Successful Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Mild Renal Dysfunction Calculated By Creatinin Clearance

Abstract Introduction: The creatinine clearance rate (Ccr) is a more accurate indicator of renal function than serum creatinine. There remains a paucity date of prognostic value of mild to severe renal impairment calculated by Ccr for patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Herein, we evaluated the transplant outcome of patients with mild to severe renal dysfunction and compared to those without renal dysfunction. Patients and methods: A total of 186 patients (118 male and 68 female; median age, 50 years; range 15-70 years) with hematological malignancies who underwent first allo-HSCT in our institution between 2008 and 2015 were retrospectively collected from medical records. Transplant outcomes were compared with regard to renal function before allo-HSCT. The threshold of renal dysfunction was 60 ml/min (Ccr < 60) calculated by Ccr. Overall survival (OS) was estimated by Kaplan-Meiyer. Engraftment rate, cumulative incidence of relapse (CIR), non-relapse mortality (NRM), acute graft-versus-host disease (aGVHD), chronic GVHD and acute kidney injury (AKI) within 100 days after alo-HSCT were calculated using Grayfs method. Factors associated with significance (p < 0.1) on univariate analyses were subjected to multivariate analysis. Multivariate analysis was performed using the Cox proportional hazards regression model for OS and Fine-gray proportional hazard regression model for NRM and CIR. Results: Among the 186 patients, renal dysfunction (Ccr < 60) was observed in 30 patients (16%) before conditioning regimen. We observed no significant difference between Ccr < 60 group and Ccr ≥ 60 group in terms of clinical characteristics including gender, HLA disparity, stem cell source, disease risk, comorbidity, performance status at allo-HSCT and GVHD prophylaxis. However, compared to Ccr ≥ 60 group, patients with Ccr < 60 group were significantly older (p = 0.0008), lower estimated GFR (p < 0.0001), higher serum creatinine (p < 0.0001), more cases diagnosed non-Hodgkin lymphoma (p = 0.0003) and more cases received reduced intensity conditioning regimen (p = 0.002). All but one patient with CCr < 60 group achieved neutrophil engraftment median 15 days (range, 9-24) after transplantation (engraftment rate 97%) and 1 patient died before engraftment. Regarding the transplantation outcome, no significant difference was observed in OS, CIR, NRM, aGVHD, cGVHD and AKI after allo-HSCT between 2 groups (Ccr < 60 vs. CCr ≥ 60; 2-year OS, 45% vs. 49%, p = 0.6, 2-year CIR, 41% vs. 30%, p = 0.3, 2-year NRM, 23% vs. 26%, p = 0.6, day-100 AKI, 57% vs. 63%, p = 0.6, Figure 1). Multivariate analysis demonstrated that Ccr < 60 before allo-HSCT was not an independent prognostic factor for OS, CIR and NRM (Table 1). To investigate the impact of mild to severe renal failure on the transplant outcome, we next explored the clinical results of 30 patients with renal failure more in detail. Of them, 13 patients (43%) had estimated GFR < 60 ml/min/1.73m2 and only 5 patients (17%) had a serum creatinine level > 1.2mg/dl. Two patients (7%) developed end-stage renal failure requiring dialysis. Eighteen patients (60%) died at a median 194.5 (range, 15-859) days after allo-HSCT. Relapse of the primary disease was the leading cause of death (n=9) and cause of NRM were infection (n=3), veno-occlusive disease (n=2), respiratory failure (n=2), cGVHD (n=1) and central nervous system complication (n=1). No patients died from renal failure. All patients with severe renal dysfunction defined as Ccr < 40ml/min (Ccr; 13.4 ml/min, 36 ml/min and 36 ml/min) died 17, 15 and 72 days after allo-HSCT, respectively. Conclusion: Our cohorts with total 186 patients underwent allo-HSCT showed that mild renal dysfunction defined as Ccr < 60 ml/min before allo-HSCT did not affect adversely for transplant outcomes. In line with previous reports, Ccr could detect renal impairment that could not identified by GFR estimated from serum creatinin. On the other hand, no patients with severe renal dysfunction could survive after allo-HSCT. To our knowledge, the current study includes the largest number of patients with Ccr < 60ml/min. However, our small experience clearly desires larger series patients for evaluating the real impact of mild to severe renal dysfunction before transplantation. Disclosures No relevant conflicts of interest to declare.

