Umbilical Cord Blood Transplant after Reduced Intensity Conditioning Provides Outcomes Comparable HLA-Matched Siblings for Patients with High Risk and Advanced Acute Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 606-606 ◽  
Author(s):  
Claudio G. Brunstein ◽  
Daniela Setubal ◽  
Marcie Tomblyn ◽  
Todd DeFor ◽  
Mukta Arora ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Risk ◽  
Conditioning Regimen ◽  
Disease Status ◽  
P Value ◽  
Limiting Factor ◽  
Hematopoietic Stem ◽  
Cell Dose ◽  
Matched Sibling ◽  
Total Body

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is a standard treatment for patients with high risk or advanced AML. However, older age and of co-morbidities frequently limit its use due to high risk of regimen related toxicities (RRT) after a myeloablative regimen. While the inception of RIC regimens has been very successful at reducing RRT, lack of available HLA matched sibling or unrelated donors has become the principal limiting factor. We hypothesized that UCB would increase the utilization of HSCT in patients with AML who lacked a HLA-matched, medically suitable sibling donor. Therefore, we evaluated the various transplant outcomes in 64 AML patients treated with RIC followed by transplantation with HLA-matched sibling PBSC (n=21) and 4–6/6 HLA matched UCB (n=43). All pts received Fludarabine (Flu, 200 mg/kg) and total body irradiation (TBI 200 cGy) with either cyclophosphamide (Cy 50 mg/kg, n=49) or Busulfan (Bu 8 mg/kg, n=15). All pts received cyclosporine A and mycophenolate mofetil GVHD prophylaxis. UCB grafts were composed of 1 (n=15) or 2 (n=28) units to achieve the minimum cell dose. Patients with good and intermediate risk cytogenetics in first complete remission (CR1) were classified as standard risk; others were classified as high risk. Multivariate models considered: donor type, age, disease status, weight, CMV serostatus, cytogenetic risk, disease risk, acute GVHD, conditioning regimen, and time from diagnosis to HSCT. The proportion of engraftment (88% vs. 100%, p=0.10), the incidence of grade II–IV GVHD at day 100 (51% vs. 62%, p=0.85) and TRM at 1 year (28% vs 38%, p=0.43) did not differ between UCB and PBSC recipients. Similarly, relapse at 2 years (UCB 35% vs SIB 35%, p=0.72) and 2 year survival (UCB 31% vs SIB 32%, p=0.62) were comparable. In multivariate analysis, only disease risk group was associated with increased relative risk (RR) of relapse (RR 2.9, 95%CI, 1.3–6.2, p<0.01) and death (RR 2.6, 95%CI, 1.1–5.5, p=0.02). These results demonstrate that partially HLA matched UCB after RIC markedly extends the availability of HSCT with results comparable to those observed with PBSC from HLA matched sibling donors. Variable UCB (n=43) SIB PBSC (n=21) p value * Cell doses of double UCB grafts=combined cell dose. Age in years - median (range) 53 (22–68) 54 (19–69) 0.77 Weight in kg - median (range) 75 (53–120) 72 (51–112) 0.24 Recipient/Donor CMV + 20 (47%)/− 13 (62%)/8 (38%) <0.01 HLA-match 6/6* 5 (7%) 21 (100%) HLA-match 4–5/6* 66 (93%) Zero Disease status CR1 18 (43%) 14 (67%) Cytogenetics good/intermediate 32 (84%) 10 (48%) 0.31 Cytogenetics poor risk 7 (16%) 10 (48%) TNC X10 7/kg median (range)* 3.6 (1.6–5.9) 93.4 (64.8–212.3) CD34 X105/kg median (range)* 4.9 (1.1–18.8) 52.2 (14.1–153.7) Median follow-up in years 2.7 (0.7–5.5) 1.3 (0.7–6.1)

Late Pulmonary Dysfunction in Long-Term Survivors after allogeneic Hematopoietic Stem Cell Transplantation with Intensified Conditioning Regimen Including Thiotepa, Cyclophosphamide, and Total Body Irradiation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2137-2137
Author(s):  
Satomi Ito ◽  
Maki Hagihara ◽  
Kenji Motohashi ◽  
Atsuo Maruta ◽  
Yoshiaki Ishigatsubo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Pulmonary Dysfunction ◽  
Hematopoietic Stem ◽  
Related Donor ◽  
Total Body ◽  
Long Term Survivors

