Evaluation of Enteral Versus Parenteral Feeding As Nutritional Support In Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4576-4576
Author(s):  
Richard Lemal ◽  
Romain Guièze ◽  
Cécile Moluçon-Chabrot ◽  
Eric Hermet ◽  
Aurélie Ravinet ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Duration ◽  
Nutritional Support ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Early Outcome ◽  
Transfusion Requirements ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4576 Introduction Allo-HSCT procedure is associated with a frequent and potentially severe malnutrition which could highly participate to the transplant-related morbidity (TRM). Optimal nutritional management is still poorly known while both enteral nutrition (EN) and parenteral nutrition (PN) are effective. We proposed to retrospectively evaluate the impact of EN versus PN as nutritional support on early outcome of allo-HSCT. Patients and methods We retrospectively analyzed all the successive patients who needed a nutritional support during their first allo-HSCT in our center from January 2009 to October 2010, excepting whose who had a progressive disease at time of transplant. Datas were compared in an intent to treat analysis according the EN or PN initial nutritional support strategy. Results We analysed early outcome of 56 successive patients. Twenty of them received a myeloablative conditioning regimen and 36 a reduced intensity one. A total of 28 agreed to receive EN via a nasogastric feeding tube and the remaining 28 received PN. No significant difference in terms of age, diagnosis, disease status at transplant, conditioning regimens, stem cell source, GVHD nor antifungal secondary prophylaxis could be observed between the EN and PN groups. We found a lower median duration of fever in EN (2[0–8] vs. 5[0–17] (days); p=0.0026) and a lower need for antifungal therapy in EN group (7/28 vs. 17/28; p=0.0069), with a lower median duration of intravenous antifungal use (0 day [0–99] in EN vs. 7 days [0–93] in PN; p=0.00034) while incidence of bacteriemiae was not different. We observed a lower rate of replacement of central veinous catheter in EN group (3/28 in EN vs. 9/28 in PN; p=0.05) and a lower rate of transfer to ICU in the EN group (2/28 in EN vs. 8/28 in PN, p=0.036) but early death rate (<100 days) was the same in each group (4/28 vs. 4/28, p=NS). Median neutropenia and thrombopenia duration and median transfusion requirements were not significantly different. Fourteen patients in EN group and 18 in PN group presented a grade 3–4 oral mucositis (p=NS). Grade III-IV GVHD incidence was comparable in both groups (4/28 vs. 8/28; p=0.19). Conclusion Compared with PN, EN directly decreases the infectious risk, particularly the fungal risk, and its complications in allo-HSCT, without influencing hematopoietic toxicity nor GVHD incidence. Based on these encouraging results, we are now conducting a prospective, multicentric and randomized trial to confirm EN benefice in allo-HSCT. Disclosures: No relevant conflicts of interest to declare.

Alpha-Catenin Is Dispensable for Normal Hematopoietic Stem Cell Function.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1438-1438
Author(s):  
Natallia Mikhalkevich ◽  
Michael W. Becker
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Conflicts Of Interest ◽  
Fusion Product ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
Myeloid Neoplasms ◽  
Increased Risk ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 1438 Poster Board I-461 We previously demonstrated the loss of expression of alpha-E-Catenin, the product of the CTNNA1 gene, in primary leukemic stem cells isolated from patients with advanced Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) associated with loss of all or part of the long arm of chromosome 5. To formally assess the impact of loss of Ctnna1 expression on hematopoiesis, we employed a murine model for the hematopoietic specific conditional loss of Ctnna1 expression. We demonstrate that Ctnna1 deficiency is associated with normal hematopoietic maturation and proliferation as assessed by peripheral blood examination and methycellulose colony assays. We assessed stem cell and early progenitor frequencies using both flow cytometry and functional assays. Ctnna1 deficiency was associated with equivalent frequencies of Sca1+C-Kit+CD135-Lineage- HSCs in both experimental animals and controls. Short term HSC and MPP frequencies were likewise unaltered. We assessed HSC function using transplantation studies. In competitive repopulation experiments, HSCs deficient for Ctnna1 maintained stable engraftment of recipient mice for up to 1 year. Limiting dilution analyses detected no significant difference in HSC frequency between wild type and Ctnna1 deficient mice. We examined the potential role of Ctnna1 deficient hematopoietic stem cells in two murine models for myeloid neoplasms 1.) exposure to mutagen ENU and 2.) a model for murine AML driven by the HoxA9-Nup98 fusion product. Following exposure of HSCs to ENU, loss of Ctnna1 was not associated with an increased risk of development of a myeloid neoplasm. Expression of the HoxA9-Nup98 fusion product by retroviral infection of Ctnna1 deficient and wild type Sca1+C-Kit+Lineage- cells resulted in no difference in time to development of the previously characterized myeloproliferative disorder or acute leukemia. Taken together, these data demonstrate that in the absence of specific genetic abnormalities, loss of Ctnna1 expression in primary murine HSCs is not associated with aberrant HSC function or the development of myeloid neoplasms. Further studies are necessary to define a role for of loss of Ctnna1 expression in human myeloid malignancies. Disclosures No relevant conflicts of interest to declare.

