Allogeneic Hematopoietic Stem Cell Transplantation for Adult AML Patients with Granulocytic Sarcoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2035-2035
Author(s):  
Hiroaki Shimizu ◽  
Takayuki Saitoh ◽  
Masatsugu Tanaka ◽  
Takehiko Mori ◽  
Nobutaka Kawai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Stem Cell Transplantation ◽  
Treatment Outcomes ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Granulocytic Sarcoma ◽  
Free Survival

Abstract Abstract 2035 Background: Recently, we described that adult AML patients with granulocytic sarcoma (GS) at diagnosis presented unique characteristics including younger age, higher WBC counts, and higher frequency of French-British-American M4 and M5 morphology than those without GS. Furthermore, GS adversely affected the relapse rate and disease free survival. However, the appropriate therapeutic strategy, especially indication of allogeneic hematopoieteic stem cell transplantation (allo-HSCT), has remained unclear. Here, we present a large-scale retrospective analysis of 503 adult AML patients who underwent allo-HSCT that compared the clinical characteristics and treatment outcomes of patients with GS to those without GS. Patients and Methods: This study included 503 consecutive adult AML patients (median age 44 (15–73), male/female; 301/202), excluding patients with acute promyelocytic leukemia, who received allo-HSCT for the first time between January 2000 and December 2008 at 9 institutions participating in the Kanto Study Group for Cell Therapy (KSGCT). GS group was consisted of patients in whom GS occurred any time in the clinical course until transplantation, such as at diagnosis, relapse, and disease progression. The c2-test was used for comparison of binary variables. The Mann-Whitney U test was used for comparison of continuous variables. overall survival (OS) and leukemia free survival (LFS) were estimated by the Kaplan-Meier method, and compared using the log-rank test. The Cox proportional hazards regression model was used for multivariate analysis of prognostic factors. P < 0.05 was considered as statistically significance. Results: Of the 503 patients, 44 patients (8.7%) had GS before transplantation. All factors including patients' characteristics and transplantation procedure were not significantly different in each group, but the patients in GS group were significantly younger (GS: median 34 years; range, 17–60 years vs. non-GS: median 46 years; range, 15–73 years; p=0.002). Treatment outcomes, GS vs. non-GS: The cumulative incidences of grade II-‡W acute GVHD, chronic GVHD, and NRM at 1 year were not significantly different in each group. The 5-year OS rate did not differ significantly between the GS and non-GS groups (47% vs. 44%, respectively; p=0.621). The 5-year LFS rate also did not differ significantly (41% vs. 38%, respectively; p=0.646). Since patients in GS group were significantly younger as mentioned above, we performed a subgroup analysis on 336 patients aged 50 or younger; 37 patients in GS group and 298 in non-GS group. Age was not significantly different between the two groups. In this subgroup, too, there was no significant difference in both the 5-year OS rate and the 5-year LFS rate. Treatment outcomes in GS group: Patients in CR at allo-HSCT achieved the significantly superior 5-year OS rate and LFS rate compared to those in non-CR, (OS: 75% vs. 24%, respectively; p=0.002), (LFS: 60% vs. 24%, respectively; p=0.046). In contrast, the prognosis of 10 patients who performed allo-HSCT with accompanying GS was dismal; 9 patients experienced a relapse within 6 months. 5-year OS rate and LFS of 8 patients, who received prior local irradiation for GS, did not significantly differ from those who did not. Both acute and chronic GVHD did not significantly affect the OS and LFS rates, respectively. Twenty-four patients (55%) experienced a relapse after allo-HSCT. Regarding the sites of relapse, only GS, only bone marrow, and both bone marrow and GS were involved in 1 patient (4%), 13 (54%), and 10 (42%), respectively. In 10 patients (91%) out of 11 with GS at relapse, GS occurred at the same site between before and after allo-HSCT. Multivariate analysis identified age and disease status as independent prognostic factors for OS. Conclusion: Patients with GS, who treated with allo-HSCT, could achieve the comparable prognosis to those without GS despite poor prognosis of GS. Notably, an excellent treatment outcome was brought about in patients received allo-HSCT in CR. This study suggests that allo-HSCT during an appropriated period may overcome this unfavorable disease. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation for Relapsed Follicular Non-Hodgkin’s Lymphoma: Single Centre Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5054-5054
Author(s):  
Amir Peyman ◽  
Stephen Couban ◽  
Kara Thompson ◽  
Louis Fernandez ◽  
Donna L. Forrest ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Grade 3