Abstract Background: Late pulmonary dysfunction is a clinical problem influencing on quality-of-life (QOL) in long-term survivors after allogeneic hematopoietic stem cell transplantation (HSCT). In this study we retrospectively assessed pulmonary function test (PFT) in patients surviving 5 years or more after HSCT with intensified conditioning regimen and identified pre-and post-transplant risk factors. Methods: Sixty-five long-term survivors transplanted between May 1994 and March 2003 (minimum 5 years follow-up after HSCT) were included in this analysis. There were 36 males and 29 females. Median age was 39 years, with a range of 16 to 53 years. All patients were transplanted because of hematologic malignancies (20 patients with AML, 16 with ALL, 9 with MDS, and 20 with CML). The pre-transplant conditioning regimen consisted of thiotepa (200 mg/m2 for 2 days), cyclophosphamide (2,000–2,250 mg/m2 for 2 days), and total body irradiation (12.5 Gy in five fractions). The prophylaxis of graft-versus-host disease (GVHD) consisted of short-term methotrexate and cyclosporine or tacrolimus. Bone marrow (BM) from related donor or unrelated donor, and peripheral blood stem cell (PBSC) from related donor were transplanted in 33 patients, 22, and 10, respectively. PFT was performed pre-conditioning and then post-transplant at 3 months, 1 year, and thereafter annually. Forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and FEV1/FVC ratio were used to measure ventilatory capacity. Vital capacity (VC) and total lung capacity (TLC) were used to measure lung volumes. Diffusion capacity for carbon monoxide (DLCO) was determined by using a carbon monoxide single-breath technique with correction for hemoglobin concentration. Results: Seven (11%) patients showed abnormalities in PFT after HSCT. Temporary abnormality (restrictive pattern) within 1 year was detected in 2 patients. Five patients developed late-onset and continuous abnormality (restrictive pattern in 2 patients, obstructive in 2, and mixed in 2) with a cumulative incidence of 8%. These were clinically diagnosed as having bronchiolitis obliterans in 3 patient and interstitial pneumonia in 1. DLCO was significantly lower after transplantation of PBSC than after BM (P=0.02 at 3 year and P=0.00 3 at 5 year). More than 40 years old, female, high risk of disease status, and abnormal PFT pre-transplant were related with a decline of PFT within 1 year after HSCT, but there were no association with PFT abnormality at 3 or 5 years. The cumulative incidence of late PFT abnormality in patients with CML was significantly higher than that in those with other than CML (P=0.01).Other factors including age, sex, smoking, disease status, and donor sources were not significant for developing late pulmonary dysfunction. Extensive chronic GVHD was associated with late PFT abnormality with statistical significance (P=0.002 for VC and P=0.01 for FEV1). Three of 7 patients receiving immunosuppressant at 5 years after HSCT had pulmonary complication. Conclusions: The results showed relatively a low incidence of PFT abnormality in long-term survivors who received HSCT with intensified conditioning regimen. However, late pulmonary dysfunction lowers QOL in survivors despite long-term remission of leukemia Longer follow-up should be needed to determine whether more patients with chronic GVHD will develop PFT abnormality.

Impact of Cytopenia Following Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation Using Post-Transplant Cyclophoshamide

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2281-2281
Author(s):  
Villetard Ferdinand ◽  
Stefania Bramanti ◽  
Samia Harbi ◽  
Sabine Fürst ◽  
Catherine Faucher ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Transplantation ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Risk Index ◽  
Conditioning Regimen ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Cell Dose ◽  
The Impact