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The Role of Stem Cell Mobilization Regimen on Lymphocyte Collection Yield and Survival after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma.

Blood ◽

10.1182/blood.v106.11.1174.1174 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1174-1174 ◽

Cited By ~ 1

Author(s):

Luis F. Porrata ◽

Suzanne R. Hayman ◽

Morie A. Gertz ◽

Martha Q. Lacy ◽

Angela Dispenzieri ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

Peripheral Blood ◽

Plasma Cells ◽

Conditioning Regimen ◽

Stem Cell Mobilization ◽

Cell Labeling ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Cell Mobilization

Abstract We previously have reported that autograft absolute lymphocyte count (A-ALC) is a possible prognostic factor for survival after autologous peripheral blood stem cell transplant (ASCT) for myeloma (MM). Factors affecting A-ALC in MM are unknown. We hypothesize that method of stem cell mobilization, hematopoietic growth factor (HGF) vs. HGF+Cytoxan chemotherapy (C+HGF), directly affects A-ALC collection. 191 consecutive MM patients between 1994 and 2004 were analyzed retrospectively. Patients generally were mobilized with C+HGF prior to 2003. Thereafter, C+HGF was reserved largely for those with ≥4% circulating peripheral blood plasma cells (PC), a negative prognostic indicator. No patients were transplanted in disease relapse or refractory disease. Patients also were matched for age, sex, β2-microglobulin, conventional cytogenetics, LDH, c-reactive protein, number of prior therapies, plasma cell labeling index (PCLI), pre-mobilization ALC, and % bone marrow (BM) PC. The groups HGF (n=80) and C+HGF (n=111) differed with respect to the conditioning regimen (p < 0.0001), and presence of (≥4%) circulating peripheral blood PC (p<0.005). The primary end-point of the study was to assess the correlation between HGF vs C+HGF, and A-ALC. The secondary endpoint was to determine if HGF vs C+HGF affected survival post-ASCT. Patients mobilized with HGF had a higher A-ALC compared to those mobilized with C+HGF [0.764 x 109 lymphocytes/kg (range: 0.146–1.803) vs. 0.212 (range: 0.016–1.26), p<0.0001]. No association was identified between A-ALC and conditioning regimens (p = 0.19) and PC (p = 0.31). Median overall survival (OS) and progression-free survival (PFS) were longer in those mobilized with HGF vs. C+HGF (not reached vs. 48 months, p<0.0150; not reached vs. 21 months, p<0.007, respectively). Multivariate analysis demonstrated that age ≥50 vs age ≤50 (p<0.05) and A-ALC ≥0.5 vs <0.5x109 lymphocytes/kg (p<0.0397) were independent predictors of OS. Factors influencing PFS in the multivariate analysis included circulating PC ≥4% vs <4% (p<0.0157), PCLI ≥ 1% vs PCLI ≤ 1% (p<0.0107), and A-ALC ≥0.5 vs <0.5x109 lymphocytes/kg (p<0.0042). On multivariate analysis, the method of stem cell mobilization and the conditioning regimen did not have a statistically significant effect on either OS or PFS. We hypothesize that the differences in PFS and OS seen between the HGF vs C+HGF mobilization groups are mediated through the A-ALC. These data suggest that mobilization regimens should not only collect CD34+ stem cells, but also be optimized to collect an A-ALC target which may impact on PFS and OS post-ASCT.

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

Blood ◽

10.1182/blood.v118.21.4576.4576 ◽

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.

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

Blood ◽

10.1182/blood.v114.22.3306.3306 ◽

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.

