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.

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.

Cytomegalovirus and Effect on Early Chimerism in Patients with Myeloid Disorders Undergoing Stem Cell Transplantation Using Reduced Toxicity Ablative Conditioning Regimen

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5446-5446
Author(s):  
Shatha Y. Farhan ◽  
George Divine ◽  
Klodiana Neme ◽  
Danielle Pelland ◽  
Susan Wautelet ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Disease Risk ◽  
Conditioning Regimen ◽  
High Risk Patient ◽  
Hematopoietic Stem ◽  
The Mean ◽  
Reduced Toxicity ◽  
The Impact

Abstract Cytomegalovirus (CMV) remains a significant cause of morbidity after allogeneic hematopoietic stem cell transplantation (SCT). The influence of CMV on the chimerism in reduced toxicity ablative conditioning SCT in myeloid disorders is ill defined. A recent report published in Blood by Sellar et al showed that in patients who received alemtuzumab-based regimen, the group of patients who were recipient positive (R+)/ Donor negative (D-) had CMV-specific T cells that are exclusively of recipient origin and significantly influenced the chimerism status toward recipients. To explore the impact of seropositivity and seronegativity of CMV in recipients and donors on early chimerism, we undertook a retrospective analysis of patients with myeloid disorders who received four days of fludarabine and busulfan with or without anti-thymocyte globulin (ATG) at our center in the last 10 years. Methods: Chimerism assay was performed using a quantitative fluorescence-based short tandem repeat-polymerase chain reaction (STR-PCR) with capillary electrophoresis for PCR product resolution. Results: 42 patients were identified and included in the study. All patients received fludarabine (40 mg/m2/day x 4 doses), busulfan (3.2mg/kg/dose IV x 4 doses). Of these 42 patients, 25 had anti-thymocyte globulin. There were 28 male and 14 female patients with a median age of 62 years (range 48-74yrs). Median time to follow up was 8 months (0.8-54 months). Disease risk was considered advanced in 21 patients, intermediate in 4 and early in 17. Median blast number at time of SCT was 5%. Stem cell source included peripheral blood in all patients. There were no primary graft failures. Total recipient cell chimerism showed increase or persistence of recipient chimerism in 5/11 (45%) of R+D- vs 2/6 (33.3%) of R-D- in the group of patients who received ATG, p=1.0, with a mean of recipient chimerism at day 100 of 20.4% in the R+D- group compared to a mean of 17% in the R-D- group. In the group who did not get ATG, recipient chimerism persistence or increase was not that different between the R+D- patients 3/4 (75%) compared to 4/4 (100%) in patients who were seronegative for CMV (R-), p=1.0. The mean of recipient chimerism at day 100 in the R+D- no ATG group was 23.25% with a median of 12% while the mean and median at day 100 in the R- no ATG group were 35.25% and 19.5% respectively (p=0.573).When looking at the persistence or increase in recipient chimerism in the group of patients who were R+D-, in those who got ATG it was 45% increase vs 75% increase in those who did not get ATG (p=0.569) with a median of 12% vs 0% respectively (p=0.49). Also increase or persistence of recipient chimerism was 33.3 % in patients who were R- and got ATG vs 100% in R- no ATG patients (p=0.076)with median at day 100 of 0 vs 19.5% (p=0.098). Conclusion: In this small cohort from a single center, we found that in patients with myeloid disorders who received reduced toxicity ablative conditioning regimen, the group of patients who received ATG, there was no statistically significant increase in recipient chimersim in the R+D- group compared to R-D- group. This is different from what Sellar et al found in a small group of patients who received alemtuzumab. These results may indicate a difference between ATG and alemtuzumab in the effect of CMV seropositivity and negativity on the recipient chimerism, which need to be studied further in a larger retrospective or prospective study. This is especially important in myeloid disorders since persistent or increase in recipient chimerism may identify high-risk patient cohorts who may benefit from additional therapeutic interventions. Disclosures No relevant conflicts of interest to declare.