Antithymocyte Globuline Given as Part of the Conditioning Regimen Has No Impact On Lung Function at 1 Year After Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3306-3306
Author(s):  
Filippo Milano ◽  
Margaret A. Au ◽  
H. J. Deeg ◽  
Jason Chien
Keyword(s):  
Stem Cell ◽  
Lung Function ◽  
Pulmonary Function ◽  
Retrospective Analysis ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Lung Dysfunction ◽  
Significant Difference ◽  
The Mean ◽  
The Impact

Abstract Abstract 3306 Poster Board III-194 Background Pulmonary dysfunction is common following allogeneic hematopoietic stem cell transplantation (HSCT) and is associated with significant morbidity and mortality. The use of Antithymocyte globuline (ATG) has reduced the incidence of graft versus host disease (GVHD), particularly in its chronic form, but the impact of this approach on the prevention of lung dysfunction is not well characterized. Methods We performed a retrospective analysis of pulmonary function in all patients transplanted from January 2001 through December 2005 following conditioning with oral busulfan (BU) followed by either cyclophosphamide (CY) or fludarabine (FLU) with or without the addition of ATG. Pulmonary function tests (PFTs) were performed per transplant protocol before and around day 80 and 1 year after transplantation. Results Of 406 patients, 13 (3%) were excluded due to lack of pre-transplant PFTs. Seventy five patients received ATG (thymoglobulin, given on days -3 to -1 for total doses of 4.5 – 6 mg/kg), and 318 did not. The median patient age was 49 years for both the ATG (range 9-65) and non-ATG (range 7-66) groups; the median follow-up was 956 (range 19-2071) days and 903 (range 8-2697) days, respectively. The ATG group had proportionally more patients with high risk diseases (62.7% vs 45.7%, p= .03), whereas the use of bone marrow as stem cell source was higher in the non-ATG group (14.6% vs 5.3%, p=.03). The proportion of patients with PFTs at 1 year was similar for both groups (49.3% vs 54.6%, p=.55). No significant statistical differences between the 2 groups were seen in the mean percentage of the predicted values for FEV1, FVC, TLC and DLco at 80 days or 1 year after transplantation. The mean value of FEV1/FVC ratio at 1 year was higher for ATG patients (0.81±0.05 vs 0.77±0.09, p=.003). The mean change in PFT parameters from baseline to 1 year after HSCT also did not show a statistically significant difference between the 2 groups for any PFT parameters except for the FEV1/FVC ratio, which decline was lower in the ATG group (0.4±3.9 vs -2.8±7.3 p=.0002). This difference remained significant in multivariate analysis. The lung function score at 1 year after transplantation was similar in the 2 groups; they also had similar rates of lung function decline (expressed as the annualized rate of FEV1 decline) from baseline to 1 year after HSCT. The risk of developing severe airflow obstruction (AFO) or a restrictive pattern (RP), as well as the cumulative incidence of AFO and RP were not statistically significantly different between the 2 treatment groups at 1 year after HSCT. Conclusions In this retrospective analysis, incorporation of ATG into the HSCT conditioning regimen did not appear to be associated with superior outcome in terms of post transplant pulmonary function. However, further evaluations are needed to better clarify the role that ATG might have in the development of late-term pulmonary complications. Disclosures No relevant conflicts of interest to declare.