Abstract Introduction Allogeneic transplantation from a haploidentical donor (HaploSCT) is an alternative strategy in the treatment of hematologic malignancies in absence of HLA-identical donor. Recent studies reported similar outcome after HaploSCT compared to HLA-identical transplantation in different settings (Bashey, JCO 2013; Wang, Blood 2015; Gosh, JCO 2016). Although survivals seemed promising after HaploSCT, hematopoietic recovery following such a mismatched transplantation could represent a limitation. Thus, our series aims to evaluate hematological recovery after HaploSCT using a post transplantation cyclophosphamide (PT-Cy) platform. Methods This retrospective monocentric study included consecutive patients with following criteria: adults with hematological malignancies; bone marrow or peripheral blood T-replete HaploSCT from 2011 to 2015; non-myeloablative (Baltimore approach) or reduced intensity conditioning (busulfan-based) regimen; PT-Cy as part of GVHD prophylaxis. Patients with primary graft failure were excluded. Absolute neutrophil count (ANC), red cells (RCT) or platelet transfusion (PT) requirements on day 30 (D30) and day 100 (D100) were analyzed among disease-free patients. We first separately evaluated the rate of patients with significant cytopenia in each lineage (defined by ANC < 1 G/L, RCT need, PT need) and searched for impact of pre-transplantation factors on cytopenia (multivariate analyses by binary logistic regression). Then, we evaluated outcome by D30- and D100-landmark analyses according to cytopenia. Results One hundred and forty six patients with a median age of 56 years (range: 19-73) were analyzed: 142 and 117 were evaluable at D30 (4 early deaths) and D100 (17 deaths, 11 relapses), respectively. At D30, 20% of patients had ANC<1G/L, 67% needed RCT and 63% needed PT. Corresponding values at D100 were 20%, 42% and 28%, respectively (Figure 1). At D30: the use of PBSC (HR 9.5, p=0.002) was significantly associated with ANC>1G/L at D30; the use of NMAC Baltimore schema (HR 0.3, p=0.012) and CD34+ cell dose > median (HR 0.4, p=0.041) decreased PT needs while hematopoietic cell transplantation comorbidity index (HCT-CI)≥3 (HR 3.3, p=0.004) was associated with PT needs; no factor was found to significantly influence RCT. At D100: Age>60 years (HR 2.4, p=0.045), female to male HaploSCT (HR 3.3, p=0.020) and HCT-CI≥3 (HR 3.7, p=0.006) were significantly associated with higher risk of RCT need; female to male HaploSCT (HR 3.6, p=0.015) and HCT-CI≥3 (HR 6.9, p=0.001) were associated with PT needs; no factor was found to significantly influence ANC. With a median follow up of 25 months (range: 5-55), cox multivariate model with adjustment by age (continuous), disease risk index (low/intermediate vs high/very high), HCT-CI (0-2 vs ≥3), conditioning regimen (baltimore vs. busulfan-based) and graft source (bone marrow vs PBSC) showed that ANC<1 G/L was strongly associated with higher NRM (HR 2.9, p=0.011) and shorter OS (HR 3.4, p<0.001), overcoming the impact of RCT and PT needs (Figure 2A and 2B). In contrast, D100 analysis showed that PT need was the most determinant factor of increased NRM (HR 13.7, p=0.013) and poor OS (HR 7.3, p=0.003), while both D100 ANC and RCT needs did not impact outcome (Figure 2C and 2D). Discussion We found that cytopenia remain a concern after HaploSCT, leading to increased NRM and OS. The absence of ANC>1G/L at D30 as well as the need of PT at D100 may be considered as a strong post transplantation factor predicting poor outcome. Some pre-transplantation factors of cytopenia have been identified, such as CD34+ cell dose, sex mismatch and graft source. Among them, some may help for donor selection while the optimal donor for HaploSCT is still unknown. Moreover, better neutrophil recovery at D30 is achieved with the use of PBSC. CD34+ optimal cell dose in this setting remains also to be determined. In addition, post transplantation events such GVHD and/or infections should be evaluate to explore their interactions with such cytopenia, aiming to develop early therapeutic interventions. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Optimizing the Outcomes of Allogeneic Hematopoietic Stem Cell (HSC) Transplantation for Hematological Malignancies: The Perfect Combination of Conditioning Regimen, Disease Stage and Type of HSC Donor