Abstract Between 1993 and 2005, 57 patients with follicular lymphoma underwent high-dose chemo/radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), 49 Allogeneic, (16 Bone Marrow and 33 Peripheral Blood), 6 MIN, 2 MUD. Median age was 47 years. Median days to neutrophil and platelet engraftment after HSCT were 18 and 13 days respectively. Twenty-five patients experienced Acute GVHD and thirty-four had Chronic GVHD (12 mild and 22 extensive). Thirty-three patients were in grade 1, 17 in grade 2, 4 in grade 3 and 3 grade 4. As of their FLIPI score, 4, 14, 21 and 18 patients were calculated to have score of 0, 1, 2 and 3 respectively. Forty-one patients are alive. Two patients have relapsed, one a year and the other two years after HSCT. The 5 year survival was 71.9% (95% CI 57.5–82.2%) and 5 year survival was 67.2% (95% CI 52.3–78.5%). Transplant related mortality rate (TRM) in 5 year was 22.4% (95% CI 63.6–86.8%). No significant differences was found among FLIPI groups 0,1,2 and 3 in terms of overall, relapse-free survival, TRM Allogeneic HSCT for patients with progressive follicular lymphoma is feasible and may result in prolonged disease-free survival.

ATG Dose Correlates with Acute and Chronic GvHD In Patients Undergoing Reduced-Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation: A Large Retrospective Monocenter Analysis on 301 Patients.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3485-3485
Author(s):  
Roberto Crocchiolo ◽  
Sabine Furst ◽  
Luca Castagna ◽  
Jean El Cheikh ◽  
Catherine Faucher ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Adult Patients ◽  
Off Label Use ◽  
Off Label ◽  
Grade 3 ◽  
Label Use

Abstract Abstract 3485 Introduction: RIC associating Fludarabine-Busulfan-ATG (FBA) is quite popular as preparative for allogeneic hematopoietic stem cell transplantation (RIC-AlloSCT). However the best association us still a matter of debate. Busulfan is crucial for disease control but limited by a dose-dependent toxicity and ATG plays a pivotal role in the prevention of both acute and chronic GvHD but with a potential higher relapse rate. Here we retrospectively compared different FBA regimens among adult patients transplanted at our Institution for a hematological malignancy, with the aim of identifying whether some pre- or peri-transplant variables are predictive of outcome. Patients and methods: on 635 patients allografted between May 1998 and Feb 2010, a total of 301 patients affected by malignancy received FBA-based RIC-AlloSCT and were the object of the present analysis. Comparisons between baseline patient, donor and AlloSCT characteristics with transplant outcome were performed: univariate and multivariate Cox regression analysis were used to find any correlation between the above mentioned variables and OS, DFS, NRM, relapse incidence, acute (aGvHD) and chronic (cGvHD) GvHD. Variables with p<0.20 were included in multivariate analysis, and only variables with a p<0.05 were retained in the final model. Results: median (range) follow-up was 917 (71-4051) days. Two-year OS, DFS and NRM were 66%, 58% and 20% for the entire cohort. Relapse at two years was 26%. Cumulative incidence of grade 2–4, grade 3–4, overall and extensive cGvHD were: 29%, 12%, 58% and 40%. In multivariate analysis, patient's age was significantly associated with OS, NRM, grade 2–4 and 3–4 aGvHD; disease status at transplant significantly correlated with DFS and relapse incidence. ATG at a dose of 5 mg/kg compared to 2.5 mg/kg, was significantly associated with a reduced risk of developing grade 3–4 aGvHD (HR= 0.46, 95% CI: 0.22–0.99, p=0.05) and cGvHD (HR= 0.33, 95% CI: 0.20–0.54, p<0.0001), without affecting relapse (p=n.s.). Overtime we modified our standard RIC from F5B2A1 (Fludarabine over 5 d, oral Bu over 2 d and ATG for1d) (N=114) to F5BX2A2 (Fludarabine over 5 d, IV Bu over 2 d and ATG over 2 d) (N=84). Population was not similar and notably older (51 vs. 57 years, p<0.0001) in the latter group. Despite this we observed similar NRM (22% vs. 23%: p=n.s.) in patients older than 55 years; in patients younger than 55 F5BX2A2 was associated with better but not statistically significant OS (77% vs. 65% at two years, p=0.21) and reduced NRM (9% vs. 18% at two years, p=0.10). Conclusions: in this large monocenter series of adult patients undergoing FBA-based RIC-AlloSCT, the use of ATG at a dose of 5 mg/kg appeared to significantly reduce incidence and severity of cGvHD and grade 3–4 aGvHD compared to ATG 2.5 mg/kg without increasing disease relapse. Moreover, despite patients' disparity between the two cohorts, reduced NRM was observed in patients < 55 years old treated with F5BX2A2 regimen with respect to those receiving F5B2A1. Disclosures: Off Label Use: Zevalin is off-label use in conditioning regimen in France.