Is Not Age, But Comorbidities. Allogeneic Hematopoietic Stem Cell Transplantation In Patients Older Than 50 Years In Argentina

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5467-5467
Author(s):  
Mariano Berro ◽  
Juan Garcia ◽  
Ana Basquiera ◽  
Maria Marta Rivas ◽  
Maria Cecilia Foncuberta ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Transplant Outcome ◽  
Significant Difference

Abstract Materials and Methods We retrospectively reviewed 137 medical records of patients older than 50 years receiving an allogeneic hematopoietic stem cell transplant (HSCT) in 9 centers from Argentina. We evaluated the following characteristics: sex, age, diagnosis, stage, comorbidities (according to the HCT-CI score), type of donor, histocompatibility, source, conditioning and immunosupression. We analyzed the incidence and severity of acute Graft-vs-Host disease (aGVHD) with Chi Square, Overall Survival (OS) and Disease Free Survival (DFS) with Kaplan Meier and Relapse, Non Relapse Mortality y chronic GVHD (cGVHD) with CI. For multivariate analysis (MA) we included variables that in univariate had a p<0.2, used Cox regression model for time dependant outcomes and logistic regression for dichotomic variables, considering significant a p<0.05. Results Patients characteristics are listed in table 1. Between January 1997 and July 2013, 137 transplants were performed in adults older than 50 years, with a median follow up 1.3 years. Acute GVHD incidence was 41% (19% were grade II and 7.3% III-IV). The only variable associated with aGVH clinically significant (G II-IV) was AML that was protective (14% vs 35%, p<0.01; significant in MA, HR 0.29; 95% CI 0.12-0.72). Chronic GVHD incidence was 25%, extensive in 9.4% and the only risk factor for this outcome was MPN (1-3 years 40%-NA vs 12-20%, p=<0.01). Global OS 1 and 3 years was 44 and 20%, DFS was 33 and 20%, Relapse was 35 and 41% and NRM was 36 and 43% respectively. Co-morbid patients showed a significant increase in NRM (HCT.CI 0 vs 1 vs ≥2, 1-3 years 17-24%, 40-46% and 45-67%, p=0.01; significant in MA, for HCT.CI 0 vs ≥1, HR 2.4, 95% CI 1.12-5.25), as well as male patients (1-3 years 36-47% vs 23-27%, p=0.03), MPN (1-3 years 43-65% vs 29.34%, p=0.01) and Cyclosporine based immunosuppressant regimen (CSA) vs tacrolimus (1-3 years 47-53% vs 25-36%, p=0.01). AML patients experienced a higher relapse rate (1-3 years 50-50% vs 28-32%, p<0.01) as well as Fludarabine-Busulfan conditioning (1-3 years 45-48% vs 31-32%, p=0.02). Finally patients without comorbidities (HCT.CI 0 vs ≥1) had higher OS (1-3 years 54-30% vs 36-16%, p=0.03) and DFS (1-3 years 43-31% vs 30-15%, p=0.05) as well as tacrolimus vs CSA base regimen that had higher OS (1-3 years 49-25% vs 31-13%, p=0.01) and DFS (1-3 year 41-26% vs 20-11%, p<0.01; significant in MA, HR 0.56, 95% CI 0.33-0.98). Age (older than 60 vs younger), type of donor, use of myeloablative conditioning regimen and source did not showed any significant difference in the outcome analyzed. Conclusion HSCT is a valid therapeutic option for older patients. In this retrospective analysis of patients older than 50 years, we found that the main risk factors that impact in transplant outcome are patients comorbidities and not age, whereas transplant related toxicities increase with the number of comorbidities and therefore decrease OS and DFS. Beyond the fact that certain disease experienced more aGHVD (AML) or cGVHD and higher NRL (MPN) the other factor significantly related in transplant outcome was the use of tacrolimus vs CSA. Disclosures: No relevant conflicts of interest to declare.