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4324-4324
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Hélène Labussière-wallet ◽  
Marie Balsat ◽  
Caroline Lejeune ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Hematological Malignancies ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Disease Stage ◽  
Hla Matching ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative strategy for a majority of patients with high-risk hematological malignancies. Several studies have evaluated the impact of conditioning intensity on the long-term transplantation outcomes, mainly retrospective and derived from large registries or non-randomized trials. These studies showed that more intensive conditioning (MAC) regimens are associated with a reduced risk of relapse, but do not translate into improvement of survival due to increased non-relapse mortality (NRM). Reduced intensity/Non-myeloablative conditioning (RIC/NMA) through graft-versus-leukemia effect has been associated with lower NRM, but higher relapse rates leading to similar overall survival (OS) when compared to MAC. However, in daily clinical practice, these results are difficult to follow because of the combination of important impact of disease stage, the type of HSC donor and its HLA matching with the patient. In addition, the historical nature of the previous studies may lead to the observation of different results today as the experience in drugs toxicities management has changed over time. The objective of this study is to evaluate the impact of the conditioning regimen intensity taking into account the disease stage and the type of HSC donor with its HLA matching on transplantation outcomes in a large population of patients with high-risk hematological malignancies. Material and methods A total of 542 patients who received allo-HSCT between January 2006 and December 2014 in our center were included, 321 (59%) were males, the median age at allo-HSCT was 49 years (range: 18-70). There was 256 (47%) acute leukemia (202 AML, 54 ALL), 61 (11%) MDS, 60 (11%) multiple myeloma, 46 (8%) NHL, 25 (5%) Hodgkin's disease, 23 (4%) myeloproliferative neoplasms, 21 (4%) CML, 12 (2%) CLL and the rest with other hematological diseases. All patients were classified as at high-risk according to either clinical, immunophenotypic, cytogenetic or molecular markers. Conditioning regimen was classified as recently published (Gyurkocza et al. Blood 2014), therefore 282 (52%) received MAC and 260 (48%) received RIC/NMA; at allo-HSCT 320 (59%) patients were in CR and 222 (41%) in less than CR. HSC donor was identical siblings (Sib) for 199 (37%) patients (100 BM, 99 PBSC), 10/10 HLA matched unrelated (MUD) for 159 (29%) (79 BM, 80 PBSC), 6/6 HLA matched double cord blood (CB) units for 12 (2%), 9/10 HLA mismatched unrelated (MMUD) for 114 (21%) (54 BM, 60 PBSC), and the rest of 58 (11%) were 5/6 or 4/6 MM double CB units. For sex mismatching, in 119 (22%), it was female donor to a male patient; 295 (54%) were ABO compatible, 105 (20%) had minor incompatibility and 142 (26%) major incompatibility. Results The median follow-up for surviving patients was 29 months (range: 4-96). We conducted a cox multivariate model for OS including patient age, disease status at allo-HSCT, conditioning regimen, type of donor and HLA matching, in addition to ABO and sex mismatching, with stratification on the type of disease; this model showed a significant impact of disease status in favor of CR (HR=1.5, 95%CI: 1.2-2.0, p=0.001), conditioning regimen in favor of MAC (HR=0.68, 95% CI: 0.53-0.88, p=0.003) and type of donor in favor of Sib (HR=0.68, 95%CI: 0.5-0.9, p=0.01). Interestingly, we were able to find an optimal association between these 3 factors leading to significantly better results in terms of OS and NRM independently of the disease type. When in CR, patients receiving MAC from Sib or from MUD had significant better OS and NRM compared to the rest of patients with 5-years rates of 71% vs 36% (p<0.0001) and 15% vs 37% (p=0.001) respectively. If not in CR, only patients who received HSC from Sib either after RIC or MAC showed significantly better OS and NRM compared to the rest of patients with 5-years rates of 50% vs 26% (p=0.001) and 22% vs 45% (p=0.008) respectively (see Figure). Considering only MMUD, patients receiving CB with RIC had better OS and NRM rates compared to 9/10 MMUD (RIC or MAC) and to MAC CB (p=0.07). Conclusion We provide in this large study, a practical daily clinical practice outcome preview after allo-HSCT, independently of the type of disease, for the combination of significant impacting factors namely disease status at allo-HSCT, conditioning regimen and type of HSC donor with a superiority for MAC when used in CR from Sib or MUD. Figure 1. Figure 1. Disclosures Nicolini: Ariad Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Comparison of Different TBI Based Conditioning Regimen in Pediatric Haematological Malignancies: A Retrospective Study of 702 Patients from French Registry.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 840-840
Author(s):  
C. Maurin ◽  
P. Bordigoni ◽  
G. Michel ◽  
K. Yakouben ◽  
E. Gluckman ◽  
...  
Keyword(s):  
Retrospective Study ◽  
High Risk ◽  
Hematological Malignancies ◽  
Conditioning Regimen ◽  
Chronic Phase ◽  
Low Risk ◽  
P Value ◽  
Total Body ◽  
French Registry