Allogeneic Stem Cell Transplantation For Patients With Adrenoleukodystrophy. Nationwide Retrospective Study In Japan

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2148-2148
Author(s):  
Koji Kato ◽  
Hiromasa Yabe ◽  
Shunichi Kato ◽  
Souichi Adachi ◽  
Yoshiko Hashii ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Low Dose ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Transplant Outcome

Abstract Introduction Adrenoleukodystrophy (ALD) is an autosomal recessive disorder with progressive neurodegeneration caused by the mutation of ABCD1 gene and allogeneic stem cell transplantation (SCT) at its early stage is recognized as the only effective treatment modality to control the neurological symptoms. But the transplant outcome according to the conditioning regimen is not well understood so far. Here we analyzed the transplant outcome of patients with ALD using the clinical data accumulated in the Japan Society of Hematopoietic Cell Transplantation and tried to find the favorable conditioning regimen. Methods From 1988 to 2010, 76 patients with ALD were transplanted and their age at transplant was 1-34 years old (median 8). Stem cell sources the patients received were bone marrow (sibling 26, non-sibling related donor 5, unrelated volunteer donor 17), and cord blood (sibling 1, unrelated 28). Conditioning regimen was classified into four categories of A: busulfan + cyclophosphamide +/- others, (n=25), B: melphalan + total lymphoid irradiation (TLI) / thoraco-abdominal irradiation (TAI) +/- fludarabine +/- anti-thymocyte globulin (n=23), C: fludarabine + melphalan +low dose total body irradiation (TBI) (n=18), and D: others (n=10). Results Sustained engraftment was obtained in 59 patients (77.8%) and it was significantly higher in bone marrow transplant (BMT) patients than cord blood transplant (CBT) patients (87.8% vs 60.7%, P=0.001). The incidence of acute graft-versus-host disease (GVHD), chronic GVHD and treatment related mortality of all patients were 7.9%, 19.3%, and 11.9%, respectively. Ten year overall survival (OS) and event free survival (EFS) of all patients were 83.7% and 64.1%, respectively. Ten patients died of either disease progression (n=2), or transplant related complications (n=8). Five year OS and EFS according to the conditioning regimen was A: 91.6% and 75.8%, B: 85.7% and 60.9%, C: 100% and 83.3%, D: 77.8% and 48.0%, respectively and they were not significant (P=0.379 in OS and P=0.183 in EFS, respectively). TBI was given to 22 patients with median dose of 4Gy (range 2-10.2) and sustained engraftment was obtained in 19 patients and all of 22 patients are alive. In patients who were not given TBI (n=54), 41 patients obtained engraftment and 44 patients are alive. OS according to presence or absence of TBI was 100% with TBI (n=22) and 86.1% without TBI (n=54) (P=0.091). By multivariate analysis for EFS, BMT and TBI were identified as good prognostic factors compared to CBT or non-TBI (HR 3.303, P=0.005, and HR 3.257, P=0.038, respectively), but OS of CBT was improved after 2005 compared to before 2004 (94.7% vs 68.6%, P=0.090). Conclusion Our results showed that conditioning regimen which includes TBI, even at low dose could provide better transplant outcome and the result of CBT improved after 2005 even though it was proved to be a significantly poor risk factor in the analysis of entire cohort. CBT enables urgent SCT when family donor is not available, and immediate transplant is essential for patients with ALD because of its nature. More precise assessment with brain MRI and neuropsychological examination is mandatory to evaluate the transplant outcomes of patients with ALD. Disclosures: No relevant conflicts of interest to declare.