The Impact of Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents with Recurring Hodgkin’s Lymphoma: An EBMT Study on 151 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3061-3061 ◽  
Author(s):  
Alexander Claviez ◽  
Carmen Canals ◽  
Marc Boogaerts ◽  
Jerry Stein ◽  
Stephen Mackinnon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Performance Status ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
The Impact ◽  
Time Point

Abstract Background: Allogeneic hematopoietic stem cell transplantation (HSCT) has become a therapeutic option for patients with recurring Hodgkin’s lymphoma (HL). Standardized inclusion criteria, the optimal time point and the type of conditioning regimen have, however, not been clarified yet. Moreover, high treatment related mortality (TRM) has hampered the widespread use of this procedure. Only few data are available on the impact of allogeneic HSCT in pediatric and adolescent patients. Patients and Methods: We analyzed patients registered in the EBMT Lymphoma Database (age < 21 years at transplantation) who received an allogeneic HSCT for relapsed or refractory HL between 1987 and 2005. Results: A total of 151 patients (56% male) were included. Median age at diagnosis and HSCT was 15 and 18 years, respectively. 57% of patients had received three or more lines of treatment prior to allogeneic HSCT including autologous HSCT in 77 patients with a median interval of 18 months between autologous and allogeneic HSCT. The majority of donors were matched related (63%), followed by matched unrelated (25%) and mismatched donors. A full myeloablative conditioning regimen was given to 40% of patients and 60% received a regimen of reduced intensity. Disease status at HSCT was sensitive (complete or partial remission) in 59% and refractory (no change or progression) in 41%. 23% of the patients developed grade 2–4 acute graft versus host disease (GvHD). Of 35 patients with evaluable chronic GvHD, limited and extensive GvHD were balanced. With a median follow-up of 25 months (maximum 154), 75 patients (50%) are alive and 59 of them disease-free. 56 patients (37%) relapsed after a median time of 5 months (<1 to 36 months) and only 16 were alive at last contact. The probability for progression-free survival (PFS) at 2 and 5 years were 39% and 29% respectively. The cumulative incidences (CI) for relapse at 1, 2 and 5 years were 29%, 37% and 44%, respectively, whereas the CI for TRM at 1, 2 and 5 years were 20%, 24% and 27%, respectively. In multivariate analysis, HLA disparity (p=.002), HSCT before 2001 (p=.01) and female sex (p=.02) were associated with a higher TRM, while poor performance status (p=.005) and refractory disease (p=.04) resulted in an inferior PFS. Reduced treatment intensity had no impact on relapse rate within one year after HSCT but was associated with a higher incidence of relapse (p=.02) beyond 12 months. The PFS and TRM of patients without adverse prognostic factors (HSCT >2001, matched donors and good performance status at HSCT) at 1, 2 and 5 years was 67%, 50% and 43%, and 11%, 17% and 17%, respectively. Conclusion: This study of young patients with HL receiving allogeneic HSCT indicates a comparable outcome to adult patients. Transplantation was beneficial especially for patients with a good performance status, HSCT in recent years and available matched donors. Allogeneic HSCT should be carefully selected at an early time point in children failing standardized primary and salvage treatment.

Long-Term Clinical Outcome of Children with Acquired Aplastic Anemia in Brazil.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4216-4216
Author(s):  
Marlene Pereira Garanito ◽  
Vicente Odone Filho ◽  
Marcela Vieira dos Santos ◽  
Elvira Velloso ◽  
Frederico L. Dulley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Cell Transplantation ◽  
Survival Probability ◽  
Conflicts Of Interest ◽  
Time History ◽  
Hematopoietic Stem ◽  
Significant Difference