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Cyclophosphamide Followed By Busulphan in Place of Standard BuCy Regimen for Patients Undergoing Allogeneic Stem Cell Transplantation: A Preliminary Experience from a Single Centre in India

Blood ◽

10.1182/blood.v124.21.5856.5856 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5856-5856

Author(s):

Sainath Bhethanabhotla ◽

Ranjit Kumar Sahoo ◽

Lalit Kumar ◽

Atul Sharma ◽

Sameer Bakhshi

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Conditioning Regimen ◽

P Value ◽

Cell Transplant ◽

Toxicity Profile ◽

Hematopoietic Stem ◽

Significant Difference ◽

Baseline Characteristics

Abstract Conditioning regimens are an important issue determining the outcome of hematopoietic stem cell transplantation (HSCT). Altering the administration order of Busulphan (Bu) and Cyclophosphamide (Cy) during conditioning from conventional method of administering Bu followed by Cy had resulted in an improved toxicity profile in few animal and subsequent human studies. However the data substantiating this approach is limited. We retrospectively analyzed all consecutive patients receiving allogeneic stem cell transplant (Allo SCT) with myeloablative conditioning from 2009 to 2013. A total of 40 patient received Allo SCT of which 18 patient received Bu-Cy and 22 patients received Cy-Bu conditioning regimen. The Bu–Cy conditioning regimen consisted of i.v. Bu 0.8 mg/kg administered every 6 h (16 doses) on days −7 to −4, followed by i.v. Cy 60 mg/kg on days −3 and −2. Patients with the Cy–Bu regimen received i.v. Cy 60 mg/kg on days −7 and −6; followed by i.v. Bu 0.8 mg/kg administered every 6 hr (16 doses) on days −5 to −2. GVHD prophylaxis was given with Cyclosporine A and methotrexate. Common Terminology Criteria for Adverse Events version 3.0 (CTCAE) was used for assessment of toxicity. The diagnosis of sinusoidal obstruction syndrome (SOS) was based on modified Seattle criteria. Pre-transplant characteristics were comparable in the two cohorts (Table 1a and 1b). Time to platelet engraftment was earlier in the Cy-Bu cohort (21 days vs. 16 days; P=0.008) (Table 2).Treatment related side effects were similar in both the groups except hepatotoxicity which was higher in Bu-Cy as compared to Cy-Bu group (10 (55.16%) vs. 3 (13.64%); p=0.03). There was no significant difference in treatment related mortality (TRM) at day 100; however there was trend towards higher TRM at day 30 in Bu-Cy group (3 vs. none; p=0.083).There was no difference in aGVHD incidence, grade or stage of organ involved between the 2 groups. As in previous studies hepatotoxicity in the present analysis was found to be less in patients who received Cy-Bu as the conditioning regimen and there was earlier platelet engraftment in this group. These findings suggest Cy-Bu has better toxicity profile than conventional Bu-Cy regimen. However further prospective studies are required to confirm these findings. Table 1a. Baseline Characteristics Patient Characteristics Bu-Cy (n=18) Cy-Bu (n=22) P value Sex Male 15 16 0.424 Age (in yrs) Median (Range) 17 (1-50) 16 (1-48) ≤18 9 13 ≥18 9 9 Underlying Disease AML 14 12 0.415 ALL 3 4 CML 1 3 MDS 0 2 Primary Myelofibrosis 0 1 Pre-transplant Remission Status CR 11 11 0.482 Performance status (ECOG) 0 4 3 0.314 1 9 16 HSCT Comorbidity Index 0 14 15 0.341 1 1 5 2 2 2 3 1 0 Table1b. Baseline Characteristics Transplant characteristics Bu-Cy Cy-Bu P value Time from diagnosis to Transplant Mean (days) + SD 548.1 675 0.567 HLA Matching HLA identical (6/6) 17 21 0.884 HLA mismatch (5/6) 1 1 Donor Matched Sibling 17 16 0.884 UCB 1 1 Donor Age Median(Range) 20 (0-47) 16 (0-50) 0.781 Donor Sex Male 5 14 0.034 Female 12 8 Sex mismatch 12 13 0.458 Female Donor in Male patient 11 7 0.064 Harvest Source Peripheral Blood (PB) 15 21 0.269 Bone Marrow (BM) 2 0 Cord Blood (UCB) 1 1 CD 34 Count(x106 cells/kg) Mean+SD 5.12+2.60 5.66+2.37 0.499 CD 3 Count(x107 cells/kg) Mean 25.5 17.5 0.200 Table 2 Results Outcome Bu-Cy Cy-Bu P ANC recovery 14 (11-30) 11 (8-32) 0.119 Platelet recovery 21 (17-44) 16 (11-27) 0.008 Platelets transfused 6 (1-10) 4 (1-15) 0.166 Days of GCSF 18 (12-36) 14 (9-37) 0.126 D100 Complete Donor Chimerism 9 (90%) 12(85.71%) 1.000 Transplant Response 15/17 (88.24%) 19/22 (86.36%) 1.000 Days of Antimicrobial use 13 (0-34) 13 (0-36) 0.83 Hepatotoxicity (grade3-4) 10/18 (55.56%) 3/22 (13.64%) 0.030 Nephrotoxicity (grade3-4) 3/18 (16.67%) 1/22 (4.55%) 0.204 Mucositis (grade3-4) 6/18 (33.33%) 6/22 (27.27%) 0.677 Any Grade 3-4 toxicity 10/18 (55.56%) 9/22 (40.91%) 0.356 D30 TRM 3 (16.67%) 0 0.083 D100 TRM 4 (22.22%) 2 (10%) 0.395 Follow up 28.67 months 7.6 months Acute GVHD 3/18 (16.67%) 5/22 (22.73%) 0.709 Disclosures No relevant conflicts of interest to declare.