Prognostic Factors of CLL Patients Undergoing Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation in the Immunochemotherapy Era

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5865-5865
Author(s):  
Oscar B. Lahoud ◽  
Patrick Hilden ◽  
Molly A. Maloy ◽  
Parastoo B. Dahi ◽  
Hugo Castro-Malaspina ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Reduced Intensity

Abstract Background: Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative therapy for chronic lymphocytic leukemia (CLL). With this analysis we intended to identify prognostic factors in patients undergoing reduced-intensity conditioning (RIC) or non-myeloablative (NMA) HCT at our center in the immunochemotherapy era. Methods: This retrospective chart review included all CLL patients who underwent RIC or NMA conditioned HCT at Memorial Sloan Kettering Cancer Center (MSKCC) in the immunochemotherapy era between 09/2006 and 10/2014. We then analyzed whether pre-HCT factors including age, disease response status at the time of HCT, presence of Richter's transformation, 17p deletion or TP53 mutation, use of anti-thymocyte globulin (ATG), number of prior lines of treatment, and time from diagnosis to HCT, were associated with overall survival (OS), progression-free survival (PFS), non-progression mortality, and grade 2-4 acute graft versus host disease (aGVHD). Univariate factors were evaluated via log-rank or Gray's test as appropriate, while Cox regression models were used to explore the adjusted effect of multiple factors. Results: Thirty-five patients undergoing RIC or NMA HCT with a median age of 53 years (range 36.3-69.0) were analyzed. The patients had a median of 4 prior lines of therapy (range 1-10) and a median time from diagnosis to HCT of 65.8 months (range 7.5-159.0). With a median follow-up for survivors of 58.8 months (95% CI 17.0-NA), the 5-year PFS and OS were 32.4% (95% CI 17.4-48.4) and 49.4% (95% CI 31.2-65.2), respectively (Figure 1). Treatment-related mortality was 20.0% (95% CI 8.7-34.7) and 31.8% (95% CI 17.0-47.6) at 1 and 2 years, respectively. Chemosensitive disease, defined by complete or partial remission per contemporary International Workshop CLL (iwCLL) response criteria at the time of HCT, was associated with improved 3-year OS of 68.0% (95% CI 46.1-82.5) compared to patients with chemorefractory disease to last line of therapy (stable or progressive disease) with a 3-year OS of 15.0% (95% CI: 1.0-45.7, p = 0.002, Figure 2). Additionally, patients with ≤4 lines of therapy prior to HCT experienced superior 5-year OS of 61.2% (95% CI 37.5-78.2) contrasted to 20.0% (95% CI: 3.1-47.5) in patients with >4 prior lines of therapy (p = 0.008, Figure 3). This difference approached statistical significance in multivariate analysis (HR 2.43, 95% CI 0.91-6.50; p = 0.076) adjusted for chemosensitivity. Furthermore, when adjusted for the number of prior lines of therapy, chemorefractory patients remained at greater risk of death in multivariate analysis (HR 3.29, 95% CI: 1.14-9.48, p = 0.027). Other factors including: age, history of transformed disease, the presence of 17p or TP53 deletion/mutation, time from diagnosis to HCT, or use of ATG with NMA/RIC did not impact PFS or OS. Conclusion: This is the first study to report independent prognostic impact of the number of lines of therapy prior to NMA/RIC HCT on OS for CLL patients in the post-immunochemotherapy era. We confer findings from other groups including: the prognostic significance of chemosensitivity at the time of HCT as well as HCT overcoming poor-risk cytogenetics associated with 17p chromosomal aberrations. Our data is limited by lack of patients previously exposed to recently FDA approved novel kinase or BCL2 inhibitors. Nevertheless, given our reported data, HCT should still be considered as the only therapy with curative potential for poor-risk patients earlier in their disease course, while chemosensitivity is maintained and prior to the accumulation of multiple lines of therapies. Disclosures Perales: Incyte Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Unrelated stem cell transplantation in multiple myeloma after a reduced-intensity conditioning with pretransplantation antithymocyte globulin is highly effective with low transplantation-related mortality