Abstract Abstract 4216 Introdution/ Backgound Acquired Aplastic Anemia (AAA) is a rare hematologic disorder characterized by pancytopenia and hypocelular bone marrow. The pathophysiology is immune mediated in most cases. Environmental exposures to drugs, viruses and toxins, are thought to trigger the aberrant immune response in some patients. However, 50 to 74 percent of cases are classified as idiopathic. The highest frequency occurs in young population (15 to 25 years) with a second peak at age of 65 to 69 years. Immunosuppressive therapy is the best treatment in children with AAA who do not have a suitable donor for allogeneic stem cell transplantation. Materials and methods We reviewed the medical records of patients diagnosed with severe (SAA) and very severe acquired aplastic anemia (vSAA) at the Department of Pediatrics, Instituto da Criança – Hospital das Clínicas, University of Sào Paulo, Brazil from December, 1992 to December, 2007. We analyzed the clinical characteristics of the patients at diagnosis and the response to immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT). Results In this study, 47 patients (27 boys and 20 girls), younger than 16 years, were diagnosed with vSAA (n= 21) or SAA (n=26). The median age was 7,71 years, ranging from 0.5 to 16 years and the average time history (beginning of signs and symptoms related to the disease and diagnosis) of the disease was 4,82 months, ranging from 0,25 to 48 months. Of the 47 patients, 45 had idiopathic AAA and 2 had hepatitis-associated. The median follow-up was 6,91 years for the patients treated with IST and 3,10 years for the patients who underwent to HSCT. One patient died before any treatment. For the eight patients who underwent to allogenic HLA-matched HSCT the 5-years-survival probability was 50%. For the 38 patients treated with IST, ten of them received cyclosporine and a short course of corticosteroids (CsA/CE) and 28 received antithymocyte globulin plus cyclosporine (ATG/CSA). The 5 years survival probability was 40% and 55%, respectively (p:0,0054). According to the severity of AAA, we did not show a significant difference in survival (p:0,32). Eight patients received second treatment after 1 year and 6 months (6 ATG from different species and CsA, 1 CsA and 1 thalidomide) and the probably of survival at 5 years was 60%. Among the 18 patients who responded to IST, four relapsed (22%). Two patients developed acute myeloid leukemia at 5 and 12 years after diagnosis. Conclusion Our results both for patients undergoing HSCT, as well as patients undergoing IST are lower in comparison to other hematological centers. Probably, this discrepancy is related to the prolonged time of disease when patients are admitted to our service. Unfortunately, the difficulty of access to specialized centers for diagnosis and early treatment in our country is a reality and this fact contributes to the delay to the beginning of treatment. Disclosures: No relevant conflicts of interest to declare.

Cytogenetic Evolution (CE) In Patients (pts) with Low and Intermediate Risk Myelodysplastic Syndromes (MDS) Is Associated with Poor Prognosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2941-2941
Author(s):  
Liunan Li ◽  
Elias Jabbour ◽  
Gautam Borthakur ◽  
Stefan Faderl ◽  
Tapan Kadia ◽  
...  
Keyword(s):  
Disease Progression ◽  
Cytogenetic Analysis ◽  
Conflicts Of Interest ◽  
Myelogenous Leukemia ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Significant Difference ◽  
The Impact ◽  
Cytogenetic Evolution

