients (21%) and ≤-3 for 12 patients (8%). After Busulfan-Melphalan conditioning regimen, 40/43 females and 33/35 males had a gonadal insufficiency. Conclusions: Long-term consequences of HRNB treatment including HDC are frequent and disabling, mainly due to hearing loss and gonadal insufficiency.

Impact of Azacitidine Before Allogeneic Stem-Cell Transplantation for Myelodysplastic Syndromes: A Study by the Société Française de Greffe de Moelle et de Thérapie-Cellulaire and the Groupe-Francophone des Myélodysplasies

2012 ◽  
Vol 30 (36) ◽  
pp. 4533-4540 ◽  
Author(s):  
Gandhi Damaj ◽  
Alain Duhamel ◽  
Marie Robin ◽  
Yves Beguin ◽  
Mauricette Michallet ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Underlying Disease ◽  
International Prognostic Scoring System ◽  
Cytoreductive Treatment ◽  
Thérapie Cellulaire ◽  
The Impact

Purpose To investigate the impact of prior-to-transplantation azacitidine (AZA) on patient outcome after allogeneic stem-cell transplantation (alloSCT) for myelodysplastic syndrome (MDS). Patients and Methods Of the 265 consecutive patients who underwent alloSCT for MDS between October 2005 and December 2009, 163 had received cytoreductive treatment prior to transplantation, including induction chemotherapy (ICT) alone (ICT group; n = 98), AZA alone (AZA group; n = 48), or AZA preceded or followed by ICT (AZA-ICT group; n = 17). At diagnosis, 126 patients (77%) had an excess of marrow blasts, and 95 patients (58%) had intermediate-2 or high-risk MDS according to the International Prognostic Scoring System (IPSS). Progression to more advanced disease before alloSCT was recorded in 67 patients. Donors were sibling (n = 75) or HLA-matched unrelated (10/10; n = 88). They received blood (n = 142) or marrow (n = 21) grafts following either myeloablative (n = 33) or reduced intensity (n = 130) conditioning. Results With a median follow-up of 38.7 months, 3-year outcomes in the AZA, ICT, and AZA-ICT groups were 55%, 48%, and 32% (P = .07) for overall survival (OS); 42%, 44%, and 29% (P = .14) for event-free survival (EFS); 40%, 37%, and 36% (P = .86) for relapse; and 19%, 20%, and 35% (P = .24) for nonrelapse mortality (NRM), respectively. Multivariate analysis confirmed the absence of statistical differences between the AZA and the ICT groups in terms of OS, EFS, relapse, and NRM. Conclusion With the goal of downstaging underlying disease before alloSCT, AZA alone led to outcomes similar to those for standard ICT.

scholarly journals PB2382 FOLLOW UP POST ALLOGENIC STEM CELL TRANSPLANTATION IN MOROCCO: ABOUT 28 PATIENTS

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 1059-1060
Author(s):  
S. Haidouri ◽  
K. zine Filali ◽  
M. ababou ◽  
E. mahtat ◽  
M. mikdame ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogenic Stem Cell Transplantation

Long term follow up of patients with locally advanced triple negative breast cancer treated with adjuvant high dose chemotherapy and autologous stem cell transplantation: A single center experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12590-e12590
Author(s):  
Sani Mohammed Bukari ◽  
Muhammad Usman ◽  
Judith Abrams ◽  
Voravit Ratanatharathorn ◽  
Joseph P. Uberti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Locally Advanced ◽  
Standard Of Care ◽  
High Dose Chemotherapy ◽  
High Dose

e12590 Background: Adjuvant high dose chemotherapy (HDC) with Autologous Hematopoietic Stem Cell Transplantation (AuSCT) as part treatment of high risk locally advanced breast cancer has remained controversial. Multiple trials reported disease free survival (DFS) without Overall survival (OS) resulting in its abandonment in early 2000s. However, post hoc analysis of these trials consistently reported DFS and OS benefit in young and triple negative breast cancer (TNBC) subgroups. This has not been re-evaluated till date. Recent European registry reports coupled with improved transplant related mortality (TRM) and still poor out-come of standard of care in TNBC subgroup has generated renewed interest. We report long term out-come of locally advanced high risk TNBC treated with HDC and AuSCT treated in Karmanos Cancer Institute from 1995 to 2001 Methods: Majority of the patients were treated with Adriamycin and Taxane based induction chemotherapy. Patients without evidence of metastatic disease proceeded to HDC and AuSCT using Carmustine 600mg/sqm Cyclophosphamide 5.6gm/sqm and Cisplatin 165mg/sqm (STAMP 1 regimen). This is followed with loco- regional radiation per protocol. Results: 72 hormone negative patients with Lymph Node(LN) > 4 or inflammatory breast cancers were selected from 576 treated for advanced or metastatic breast cancer. 33 patients were TNB with HER2 status of 39 patients unknown. Median time from diagnosis to stem cell transplantation was 6 months. Median age at diagnosis was 47yrs. Mean LN involvement was 9 with 90% having (4-20) LN positivity. With median follow up of 16 years,10yrs DFS and OS were both 62.5%. Median follow up for DFS and OS was not reached.TRM was 9% mostly from pulmonary toxicity. Conclusions: This study of locally advanced high risk TNBC treated with adjuvant HDC and AuSCT have high 10yr OS of 62.5% compared to current standard of care. With the current improvement in TRM, reevaluation of this strategy through clinical trials in this subgroup whose outcome remain poor is reasonable.

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