Abstract Rational: HSCT is widely used as treatment of poor-risk pediatric hematological malignancies from 80’s. Many different TBI or busulfan based conditioning regimen have been developed. Although many studies have compared TBI vs busulfan, few studies were available for evaluating different TBI based regimen. Methods: In order to compare efficacy, safety and toxicity of these different TBI based regimen, we realized retrospective study regarding HSCT in pts under 18 years of age from French HSCT registry from 1985 to 2004. P value under 0.05 was considered as statistically significant. Results: A total of 702 pts were transplanted during this period using 26 different TBI based conditioning regimen but just 4 of them included more than 30 patients: TBI+Cyclophosphamide (R1, n=305), TBI+Cytarabine+Melphalan (R2, n=249), TBI+VP16 (R3, n=35) or TBI+Cyclophosphamide+VP16 (R4, n=30). We exposed here the results of 554 pts given either R1 or R2. Main characteristics and results are summarized in table. Engraftment rates were similar in R1 and R2. Ten years OS was significantly better for R1 vs R2 (57.8+/−4.1% vs 48.8+/−4%, P=0.0008). There were no significant differences for both conditioning regimen regarding the risk of relapse (R1: 35.8+/−3.9% vs R2: 27.6+/−3.9%), the risk of grade III and IV aGVHD (R1: 16.7+/−2.2% vs R2: 20.01+/−2.6%) and the risk of cGVHD (R1: 26.9+/−3.2% vs R2: 32.4+/−5.2%). TRM at 10 years was significantly worse for R2 vs R1 (33+/−3.3% vs 22.8+/−2.8%, P=0.004). The results obtained with TBI+VP16 were similar than those with TBI+Cy where the results from TBI+VP16+Cy were closed to those from TBI+Arac+Melphalan (data not shown). Discussion and Conclusion: Too many different TBI based conditioning regimen were used. In order to standardize procedures among transplant centers, we would like identify a gold standard. In our study, TBI + Cy appears safer than TBI+Cytarabine+Melphalan as conditioning regimen for pediatric hematological malignancies since OS and TRM were better although same relapse and GVHD rates were obtained. Main characteristics TBI + Cy (n=305) TBI+Arac+MEL (n=249) TBI: total body irradiation; Cy: cyclophosphamide; Arac: cytarabine; MEL: melphalan % of male 56 62 Median age at diagnosis (years) 11 (0–17.7) 5 (0.8–17.1) Median age at graft (years) 12.5 (0.4–18) 8.5 (1.9–17.8) Median time from diagnosis to graft (months) 8 (2–173.3) 24 (3–151) Diagnosis ALL low risk/high risk 139(46%)/17(6%) 191(77%)/30 (12%) AML low risk/high risk 46(15%)/43(14%) 3(1.2%)/7(2.8%) MDS 12 (4%) 4 (1.6%) CML chronic phase/other (%) 28(9%)/5(1.6%) 2(0.8%)/1(0.4%) Source of Stem Cells Bone marrow 222 (73%) 221 (89%) Peripheral blood 22 (7.3%) 5 (2%) Cord blood 60 (20%) 19 (7.6%) Sibling 145 (47%) 125 (50%) Unrelated 156 (51%) 102 (41%) Matched/Mismatched 69/31% 75/24% Median follow-up (months) 19.8 (0.7–229.5) 13 (0.2–210.9)