Abstract Abstract 2941 Introduction: MDS is a spectrum of abnormalities in the proliferation and differentiation of hematopoietic stem cells that result in peripheral cytopenias, bone marrow dysplasia and increased risk of transformation to acute myelogenous leukemia (AML). Cytogenetic abnormalities occur in more than 50% of patients (pts) and have an impact on survival and risk of transformation to AML. CE, or acquisition of additional clonal chromosomal abnormalities, has been reported to occur in 30 to 50% of primary MDS pts. Their impact on prognosis and transformation into AML among pts with low and intermediate risk MDS is not known. In this study, we analyzed the impact of CE on prognosis in lower risk MDS. Methods: we reviewed 722 pts clinic records of low and intermediate risk MDS pts at MD Anderson Cancer Center (MDACC) from 2000–2010 and conducted a retrospective analysis of all MDS pts with at least two consecutive cytogenetic analysis (365 patients, 50.6%) and compared the cytogenetic evolution group (CE group) with the group without cytogenetic changes (no CE group). Cytogenetic analysis was performed in the Cytogenetics Laboratory at MDACC. Results: CE was detected in 200 pts (55%). Characteristics of patients with CE are: median age 65 years (23-91), IPSS int-1 79%, diploid CG 42%, excess blasts 25%. Pts with CE were more frequently female (p=0.005), and had more frequently abnormalities of chromosome 5 and 7 (p<0.001) at baseline. There were no statistically significant difference between these two groups (p>0.05) regarding age, WBC, platelet, hgb, ANC, BM blasts percent, diagnosis (RA or RAEB), and IPSS score. There were more chr.-5/-7, insufficient metaphases, and other abnormalities, but less diploid cases in CE group compared with no CE group (p<0.001). History of malignancy (p=0.001) and prior chemotherapy exposure were also associated with CE (p=0.001), but this was not as strong for radiation exposure (p=0.066). Also, more CE patients required therapy for MDS compared to no CE patients (p=0.039). Progression free survival was significantly extended in no CE patients (p=0.02). Overall survival was a longer in no CE (34.1months), compared with CE group (26.2 months), although this was not statistically significant. Conclusion: CE is more commonly observed among pts with high-risk features, and is usually associated with disease progression and resistance. Also, prior malignancy and chemotherapy exposure were associated with CE in this study. This data indicates that genomic instability has a role in disease progression in MDS. Further analysis of CE in MDS is needed. Disclosures: No relevant conflicts of interest to declare.

Low Counts of Plasmacytoid Dendritic Cells After Engraftment Are Associated with Higher Early Transplantation-Related Mortality in Patients Receiving Unrelated HSCT

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4541-4541
Author(s):  
Matheus Vescovi GonÇalves ◽  
Mihoko Yamamoto ◽  
Vergílio Antônio Rensi Colturato ◽  
Mair Pedro de Souza ◽  
Marcos Mauad ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Stem Cell ◽  
Nk Cells ◽  
Hematopoietic Stem Cell ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Innate Defense ◽  
Common Diagnosis ◽  
The Impact

Abstract Abstract 4541 Background: The heterogeneous status of host immune defenses may influence the risk of infection and graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). In such defense, dendritic cells (DC) which act as specialized antigen-presenting cells that bridge the innate and adaptive immune systems, and NK-cells, responsible for the innate defense against infections and residual tumor cells, are essential cell components. Objectives: To monitor the recovery of different subsets of DC and NK cells after unrelated umbilical cord blood (UCB), bone marrow (BM), and peripheral blood (PBSC) HSCT and to evaluate the impact of the distribution of these cell subsets on the outcome of the transplant. Methods: Overall, 34 patients (median age 13y; range 1–63y) receiving a UCB (n=15), BM (n=14) or PBSC (n=5) unrelated HSCT were studied. The most common diagnosis was acute leukemia (ALL, 12 cases; AML, 10; CML, 5; aplastic anemia, 4; MDS, 2; Hodgkin lymphoma, 1; SCID, 1), a majority of patients were males (56%), and received myeloablative conditioning (MAC) regimens (73%). Antithymocyte globulin (ATG) was used in 38% and total body irraditation (TBI) in 41% of cases. Median time to neutrophil engraftment was 18 days (range: 12–45). T-cell (CD4+, CD8+, CD4−8−, CD4+8+), DC [CD123+ plasmacytoid(p)DC, CD11c+ myeloid(m)DC, and CD16+ monocytoid(mo)DC] and NK cell subsets (CD3−/CD19− 56++16− and 56+16++) were quantified by multiparametric flow cytometry at 7 sequential time points (pre-transplant, at engraftment, and at days 3, 7, 14, 21 and 60 after engraftment). Results: As compared to BM/PBSC, UCB was associated with a delayed neutrophil recovery (28 days vs. 17 days; p=0.01), and a trend to lower counts of all T-, NK- and pDC subsets, particularly for the CD4+ and CD4−/CD8− T-cells during the first 3 weeks after recovery. Conversely, no significant differences were observed between both groups as regards the distribution of mDC and moDC. The use of TBI, MAC or ATG were not associated with the reconstitution of the studied cell subsets. In contrast, patients who died from transplantation-related causes (TRM) had significantly lower counts of pDC and mDC during the first 3 weeks after HSCT. At day 21 after engraftment, the median number of pDC and mDC was 0.9 and 2.0/uL among patients who died from TRM vs. 7.1 (p=.006) and 8.4/uL (p=.01) in the remainder, respectively). Patients presenting grade II-IV acute GVHD also had significantly lower pDC counts at days 14 and 21. There was no significant association of both the hematopoietic stem cell source and the conditioning regimen on the risk of TRM or acute GVHD. Conclusion: Low pDC counts in the first weeks after unrelated HSCT are associated with an increased incidence of GVHD and mortality. The precise mechanisms that might explain the role of pDC on immunity early after HSCT deserve further investigations. Disclosures: No relevant conflicts of interest to declare.