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Outcomes in Allogeneic Hematopoietic Stem Cell Transplant Patients ≥ 60 Years of Age with a Novel Reduced Intensity Conditioning Regimen Incorporating Extracorporeal Photopheresis,

Blood ◽

10.1182/blood.v118.21.4153.4153 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4153-4153

Author(s):

Furha I. Cossor ◽

Sandy Wong ◽

Kenneth B Miller ◽

Deborah Black ◽

Raymond L. Comenzo ◽

...

Keyword(s):

Stem Cell ◽

Board Of Directors ◽

Research Funding ◽

Conditioning Regimen ◽

Extracorporeal Photopheresis ◽

Advisory Committees ◽

Hematopoietic Stem ◽

Significant Difference ◽

Blood Stem Cells ◽

Grade Ii

Abstract Abstract 4153 The optimal preparative regimen for older patients undergoing hematopoietic stem cell transplantation (HSCT) is unclear. We routinely employ a reduced intensity conditioning regimen consisting of extracorporeal photopheresis (ECP) on days −6 and −5, Pentostatin 4 mg/m2/day by continuous infusion on days −4 and −3, and 600 cGy total body irradiation in 3 divided fractions on days −2 and −1 (“PPT regimen”) for patients greater than 60 years of age (Bone Marrow Transp 2004; 33:881). We now report outcomes of 38 consecutive patients ≥ 60 years old (median 62, range 60–70) (M 22, F 16) transplanted at our center between 1/1/00 and 4/1/11 for hematologic malignancies: AML (n=23), MDS (n=10), ALL (n=1), CLL (n=1), NHL (n=2) and MM (n=1). Twenty-six (68.4%) received matched related and 12 (31.6%) 6/6 matched unrelated donor (MUD) grafts. Twenty-five (65.8%) received marrow and 13 (34.2%) peripheral blood stem cell grafts. Median time to neutrophil engraftment was 16 days (3–25). Survival at day 100 was 84% (32/38), with a 13% TRM (5/38) and 3% (1/38) incidence of relapse-related death. Actuarial 1-year overall survival (OS) for all patients was 45% (95% CI 28 – 61%), and median OS in all patients was 10.6 months (95% CI 4.6 – 25.7 months). Estimated 1-year event-free survival, defined as freedom from relapse, progression, or death from any cause, was 44% (95% CI 27 – 59%). Median event-free survival for the entire cohort was 7 months (95% CI 3.6 – 25.6 months). Grade II and grades III/IV acute GvHD (aGvHD) occurred in 8 (21%) and 2 (5%) patients respectively within 1 to 8 weeks of HSCT (median 16 days). After day 100, 6 patients had died, 1 was missing data, and 23 (74% of remaining patients and 60% of the original cohort) had symptoms of GvHD. Fourteen met NIH consensus criteria for chronic GvHD (cGvHD) including 6 with severe classic or overlap cGvHD while 6 had recurrent, 2 persistent and 1 delayed aGvHD. Of those with aGvHD after day 100, 2 patients exhibited ≥ grade III disease. Median time to onset of cGvHD was 4.1 months (3.3 – 11.7). Among patients who received marrow as their stem cell source (n=25), incidence of grades II-IV aGvHD was 32% (24% grade II, 8% grade III/IV), and incidence of any GvHD from day 100 up to date of death or last follow-up was 68%. Among those who received blood stem cells (n=13) incidence of grades II-IV aGvHD was 15% (all grade II) and incidence of GvHD from day 100 until date of death or last follow-up was 83%. There was no statistically significant difference between those who received marrow versus blood stem cells with respect to incidence of either grade II-IV aGvHD or GvHD after day 100 (P =0.27 and 0.36). For those who received MUD transplants (n=12), incidence of grades II-IV aGvHD and of any post-day 100 GvHD were 42% (33% grade II, 8% grade IV) and 75% respectively, and in those who received related donor transplants (n=26) were 19% (15% grade II, 4% grade IV) and 74%, respectively. There was no statistically significant difference between MUD HSCT versus related donor HSCT patients with regard to grade II-IV aGvHD or GvHD after day 100 (P =0.14 and 0.94). In conclusion, our approach