Blood ◽  
2002 ◽  
Vol 100 (12) ◽  
pp. 3919-3924 ◽  
Author(s):  
Nicolaus Kröger ◽  
Herbert Gottfried Sayer ◽  
Rainer Schwerdtfeger ◽  
Michael Kiehl ◽  
Arnon Nagler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Antithymocyte Globulin ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Reduced Intensity

We investigated the feasibility of unrelated stem cell transplantation in 21 patients with advanced stage II/III multiple myeloma after a reduced-intensity conditioning regimen consisting of fludarabine (150 mg/m2), melphalan (100-140 mg/m2), and antithymocyte globulin (ATG; 10 mg/kg on 3 days). The median patient age was 50 years (range, 32-61 years). All patients had received at least one prior autologous transplantation, in 9 cases as part of an autologous-allogeneic tandem protocol. No graft failure was observed. At day 40 complete donor chimerism was detected in all patients. Grade II to IV acute graft-versus-host disease (GVHD) was seen in 8 patients (38%), and severe grade III/IV GVHD was observed in 4 patients (19%). Six patients (37%) developed chronic GVHD, but only 2 patients (12%) experienced extensive chronic GVHD. The estimated probability of nonrelapse mortality at day 100 was 10% and at 1 year was 26%. After allografting, 40% of the patients achieved a complete remission, and 50% achieved a partial remission, resulting in an overall response rate of 90%. After a median follow-up of 13 months, the 2-year estimated overall and progression-free survival rates are 74% (95% CI, 54%-94%) and 53% (95% CI, 29%-87%), respectively. A shorter progression-free survival was seen in patients who already experienced relapse to prior autograft (26% versus 86%, P = .04). Dose-reduced conditioning with pretransplantation ATG followed by unrelated stem cell transplantation provides durable engraftment and donor chimerism, reduces substantially the risk of transplant-related organ toxicity, and induces high remission rates.

Hyperlipidemia After Allogeneic Stem Cell Transplantation: Prevalence, Risk Factors and Impact on Prognosis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3458-3458
Author(s):  
Yuki Kagoya ◽  
Sachiko Seo ◽  
Yasuhito Nannya ◽  
Mineo Kurokawa
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Calcineurin Inhibitors