Correlation Between Severity of cGvHD and Transplant Outcome: A Retrospective Monocenter Study Based on NIH Classification,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4088-4088
Author(s):  
Colombe Saillard ◽  
Roberto Crocchiolo ◽  
Sabine Furst ◽  
Jean El-Cheikh ◽  
Luca Castagna ◽  
...  
Keyword(s):  
Stem Cells ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Immunosuppressive Treatment ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Extensive Form ◽  
Hematopoietic Stem ◽  
Transplant Outcome ◽  
Significant Difference

Abstract Abstract 4088 Background: Chronic graft-versus-host disease (cGvHD) after allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies is associated with lower relapse rate, due to graft-versus-tumor effect. We know that the extensive form is associated with higher transplant-related mortality after myeloablative conditioning regimen, mainly due to infectious complications as a consequence of immunosuppressive treatment. Beside the “classical” Seattle classification (limited or extensive form), a recent classification (from National Institute of Health, NIH) distinguishes three levels of severity: limited, moderate and severe. We compare here both classifications for patients receiving reduced-intensity conditioning (RIC) transplant and looked for any association of cGvHD severity with transplant outcome. Patients and Methods: We evaluated data on all adult patients with hematological lymphoid or myeloid malignancies who received HSCT from related or unrelated donor, using peripheral blood stem cells, after RIC regimens (with fludarabine-busulfan-ATG) between 1998 and 2010 at the Institut Paoli-Calmettes (Marseille, France). Data on main pre- and post-transplant variables were collected; cGvHD was classified according to its presentation and severity (with both Seattle and NIH classifications) and was correlated with overall survival (OS), non relapse mortality (NRM), and relapse. cGvHD was considered as time-dependent variable, and was included in uni- and multivariate models, after adjusting for age, disease risk, HLA compatibility, graft source and comorbidity score. Relapse or death before cGvHD was considered as a competing event. Results: 283 patients were evaluated, 121 have developed cGvHD (27 limited forms and 94 extensive forms), 162 have not, for an incidence rate of 10% and 33% of limited and extensive forms respectively. Median follow up was 607 days, patients had a median age of 50 years, transplanted for acute leukemia (55), lymphoma (78), multiple myeloma (49), myelodysplastic syndrome (24), CLL (12), CML (16) or others malignancies (19). Peripheral stem cells were mostly used (294 versus 20 bone marrow graft). We had 241 related donors and 77 unrelated donors. The median day of cGvHD occurrence was 132, we found 52 de novo forms, 40 quiescent and 26 progressive forms. After reclassification with NIH criteria, we obtained 28 mild, 52 moderate and 41 severe forms. 22 of 27 limited forms were classified as mild, the extensive forms were divided into 49 moderate and 39 severe forms. In multivariate analysis, mild and moderate forms were associated with better OS compared with other groups. Severe cGvHD was associated with significant increase in NRM. Among the other variables, only age was statistically significative in OS and NRM models. Although the incidence of relapse was lower in patients with cGvHD compared with those without, no significant difference was seen between the 3 groups of patients presenting it. Conclusion: Following a fludarabine-busulfan-ATG RIC, it seems that mild to moderate cGVHD forms are associated with better OS than patients without or with severe cGVHD. This is related to lower NRM than patients with severe cGVHD and at least a comparable antitumoral effect with respect to patients without cGVHD. This invites developing strategies limiting severity but not abrogating the effect of cGVHD. Disclosures: No relevant conflicts of interest to declare.