was well tolerated by HSCT patients > 60 years old, provided prompt myeloid recovery and had an acceptable incidence of post-day 100 severe chronic (19%) or > grade II late acute GvHD (6%). Disclosures: Off Label Use: Pentostatin and Extracorporeal photopheresis are not FDA approved for conditioning prior to allogeneic transplant. Comenzo:Elan: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Neotope: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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Influence of Stem Cell Source On GvH and NRM: Comparison of 10/10 HLA-Matched Unrelated Donor (MUD) with 9/10 HLA-Mismatched Unrelated Donor (MMUD) and Unrelated Cord Blood (UCB) Transplants.

Blood ◽

10.1182/blood.v120.21.3135.3135 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3135-3135

Author(s):

Clémence Granier ◽

Emeline Masson ◽

Lucie Biard ◽

Raphael Porcher ◽

Regis Peffault de la Tour ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Hla Typing ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Stem Cell Source ◽

Significant Difference ◽

Cell Source

Abstract Abstract 3135 Background: When an HLA-matched donor is not available for allogeneic Hematopoietic Stem Cell Transplantation (HSCT), the use of an alternative HLA-mismatched stem cell source may be considered. In Europe, HLA compatibility for HSCT is calculated for 10 alleles (HLA-A, -B, -C, -DRB1, -DQB1). The aim of this study was to retrospectively compare outcomes after transplantation from 10/10 HLA-MUD, 9/10 HLA-MMUD and UCB performed at the Hospital Saint Louis (Paris, Fr). Methods: Patients receiving a first allogeneic transplantation from a 10/10, 9/10 UD or UCB from 2000 to 2011 were included. High resolution HLA typing was performed by PCR SSO and SSP for HLA loci: A, B, C, DRB1 and DQB1. The following variables were studied as risk factors for transplant outcomes: disease, disease risk (standard/high risk), age at transplant, gender, donor/recipient sex-matching, ABO matching, donor/recipient CMV status, conditioning regimen, and use of anti-thymoglobulin (ATG). Results: 355 consecutive patients with hematologic malignancies were analyzed. One hundred and ninety-six were transplanted with MUD, 84 with MMUD (mismatches for HLA-A: 16%, -B: 16%, -C: 39%, -DRB1: 8%, -DQB1: 21%) and 75 with UCB (52% with single and 48% with two UCB unit; 87% of all UCB transplants were 4–6/6 HLA-matched). Median patient age was 31 (range: 5–55). Patient characteristics differed between the 3 groups: (i) median age at transplant: 36 in MUD, 31 in MMUD, 22 in UCB (p<0.0001), (ii) high risk disease: 37%, 51%, 68% (p<0.0001), (iii) CMV negative donor/positive recipient: 31%, 36%, 60% (p<0.0001), (iv) use of ATG: 37%, 64%, 55% (p<0.0001). Cumulative incidences of grade II-IV and grade III-IV acute GvHD disease (aGvHD) were 61% (66% for MUD, 60% for MMUD and 48% for UCB) and 17% (17%, 24% and 15%), respectively. Three-year cumulative incidence of chronic GvHD (cGvHD) was 46% (51% for MUD, 49% for MMUD and 29% for UCB). Three-year NRM was 34% (28% for MUD, 31% for MMUD and 51% for UCB). Graft failure occurred in 15% of UCB patient, 8% in MMUD group and 3% in MUD group (significant difference between UCB and MUD: OR=5.44, 95%CI 1.93–15.3, p=0.001). Multivariate analysis is summarized in table 1. It showed that MMUD tented to have a higher incidence of aGvHD III-IV than MUD and UCB. UCB had a lower incidence of cGvHD than MMUD. No significant effect of HSCT source on NRM was demonstrated. Conclusion: Compared to MMUD, UCB-HSCT induces less cGvHD and non significantly increased NRM. Compared to MUD, MMUD and UCB-HSCT did not result in a clear increase of NRM. UCB and 9/10 HLA-MMUD are both suitable stem cell sources for patients who cannot benefit from 10/10 HLA-MUD transplant. Disclosures: No relevant conflicts of interest to declare.