Abstract Abstract 3458 Introduction: Hyperlipidemia is one of the late complications after allogeneic stem cell transplantation (SCT). Although intrahepatic cholestasis caused by chronic graft-versus host disease (GVHD) or calcineurin inhibitors has been considered to be one of the etiologies, its prevalence, risk factors, and the impact on prognosis have not been investigated well. Methods: We performed a retrospective analysis of 194 adult patients who underwent allogeneic SCT between 1995 and 2008 in our institute, and survived more than 100 days after SCT. Hypercholesterolemia or hypertriglyceridemia was defined as more than 240 mg/dl or 200 mg/dl, respectively, at two successive tests at least one week apart after the first 100 days after SCT. Cumulative incidence of hypercholesterolemia or hypertriglyceridemia was analyzed. The time to the development of hypercholesterolemia or hypertriglyceridemia was calculated and the multivariate analysis of pre- and posttransplant variables was performed by a Cox proportional hazards model. Chonic GVHD, chronic liver dysfunction (CLD; defined as more than twice the upper limit of normal for aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase, or total bilirubin >3 mg/dl over 3 months) and administration of calcineurin inhibitors were studied as posttransplant factors, which were assessed as time-dependent variables. To analyze the prognosis of patients who developed persistent hyperlipidemia, the multivariate analysis of overall survival (OS), relapse rate, and non-relapse mortality (NRM) was carried out by a landmark approach. Persistent hyperlipidemia was defined as hypercholesterolemia or hypertriglyceridemia continuing more than 3 months. Results: Overall, 83 (42.8%) and 98 (50.5%) patients developed hypercholesterolemia and hypertriglyceridemia, respectively. The median follow-up period of serum cholesterol and triglyceride values in surviving patients was 44 months. The cumulative incidence of each abnormality at 3 years after SCT was 38.1% (95% confidence interval [CI]: 31.0–45.1%), and 46.0% (95% CI: 38.8–52.9%), respectively. In a multivariate analysis, the development of chronic GVHD was independently associated with both hypercholesterolemia (hazard ratio [HR] 2.05, 95% CI: 1.23–3.43, P<0.01) and hypertriglyceridemia (HR 2.04, 95% CI: 1.30–3.18, P<0.01). Besides, CLD was significantly associated with hypercholesterolemia (HR 2.20, 95% CI: 1.39–2.50, P<0.01). Administration of calcineurin inhibitors was not an independent risk factor for the development of hypercholesterolemia (HR 1.23, 95% CI: 0.73–2.08, P=0.43) or hypertriglyceridemia (HR 1.03, 95% CI: 0.61–1.54, P=0.89). Among pretransplant factors, prior hypercholesterolemia and hypertriglyceridemia were associated with posttransplant hypercholesterolemia (HR 2.76, 95% CI: 1.07–7.17, P=0.04) and hypertriglyceridemia (HR 2.04, 95% CI: 1.27–3.27, P<0.01), respectively. Persistent hyperlipidemia was found in 49 patients (25.3%), of which 35 patients (71.4%) developed hyperlipidemia within one year. The median interval to the occurrence of hyperlipidemia of the patients was 180 days after SCT. In univariate analysis, patients with persistent hyperlipidemia had a tendency of better 3-year OS (77.3% vs 64.7%, P=0.23). Multivariate analysis showed that the development of persistent hyperlipidemia was independently associated with better OS (HR: 0.49, P=0.049). Further, although not statistically significant, patients with persistent hyperlipidemia had a tendency of lower 3-year cumulative relapse rate (15.7% vs 20.3%). There were no significant differences in 3-year NRM between patients with or without hyperlipidemia (12.3% vs 13.9%). Conclusions: Both hypercholesterolemia and hypertriglyceridemia are very common complications after SCT. Patients with persistent hyperlipidemia, however, have significantly better OS. Considering a strong association between the development of hyperlipidemia and chronic GVHD, and a tendency of lower relapse rate in patients with persistent hyperlipidemia, hyperlipidemia is regarded as one of the symptoms accompanied with chronic GVHD. Unless severe, its incidence indicates a better control of the primary disease and an improved prognosis. Disclosures: No relevant conflicts of interest to declare.

Autologous Hematopoetic Stem Cell Transplantation as An Intensive Consolidation Therapy for Adult Patients in Remission from Acute Myeloid Leukemia.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4595-4595
Author(s):  
Sonja G Genadieva-Stavrik ◽  
Alexandra Pivkova ◽  
Zlate Stojanoski ◽  
Svetlana Krstevska-Balkanov ◽  
Borce Georgievski
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Transplantation ◽  
Allogeneic Bone ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Stem Cell Source

Abstract Abstract 4595 Despite advances in our understanding of its pathogenesis, acute myeloblastic leukemia remains difficult to treat. Although initial complete remission can be achieved in a high percentage of patients, relapse occurs in 70–80% of the patients. Two main approaches have been the attempt to eradicate the leukemic clonal cells population via chemotherapy with or without autologous stem cell rescue or to pursue a combined approach using an antileukemic therapy combined with an antileukemic immune response via allogeneic bone marrow transplantation. Autologous transplantation compares favorably against allogeneic bone marrow transplant in several ways. Autologous transplantation can be used as a consolidation therapy in the older population, and lack of a matched donor does not preclude the patients from this treatment. We report a retrospective analysis on 48 patients diagnosed with de novo AML, who did not have an available histocompatible donor, and who underwent autologous transplantation between years 2000–2009 at the University hematology Clinic, Skopje, Macedonia. All patients had ECOG score 1 or less. The patient's age ranged from 17 to 65 years with the median age 41 years. There were 26 males and 22 females. For stem cell mobilization patients received chemotherapy or chemotherapy plus G-CSF. The preparative chemotherapy regimen prior to autologous transplantation consisted of BuCy in 24 patient, BEAM in 22 and BuCyMel was used in the remaining 2 patients. We used bone marrow as primary source of stem cells in 18 patients, and peripheral blood stem cells in remaining 30 patients. The five years overall survival was 52% and the 5 years disease progression free survival were 42%. We analyzed sever factors that can influence the overall survival and the disease free survival such as: age, disease status, stem cell source, chemotherapy regiments prior to transplantation, conditioning regiments, number of mobilized stem cells. Advanced age and bone marrow stem cell source seems to be more influent factors. We report that the clinical results of autologous hematopoietic stem cell transplantation are sufficiently encouraging to warrant future trials that include autologous transplantation as an option for appropriately selected patients with AML in CR1. We conclude that autologous hematopoietic stem cell transplantation is a reasonable and save intensive consolidation for patients with acute myeloblastic leukemia who do not have a suitable HLA–matched donor. Disclosures: No relevant conflicts of interest to declare.