Femoral Head Necrosis In Three Patients After Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5489-5489
Author(s):  
Gang Zhao ◽  
Zhi Li ◽  
Jiahua Ding ◽  
Jun Wang ◽  
Zhengping Yu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Femoral Head ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Femoral Head Necrosis ◽  
Hematopoietic Stem

Abstract Femoral head necrosis (FHN) is one of common complications after hematopoietic stem cell transplantation (HSCT). It impacts on patients' normal life with severe pain. To investigate FHN after allogeneic HSCT, We performed retrospective analyses. Since 2003, our department has conducted 98 cases of allogeneic hematopoietic stem cell transplantation for patients with hematologic diseases. Chemotherapy regimens and transplant conditioning regimen before transplantation were steroid-free. FHN occurred in 3 out of 98 cases. The 3 patients were treated with steroid for preventing graft versus host disease (GVHD) after transplantation. However, all the three patients suffered from GVHD, which was cured with steroidal medication subsequently. Then, symptoms of FHN come out and were significantly improved after conservative treatment in all the three patients. The occurrence of FHN might be associated with GVHD and corticosteroids prescription. Early prevention might be helpful in reducing the incidence and improving outcomes. Disclosures: No relevant conflicts of interest to declare.

CTLA-4 Polymorphisms and Haplotype Correlate with Survival and aGVHD after Allogeneic Stem Cell Transplantation from Related HLA-Haplotype-Mismatched Donor

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2006-2006
Author(s):  
Xiao-Ying Qin ◽  
Yu Wang ◽  
Guo-Xuan Li ◽  
Yazhen Qin ◽  
Lan-Ping Xu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflict Of Interest ◽  
Conflicts Of Interest ◽  
Immunosuppressive Agents ◽  
Negative Regulator ◽  
Hematopoietic Stem ◽  
The Impact ◽  
Mismatched Donor

Abstract Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been established as an effective treatment for patients with hematological malignancies. Disease relapse remains a major cause of transplant failure.T cell homeostasis is critical to determine the potency of the GVT effect. Cytotoxic T lymphocyte antigen-4 (CTLA-4 or CD152) is a T cell activation negative regulator. Recent studies have shown the association of the CTLA-4 polymorphisms with the outcome after HLA-identical sibling allogeneic HSCT. Patients and Methods: In this study, we focused on four CTLA-4 polymorphisms, and analyzed the impact of donor genotypes and haplotypes on the conditions of 154 acute leukemia patients after related HLA-haplotype-mismatched transplantation. The four SNP genotypes (-1661, -318, CT60 and +49) were determined by TaqMan SNP genotyping assays. Results: Recipients of donors with +49 GG showed significantly lower OS (69.1% vs. 85.6%, P=0.024) and higher incidence of III-IV aGVHD (10.0% vs. 2.1%, P=0.032) than those with GA + AA(Fig.1,Fig.2). Multivariate analyses showed that +49GG was an independent risk factor for OS (HR:0.457,95%CI=0.227-0.920,P=0.028). Patients receiving mDLI showed significantly lower OS with +49 GG donor than those with AG+AA (P=0.011).The haplotype analysis revealed only three haplotypes in the donor population -1661/-318/CT60/+49 i.e.,ACGG,ACAA and GTGA,the frequencies were 64.3%, 19.5%, and 16.2%, respectively.Donors with and without the ACGG/ACGG haplotype had the same effect on transplant outcome as those with +49 GG and +49 AG+AA. Conclusion: The CTLA-4 +49 GG and the haplotype ACGG/ACGG reduced the overall survival and increased the aGVHD after allo-HSCT from the related HLA-haplotype-mismatched donor,knowledge of the CTLA-4 polymorphism and haplotype may provide useful information for donor selection and individual application of immunosuppressive agents and immunotherapy. CONFLICT OF INTEREST The authors declare no conflict of interest. Disclosures No relevant conflicts of interest to declare.

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