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Impacts of Total Body Irradiation in Allogeneic Umbilical Cord Blood Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood-2021-152893 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4852-4852

Author(s):

Jeffrey J. Pu ◽

Kristin N. Berger ◽

Hao Wang ◽

Wei Fu ◽

Elizabeth L Miller ◽

...

Keyword(s):

Stem Cell ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Conditioning Regimen ◽

Hematopoietic Stem ◽

Significant Difference ◽

Conditioning Regimens ◽

Total Body ◽

Univariate Analyses

Abstract Background: Umbilical cord blood hematopoietic stem cell transplant (UCBT) has been practiced as an alternative source of hematopoietic stem cells for patients in need of transplantation. Double-units UCBT has been established as a means of achieving a cell dose of at least 2.5x10 7 nucleated cells per kilogram of body weight in adult recipients. The advantages of UCBT include its rapid availability, reduced stringency in terms of human leukocyte antigen (HLA) match requirements, and subsequent increase in access to transplants for racial minorities. Both related and unrelated UCBTs with single or double units have been performed with high rates of success in both pediatric and adult settings to treat a variety of medical conditions. Prior to undergoing UCBT, recipients must undergo a conditioning regimen to create space in the bone marrow, suppress the immune system to allow for donor stem cell engraftment, and reduce the tumor burden in cases of neoplastic disease. Total body irradiation (TBI) is commonly incorporated into conditioning regimens to enforce these efforts. Although intense myeloablation in general is associated with a lower risk of relapse and graft rejection, greater regimen intensity also leads to a higher rate of transplant related morbidity and mortality (TRM). Inclusion of TBI specifically in conditioning regimens has been shown to result in organ toxicity and subsequent malignant neoplasm. To help mitigate the risks of myeloablative conditioning (MAC) regimens, non-TBI and reduced-intensity conditioning (RIC) regimens have been investigated as a means of reducing TRM and increasing access of transplantation to patients with age disadvantages or significant comorbidities. Despite ongoing investigation, studies comparing conditioning regimens of UCBT, with and without TBI, remain limited. This study, using real-world data collected from 4 institutions, retrospectively analyzed the impact of TBI as part of MAC or RIC conditioning regimens in patients undergoing UCBT. Methods: This is a retrospective study that analyzed the outcomes of 136 patients receiving umbilical cord blood transplants at four institutions. Seventy-nine patients received myeloablative condition (MAC), in which 36 underwent TBI and 33 did not; 67 patients received reduced-intensity condition (RIC), in which 24 underwent TBI and 43 did not. Univariate and multivariate analyses were conducted to compare the outcomes and the post-transplant complications between patients who did and did not undergo TBI in MAC subgroup and RIC subgroup, respectively. Results: Characteristics of UCBT recipients who did and did not undergo TBI, stratified by conditioning regimen were compared with both multivariate and univariate analyses and didn't see significant difference. We didn't observe significant difference in GVHD and transplant-related infection incidence rates between patient subgroup that did and did not undergo TBI as part of their pre-UCBT conditioning regimen via both multivariate and univariate analyses. In RIC subgroup, the patients who underwent TBI appeared to have superior overall survival (adjusted hazard ratio [aHR]=0.25, 95% confidence interval [CI]: 0.09-0.66, p=0.005) (Figure 1), progression-free survival (aHR=0.26, 95% CI: 0.10-0.66, p=0.005) (Figure 2), and shorter time to neutrophil engraftment (aHR=6.26, 95% CI: 2.27 - 17.31, p=0.0004) (Figure 3). However, in MAC subgroup, there were no statistically significant difference between using and not using TBI. There were also no differences between the patients who either underwent or not underwent TBI in terms of acute or chronic GVHD rates or rates of transplant-related infections in both subgroups. Conclusion: Combining with RIC, TBI may improve OS, PFS, and neutrophil engraftment time. However, the incidences of other post-transplant complication were comparable between patients who underwent and did not undergo TBI as part of conditioning regimens during umbilical cord blood transplant. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Results of a Phase I/II Study of Gemtuzumab Ozogamicin Added to Fludarabine (F), Melphalan (M) and Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Relapsed Myeloid Leukemias.