The Impact of ATG/Alg in Preconditioning On the Allogeneic Stem Cell Transplantation for Patients with Acute Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4185-4185
Author(s):  
Koji Kato ◽  
Yoshiko Atsuta ◽  
Kazuteru Ohashi ◽  
Takahiro Fukuda ◽  
Shuichi Taniguchi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Cell Sources ◽  
The Impact

Abstract Abstract 4185 Background: Since the clinical implication of anti-lymphocyte globulin (ATG/ALG) in allogeneic stem cell transplantation (allo-SCT) is not fully understood, we tried to identify the clinical impact of ATG/ALG in patients with acute leukemia who received allo-SCT in Japan. Patients and Methods: We analyzed patients with ALL (n=5494) and AML (n=8115) who received first allogeneic SCT from 1983 to 2009 with (n=356) or without (n=13253) ATG/ALG. Their stem cell sources were bone marrow (BM, n=9056), peripheral blood (PB, n=1918), and cord blood (CB, n=2575) and they were transplanted at 1st complete remission (CR1, n=5681), 2nd CR (CR2, n=2495), and advanced stages (>CR3, n=5033). Results: Five year overall survival (5y OS) of all patients with or without ATG/ALG was 33.6% vs 44.5%, respectively (P<0.001) and multivariate analysis showed that ATG/ALG significantly reduced acute GVHD (P<0.001, HR=1.980) as well as chronic GVHD (P<0.001, HR=1.894). According to stem cell sources, 5y OS with or without ATG/ALG was 35.8% vs 47.5% (P<0.001) in BM, 34.7% vs 37.6% (P=0.067) in PB and 18.3% vs 39.9% (P<0.001) in CB. By multivariate analysis, ATG/ALG significantly reduced A-GVHD (P=0.005, HR=1.565) but decreased OS (P=0.004, HR=0.729) in BM, it reduced A-GVHD (P<0.001, HR=2.376) and C-GVHD (P<0.001, HR=2.691) but lowered engraftment (P=0.046, HR=0.810) in PB, and it increased TRM (P=0.004, HR=0.437) with decreased OS (P=0.011, HR=0.576) in CB. In Haplo transplantation (SCT from 2 or 3 antigens of HLA mismatched family donor, n=337), multivariate analysis showed that ATG/ALG did not affect the relapse, TRM and OS but, it significantly lowered engraftment (P=0.002, HR=0.602), and reduced A-GVHD (P<0.001, HR=2.622) as well as C-GVHD (P<0.001, HR=3.834). In contrast to these results, ATG/ALG did not affect the relapse rate irrespective of stem cell source or diagnosis. Conclusion: In allogeneic stem cell transplantation for patients with ALL and AML, ATG/ALG contribute in reducing acute and chronic GVHD without affecting relapse rates but it was a risk factor of OS for patients who received BM or CB. Disclosures: No relevant conflicts of interest to declare.