scholarly journals High Peripheral Blood Stem Cell (PBSC) CD34+ Cell Dose Increases the Risk of Chronic Gvhd after Human Leukocyte Antigen (HLA) Matched Sibling Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5877-5877 ◽  
Author(s):  
Ezzideen Barjes Alrawi ◽  
Erica D. Warlick ◽  
Qing Cao ◽  
Mukta Arora ◽  
Shernan G. Holtan ◽  
...  
Keyword(s):  
Disease Risk ◽  
Conflicts Of Interest ◽  
Risk Index ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Blood Type ◽  
Platelet Recovery ◽  
Cell Dose ◽  
Matched Sibling

Abstract CD34+ cell dose is a critical determinant of outcomes after allogeneic PBSC transplantation, with a CD34 dose ≥2.0 x 10e6/kg shown to positively impact hematopoietic engraftment and survival. However, it is unknown whether additional benefits are observed with even higher CD34 cell doses. Therefore, we further explored the effect of intermediate, high and very high CD34 cell doses on the incidence of engraftment, acute and chronic graft-versus-host disease (GVHD) and transplant related mortality (TRM) and on probability of survival and GVHD-Relapse-free survival (GRFS). Three hundred and five consecutive patients transplanted with GCSF-mobilized PBSC from HLA-matched sibling donors (MSD) were evaluated. Patients were ≥16 years of age, had a hematological malignancy and received a myeloablative or a nonmyeloablative conditioning regimen between 2002 and 2012. The median recipient age was 52 years (r, 19-74 years) with most being male (n=194, 63.8%) diagnosed with leukemia (72%) or lymphoma (22%), and intermediate disease risk index (DRI, n=204, 67%). The median age for the donor were 49 years (r,17-76 years). In 159 patients (52%) the donor and recipient were sex matched with 89 male patients having a female door (29%). The ABO blood type was matched in 195 patients (64%), 153(50%) received a myeloablative (MA) conditioning regimen, and 37 (12%) received a reduce intensity conditioning regimen containing ATG. The median follow up of surviving patients was 793 days (r, 14-4562 days). Patients were divided in four CD34 dose quartiles: first quartile (QT1), ≤4.8 x10e6/kg, QT2 4.8-6.0 x10e6/kg, QT3 6.0-7.5 x10e6/kg, and QT4 ≥ 7.6 x 10e6/kg. Notably, the CD3 doses were similar for all quartiles: QT1 was 3.4 x 10e8/kg (r, 0.3-10.0), QT2 was 2.7 x 10e8/kg (r, 1.1-7.6), QT3 was 2.8 x 10e8/kg (r, 0.8-7.2) and QT4 was 2.8 x 10e8/kg (r, 1.4-7.7); there was no correlation between CD34 and CD3 cell doses. Patient and donor characteristics were similar in the four groups except for shorter median follow-up (P <0.01) in QT1, more sex mismatched grafts (P <0.01) in QT3, and lower median number of cell collections (P <0.01) and more female donor: male recipient pairs (P< 0.01) in QT4. Multivariate analysis results are summarized on the table. Higher CD34+ cell dose was associated with improved platelet recovery with trends toward lower TRM and improved overall survival. Chronic GVHD however was also higher. In summary, additional studies are needed to establish a survival benefit in recipients of higher cell doses >4.8 x 10e6 CD34 cells/kg. Unless survival is positively impacted, the higher risk of chronic GVHD would argue for assigning an upper CD34 cell dose limit to reduce this risk that can significantly impair quality of life. Table Table. Disclosures No relevant conflicts of interest to declare.

scholarly journals Transplantation Outcome By Disease Risk and Donor Type over Time: An Analysis of 100,000 Allogeneic Stem Cell Transplantation on Behalf of the Acute Leukemia Working Party of the EBMT

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 668-668
Author(s):  
Roni Shouval ◽  
Joshua Fein ◽  
Myriam Labopin ◽  
Nicolaus Kröger ◽  
Rafael F Duarte ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Disease Risk ◽  
Disease Status ◽  
Low Risk ◽  
Allogeneic Hsct ◽  
High Risk Disease ◽  
Donor Type ◽  
Unrelated Donors ◽  
Matched Sibling