scholarly journals Impact of chronic khat (Catha edulis Forsk) chewing on pulmonary function test and oxygen saturation in humans: A comparative study

2019 ◽  
Vol 7 ◽  
pp. 205031211882461 ◽  
Author(s):  
Gashaw Garedew Woldeamanuel ◽  
Teshome Gensa Geta
Keyword(s):  
Lung Function ◽  
Pulmonary Function ◽  
Oxygen Saturation ◽  
Vital Capacity ◽  
Forced Expiratory Volume ◽  
Mean Values ◽  
Khat Chewing ◽  
Significant Difference ◽  
The Mean

Background: Chronic consumption of khat affects many organ systems and leads to various health disturbances in the chewers. Few studies examined the acute effects of khat ingestion on lung function parameters. However, studies which assessed the long-term effects of khat chewing on pulmonary function parameters and oxygen saturation are lacking. Objective: The aim of this study was to assess the impact of chronic Khat chewing on pulmonary function parameters and oxygen saturation among chronic Khat chewers in Wolkite, Ethiopia. Methods: A community-based comparative cross-sectional study was conducted in Wolkite, Ethiopia from 1 June 2018 to 15 August 2018. A total of 324 participants, 162 khat chewers and 162 non-chewers were included in the study. The data were collected through face-to-face interview by trained data collectors. British Medical Research Council respiratory questionnaire was used to assess respiratory symptoms. A spirometer was used to assess various lung function parameters. Moreover, oxygen saturation of hemoglobin was measured using pulse oximeter. Data were entered into CSPro version 6.2 and analyzed using SPSS version 23. Results: This study showed statistically significant (p < 0.05) reduction in the mean values of forced vital capacity, forced expiratory volume in first second and maximum ventilation volume among khat chewers as compared to non-chewers. There was no significant difference in the mean values of other lung function parameters between the two groups. Similarly, there was no significant difference (p = 0.642) in mean oxygen saturation of hemoglobin (SaO2) across the two groups. Conclusion: It is evident from this study that long-term khat consumption is associated with decreased mean forced vital capacity, forced expiratory volume in first second and maximum ventilation volume. Hence, there is a need for further study to strengthen the current findings and to explore the mechanisms of khat chewing effect on lung function parameters.

Intravenous Busulfan: Pharmacokinetic Disposition and Clinical Outcomes in Children Undergoing Hematopoietic Stem Cell Transplant.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1760-1760
Author(s):  
Tal Schechter ◽  
Yaron Finkelstein ◽  
John Doyle ◽  
Zulfikaral Verjee ◽  
Gideon Koren ◽  
...  
Keyword(s):  
Stem Cell ◽  
Oral Administration ◽  
Hematopoietic Stem Cell ◽  
Conditioning Regimen ◽  
Significant Proportion ◽  
Pharmacokinetic Parameters ◽  
Cell Transplant ◽  
Older Children ◽  
Hematopoietic Stem ◽  
The Mean