Clinical Impact of Additional Cytogenetic Aberrations and Treatment in Pediatric t(8;21)-Positive AML: Results from an International Retrospective I-BFM-SG Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 884-884
Author(s):  
Ardine Reedijk ◽  
Gertjan Kaspers ◽  
Marta Fiocco ◽  
Andrea Pession ◽  
Dirk Reinhardt ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Low Dose ◽  
Male Gender ◽  
Chromosome 4 ◽  
Factors Associated ◽  
Significant Factors

Abstract Abstract 884 Core binding factor AML is generally considered to have a favorable prognosis, but in several studies, patients with a t(8;21)(q22;q22) RUNX1/RUNX1T1 have relapse rates greater than 30%. Factors that reliably discriminate between pediatric AML patients with t(8;21) who remain in remission and those who relapse have not yet been described. In this study, we aim to identify markers that are present at diagnosis, predict clinical outcome, and may be useful for risk stratification and/or risk-adapted therapy. From 19 childhood cancer study groups worldwide, we collected data from 916 patients with de novo AML positive for t(8;21) and/or AML1-ETO fusion gene enrolled from 1987 to 2010. All complete karyotypes (n=838) were centrally reviewed and classified according to type and number of aberrations. Recurrent aberrations (occurring in at least 10 patients) were considered for statistical analysis. These aberrations included deletion of one sex chromosome, del(9q), abnormality of 7q, trisomy 4 and trisomy 8. Patients were also subdivided according to the number of abnormalities in association with t(8;21). Achievement of complete remission (CR), 5 year (y) overall survival (OS), 5y event-free survival (EFS) and cumulative incidence of relapse (CIR) were analysed for all potential prognostic factors, and regarding treatment for anthracyclines and allogenic stem cell transplantation. All variables significant at the 0.1 level in univariate analysis were entered into a multivariable Cox proportional hazards regression model. Variables were removed if they were not significant at the level of 0.05 on the basis of the likelihood ratio test. The 838 patients with complete karyotypes had a CR-rate, 5y OS, EFS and CIR of 92.5%, 74.2% (95%CI 71.5–76.6), 59.8% (95%CI 56.5–62.9) and 28.1% (95%CI 24.9–31.3), respectively. In total 229 patients died; including 37 who did not achieve CR, 125 after relapse and 67 in remission during or after treatment. Clinical features and treatment related factors significantly associated with inferior OS were age > 15 y, male gender, WBC ≥20×109/L, low dose anthracyclines in induction (≤150mg/m2 in the first course of chemotherapy) and gain of chromosome 4. In multivariate analysis, age (15+ vs. 0–4 years HR = 2.27 (95% CI 1.42–3.63), p=0.001), high WBC (HR = 1.56 (95%CI 1.20–2.04), p=0.001), and gain of chromosome 4 (HR = 2.70 (95%CI 1.52–4.79) p = 0.001) remained significant. Factors associated with inferior EFS were male gender, WBC ≥20×109/L, CNS involvement, percentage of blasts <60 % in bone marrow at diagnosis, low dose anthracyclines in induction (≤150mg/m2) and gain of chromosome 4. In multivariate analysis, high WBC (HR = 1.51 (95%CI 1.19–1.91), p= 0.001), low dose anthracyclines in induction (HR = 1.33 (95%CI 1.04–1.71), p = 0.021) and gain of chromosome 4 (HR = 2.84 (95%CI 1.67–4.80), p < 0.001) were significant. Factors associated with higher CIR were high WBC (HR = 1.50 (95%CI 1.13–2.00), p= 0.006), low dose anthracyclines in induction (HR = 1.42 (95%CI 1.03–1.97), p = 0.034), gain of chromosome 4 (HR = 2.31 (95%CI 1.21–4.39), p= 0.011) and no allogeneic stem cell transplantation in first CR (HR = 2.58 (95%CI 1.51–4.39, p < 0.001). In conclusion, this is the largest pediatric cohort of t(8;21)-positive AML described to date, with several new findings. Apart from the well known prognostic factors: age and WBC at initial diagnosis, we found that patients who received more than 150 mg/m2 of anthracyclines in induction had a lower CIR, and a better EFS and OS. Regarding karyotype, the presence of additional aberrations per se did not impact on outcome. However, in relation to particular additional aberrations, gain of chromosome 4 was associated with a three-fold higher risk of relapse. Disclosures: No relevant conflicts of interest to declare.

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