Abstract Background: Donor type is a key modifiable determinant of outcome following allogeneic hematopoietic stem cell transplantation (HSCT). Utilizing a dataset of more than 100,000 allogeneic transplantations registered with the European Society for Blood and Marrow Transplantation (EBMT), we sought to characterize the evolution of outcomes in transplantation with different donor types across levels of disease-associated risk. Methods: This retrospective study included adult patients treated for hematologic malignancies who underwent first allogeneic HSCT between 2000 and 2015 in EBMT centers. Cord-blood transplantations were excluded, as were patients for whom diagnosis, disease status, or donor relationship were unknown. Missing values were accounted for by multiple imputations. A three-level disease-risk scheme (low, intermediate, and high), was defined by introducing combinations of diagnosis and disease status into a Cox multivariate model for overall survival (OS), similar to the method employed in creating the Disease Risk Index (Armand et al., Blood, 2014). Additional covariates included in the model were reflective of patient, disease, transplant, and center related features. Patients were classified according to a combination of disease risk, donor type, and HSCT year (2000-2005, 2006-2010, 2011-2015). A variable capturing the grouping was introduced into a Cox multivariate analysis adjusted for major transplantation parameters, with the reference category being a matched sibling donor in low-risk disease transplanted between 2011 and 2015. OS was estimated using the Kaplan-Meier method. Competing risk analysis was used to calculate cumulative incidence of non-relapse mortality (NRM) and relapse. Results: A total of 106,086 patients were included in the analysis, with a median age of 48 years (IQR 36-58); Twenty five percent of patients were transplanted between 2000 - 2005, 33% between 2006 and 2010 and 42% between 2011 and 2015. The leading indications for HSCT were acute leukemia (58%), myeloproliferative neoplasms (11%) and non-Hodgkin's lymphomas (10%). Recipients had either HLA matched sibling donors (MSD) (46%), unrelated donors (overall 50%; HLA matched 10/10 (MUD) [20%], mismatched HLA 9/10 (MMUD) [6%], mismatched HLA&lt;9/10 [2%], imputed HLA match [21%]) or haploidentical (Haplo) (4%) donors. Graft source was primarily peripheral blood (81%). Myeloablative conditioning was used in 53% of cases. The median follow-up was 3.6 years (95% CI 3.5-3.6). The risk of overall mortality varied depending on the combination of donor type, disease risk and transplantation year (figure A). In low and intermediate risk disease, a matched sibling donor had the most favorable outcome across year-periods. However, in high-risk disease, overlapping hazard ratios (HRs) were observed between MSD and MUD in 2011-2015 (2.8 [2.6-3.0] versus 3.0 [2.8-3.2], respectively). The cumulative incidence for NRM for MSD vs. MUD in high-risk disease transplanted from 2011-2015 was 26.1% (23.8-28.6) vs. 35.3% (32.6-38.3, p &lt; 0.0001), respectively. Similarly, relapse incidence was 50.7% (48.0-53.6) vs. 41.0% (38.3-44.0, p &lt; 0.0001). In high disease risk, the risk for mortality has decreased over the years for MSD and MUD, and even more so for transplantations from Haplo donors (2000-2005 HR 5.11 [4.3-6.1]; 2011-2015 HR 3.9 [3.5-4.3]). In the low-risk setting, transplantations from Haplo donors had a comparable risk to MSD and MUD (2011-2015 Low risk: MSD reference, MUD 1.2 [1.1-1.3], Haplo 1.3 [1.2-1.5]). A representative example is seen in Figure B: the probability of 2-year overall survival between 2011-2015, low risk in MSD was 66.5% (95% CI 65.0-68.0), MUD 63.4% (61.7-65.1), and Haplo 60.4 (56.9-64.1). Conclusion: Survival has improved following allogeneic HSCT over the past two decades. This improvement is especially clear in the case of haploidentical donors, though MSD and MUD are still associated with better outcomes. In high-risk disease, the risk of mortality is equivalent between matched sibling and matched unrelated donors. Notably, the probability for NRM is higher with MUD, but relapse incidence is lower, emphasizing the importance of graft-versus-tumor effect in the high-risk setting and the ongoing need for NRM reduction strategies. Disclosures Kröger: Janssen Global Services, LLC: Speakers Bureau; Amgen Inc.: Speakers Bureau; Novartis AG: Research Funding; RIEMSER Pharma: Research Funding; Neovii Pharmaceuticals AG: Speakers Bureau; Novartis AG: Speakers Bureau; Sanofi: Speakers Bureau. Bader: Novartis, Medac, Amgen, Riemser, Neovii: Consultancy, Honoraria, Research Funding. Kuball: Miltenyi: Research Funding; Gadeta (www.gadeta.nl): Consultancy, Equity Ownership, Patents & Royalties: on gdT cells and receptors and isolation strategies , Research Funding. Snowden: Sanofi: Honoraria. Mohty: Sanofi: Honoraria, Speakers Bureau.