Abstract Background: Conditioning regimens preceding hematopoietic stem cell transplantation (HSCT) for various malignant and non-malignant diseases in children often include busulfan. Busulfan administration may be complicated by hepatic veno-occlusive disease (HVOD). A relationship has been described between high systemic exposure to busulfan after oral administration, as measured by area under the curve (Bu-AUC) and HVOD. Recently, IV busulfan (IV Bu) administration has been reported to be associated with a much lower incidence of HVOD than oral administration in adults. Objectives: To describe the pharmacokinetics of IVBu in infants (&lt;1 year of age) and children. To determine the incidence of HVOD in children undergoing conditioning with IV Bu, and to correlate IV Bu AUC with the development of HVOD and neutrophil engraftment. Methods: Twenty-four children who underwent HSCT at The Hospital for Sick Children between April 2003 and September 2004 and received IV Bu as part of their conditioning regimen were included in this retrospective study. Diagnoses included: AML (6), metabolic storage disease (6), immune deficiency syndromes (4), histiocytosis (2), beta-thalassemia (2), WAS (1), MDS (1), CML (1), relapsed meduloblastoma (1). Initial IV Bu doses were based on actual patient weight: &lt;9kg =0.95mg/kg/dose; 9–16kg =1.2mg/kg/dose; 16–23kg =1.1mg/kg/dose; 24–34kg =0.95mg/kg/dose; &gt;34kg =0.8mg/kg/dose. Seven blood samples were drawn after the first IV Bu dose for determination of plasma busulfan concentrations. Pharmacokinetic parameters were calculated using 1-compartment analysis (WinNonLin 4.1). The third and subsequent IV Bu doses were adjusted to achieve an AUC of 900–1500μMol•min. HVOD (modified Baltimore criteria) and engraftment (ANC &gt; 0.5 x 109/L) were evaluated. Results: The median patient age was 3.5 years (range 3mo–16.9yrs), including 9 infants. Mean IV Bu pharmacokinetic parameters were: Cmax=4.7±0.9μMol; Vss=0.70±0.22L/kg; ke=0.005±0.001min−1; AUC=1256±320μMol•min. The mean IV Bu AUC of infants was not different from older children (1164μ±331Mol•min vs. 1311±311μMol•min; p=0.35). The mean Vss was higher in infants than older children (0.84±0.29L/kg vs. 0.62±0.10L/kg; p=0.025), but the mean clearance was not different when corrected for body weight. Twenty-three patients (95.8%) engrafted between day +10 to +27. HVOD was diagnosed in 6 patients (25%), including 3 infants. Five patients had moderate HVOD and one had fatal HVOD. Mean IV Bu AUC was 1317±310μMol•min and 1074±299μMol•min in the non- HVOD vs. the HVOD group, respectively (p=0.10). The number of children who did not engraft precluded assessment of the relationship between IV Bu AUC and engraftment. Conclusions: Busulfan Vss differs significantly between infants and older children. A significant proportion of patients developed HVOD. No association was observed between IV Bu AUC and the development of HVOD in children where busulfan doses are adjusted to achieve a target IV Bu AUC.

Pre-Transplant Test Dose vs. PK Studies during Conditioning Regimen To Target iv Busulfan in Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3006-3006
Author(s):  
Sandeep Chunduri ◽  
Rakesh Beri ◽  
Lisa C. Dobogai ◽  
Elizabeth Hurter ◽  
Christina Mactal-Haaf ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Conditioning Regimen ◽  
Test Dose ◽  
Hematopoietic Stem ◽  
Blood Samples ◽  
The Mean

Abstract In this study we tested the efficacy of a test dose of iv busulfan in targeting blood levels of this drug during the conditioning regimen prior to an allogeneic hematopoietic stem cell transplant. We analyzed blood samples of 22 patients undergoing allogeneic hematopoietic stem cell transplantation with a busulfan-based conditioning regimen. Patients received a test dose of busulfan at 0.8 mg/kg as a 60 minute intravenous infusion. Serial blood samples were drawn at eight time points: 15 minutes before dose, at end of infusion, 15 minutes after completion, 30 minutes after completion, 60 minutes after completion, 2 hours after completion, 4 hours after completion, and 6 hours after completion. Pharmacokinetics (PK) studies were then performed at the Seattle Cancer Care pharmacokinetics laboratory. The AUC was determined using WinNonlin Professional software. The conditioning dose of busulfan was calculated by multiplying the test dose in mg/AUC × 4800. After the first dose of busulfan was administered, the same protocol was used to test busulfan PK. If the Busulfan AUC was therapeutic (between 4800 μM*min and 5200 μM*min) then the same dose was continued. If the Busulfan AUC was low or high then the third and fourth doses of busulfan were adjusted. The test dose of 0.8 mg/kg intravenous did not have any hematological side effects. The mean historic dose (solely based on weight) was 3.2 ± 0.1 mg/kg and the mean dose based on the test dose was 3.5 ± 0.5 mg/kg (p=0.02). In 12 patients where we also analyzed PK after the first day of conditioning regimen, AUC values of busulfan obtained during test dose and after day 1 dose were not different (p=0.7). The mean dose of busulfan based on test dose was 3.5 ± 0.6 mg/kg while the final dose based on day 1 busulfan PK was 3.6 ± 0.7 mg/kg (p=0.9). Nevertheless, in 2 CML patients who were on treatment with dasatinib or nilotinib at the time of the test dose, a higher AUC was observed (AUC 6065 and 6200, respectively). A pre-transplant busulfan test dose can be safely performed anytime prior to transplant and allows targeting the dose of busulfan efficiently, thus avoiding the requirement of PK studies during the conditioning regimen.

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.

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.

scholarly journals The Impact of Age in Allogeneic Stem Cell Transplantation with Thiotepa Busulfan and Fludarabine (TBF) for Myelofibrosis : A Retrospective Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4858-4858
Author(s):  
Federica SORA ◽  
Patrizia Chiusolo ◽  
Sabrina Giammarco ◽  
Idanna Innocenti ◽  
Francesco Autore ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Total Dose ◽  
Cell Transplantation ◽  
Older Patients ◽  
Research Funding ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Allogeneic hematopoietic stem-cell transplantation (HSCT) currently remains the only curative therapy for intermediate or high risk disease.myelofibrosis (MF). We are reporting 56 patients (pts) who underwent an allogeneic HSCT in our Centre between 2016 and 2020, and assessed factors predictive of outcome. The median age was 59 years (36-72). Most patients (72%) were JAK2+ and had int2-high DIPSS (92%). The conditioning regimen consisted of thiotepa, busulfan , fludarabine (TBF). All pts received thiotepa 10 mg/kg and fludarabine 150 mg/m^2. The dose of busulfan was adjusted considering the age and the comorbidity score. One pt received 3 days of busulfan (total dose 9.6 mg/kg); 47 received 2 days (total dose 6.4 mg/kg) and 8 received one day of busulfan iv (3.2 mg/kg). Donor was an identical sibling in 13 pt, haploidentical in 18, matched unrelated donor (UD) in 18 and a mismatchedUD in 7. Thus we had 31 HLA matched and 25 HLA mismatched grafts. Fortytwo patients received post-transplant cyclophosphamide (PTCy)-based GVHD (Graft versus host disease ) prophylaxis with cyclosporine and mycophenolate mofetil , and 14 patients received a standard GvHD prophylaxis (CSA+MTX+ATG). The 2 year survival (OS) was 73 % and disease free survival (DFS) was 66 % and the cumulative incidence (CI) of TRM was 23% and of relapse 11%. The incidence of acute GvHD grade II-IV was 22% in HLA matched and 50% in HLA mismatched pts (p=0.022), grade III-IV was 6% and 25% respectively (p=0.042) . The incidence of moderate-severe chronic GvHD was 25% in HLA matched and 36% in HLA mismatched grafts (p=0.36). HLA had a major impact on survival : 85% vs 49% survival for matched vs mismatched patients (p=0.01). Patients age &gt;60 years had a major impact on outcome, with a 2 year survival of 51% vs 88% in patients over (n=24) or under 60 years of age (n=32) (p=0.007; the DFS was 46 % and 80% respectively and the CI of TRM was 42% vs 9% (p=0.003). As to the total dose of busulfan, we found 26% TRM in patients receiving busulfan for 2 days (total doe 6.4 mg/kg) (n=47) and 0% in older patients receiving 1 day only (total dose 3.2 mg/kg) (n=8) ; relapse rate was 10% and 20% respectively. In multivariate cox analysis including age, spleen size ,DIPSS score, number of transfusion received and donor type, only HLA matching influenced the incidence of acute GvHD; transfusion burden and age plays a role in NRM and OS; DIPSS predicts relapse . In conclusion: older patients with MF have a high NRM and need to be prepared with a milder conditioning regimen. Disclosures Laurenti: Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Honoraria; BeiGene: Honoraria. Sica: Pfizer: Honoraria.

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.

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