scholarly journals Total Body Irradiation for Hematopoietic Stem Cell Transplantation: What Can We Agree on?

2021 ◽  
Vol 28 (1) ◽  
pp. 903-917
Author(s):  
Mitchell Sabloff ◽  
Steven Tisseverasinghe ◽  
Mustafa Ege Babadagli ◽  
Rajiv Samant
Keyword(s):  
Cell Transplantation ◽  
Total Body Irradiation ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Late Toxicity ◽  
Hepatic Function ◽  
Vascular Supply ◽  
Entire Body ◽  
Hematopoietic Stem ◽  
Total Body

Total body irradiation (TBI), used as part of the conditioning regimen prior to allogeneic and autologous hematopoietic cell transplantation, is the delivery of a relatively homogeneous dose of radiation to the entire body. TBI has a dual role, being cytotoxic and immunosuppressive. This allows it to eliminate disease and create “space” in the marrow while also impairing the immune system from rejecting the foreign donor cells being transplanted. Advantages that TBI may have over chemotherapy alone are that it may achieve greater tumour cytotoxicity and better tissue penetration than chemotherapy as its delivery is independent of vascular supply and physiologic barriers such as renal and hepatic function. Therefore, the so-called “sanctuary” sites such as the central nervous system (CNS), testes, and orbits or other sites with limited blood supply are not off-limits to radiation. Nevertheless, TBI is hampered by challenging logistics of administration, coordination between hematology and radiation oncology departments, increased rates of acute treatment-related morbidity and mortality along with late toxicity to other tissues. Newer technologies and a better understanding of the biology and physics of TBI has allowed the field to develop novel delivery systems which may help to deliver radiation more safely while maintaining its efficacy. However, continued research and collaboration are needed to determine the best approaches for the use of TBI in the future.

scholarly journals Total body irradiation in a case of thalassemia major with source to axis distance based planning: A case report

2020 ◽  
pp. 25-28
Author(s):  
Mayuresh D. Virkar ◽  
Rajkumar Chauhan ◽  
Pranav Chadha ◽  
Kaustav Talapatra ◽  
Reuben Jake Rodrigues ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Total Body Irradiation ◽  
Conditioning Regimen ◽  
Thalassemia Major ◽  
Entire Body ◽  
Hematopoietic Stem ◽  
Total Body

Background: The use of total body radiation (TBI) before hematopoietic stem cell transplantation (HSCT) would increase the engraftment without transplant-related morbidity or mortality among Thalassemia major (TM) cases. Case presentation: A 2-year-old female child, diagnosed with TM was scheduled for haploidentical allogenic transplant-based protocol, and after that, based on protocol she was scheduled to undergo a single session of TBI as a conditioning regimen before haploidentical allogenic hematopoietic stem cell tranplant. A total dose of 4 Gy was administered.. The incidence of graft failure was reduced as TBI was used before allogeneic stem cell transplantation. TBI provided a uniform dose of radiation to the entire body, penetrating areas such as the central nervous system (CNS) and testes. Conclusion: Total Body Irradiation with the SAD technique is the most effective way of treatment. As it is comfortable for the patient to undergo, easily reproducible, and it helps to achieve a uniform dose distribution.

Sign in / Sign up

Export Citation Format

Share Document