Blood ◽

10.1182/blood.v106.11.841.841 ◽

2005 ◽

Vol 106 (11) ◽

pp. 841-841 ◽

Cited By ~ 1

Author(s):

Marcos de Lima ◽

S. Giralt ◽

Z. Caldera ◽

G. McCormick ◽

M. Qazilbash ◽

...

Keyword(s):

Bone Marrow ◽

Renal Failure ◽

Stem Cell ◽

Blast Crisis ◽

Conditioning Regimen ◽

Control Group ◽

High Dose ◽

Hematopoietic Stem ◽

Myeloid Leukemias ◽

Active Disease

Abstract Most patients (pts) transplanted with active myeloid leukemias will relapse after HSCT. Intensity of the conditioning regimen is an important component of disease control. We hypothesized that GO could safely increase the anti-disease activity of FM, and investigated this hypothesis in the trial reported here. Patients and Methods: Objective: to determine the dose of GO with the lowest toxicity (tox), and the highest response probabilities. Tox: grade 3–4 organ tox, engraftment failure or early death (ED; first 30 days post HSCT). Response was defined as no tox, engraftment, and remission (CR) on day +30. Trial was designed with GO doses of 4, 6 and 9 mg/m2 but given tox observed at 4mg/m2, doses 6 and 9 mg/m2 were not used and dose 2mg/m2 was added. Eligible were pts aged 12–75 years, not candidates for high-dose regimens or with high-risk CD33+ disease. Treatment: GO 2 or 4mg/m2 day -12, F 30mg/m2 (days -5 to -2), M 140mg/m2 (day -2); HSCT day zero. ATG was added in unrelated (UD) HSCT. Graft-versus-host disease (GVHD) prophylaxis: tacrolimus and mini-methotrexate (5mg/m2 day+1,+3,+6,+11). GO was given on day -12 to minimize probability of delaying engraftment. We treated 52 pts, median age 53 yrs (13–72), with AML (n=47), MDS (n=4) or blast crisis CML(n=1). Disease status at HSCT: CR (n=3),induction failure (n=15), first/second relapse (n=33), untreated MDS (n=1). 18 pts had a previous HSCT (allogeneic, n=11 or autologous, n=7). At study entry, median number of bone marrow blasts was 17% (0–95%); 33% of the pts had circulating blasts, 4 pts were FLT3 positive and 38% had poor prognosis cytogenetics. Median blast CD33 expression: 89% (22.5–99.6). Donors: related (n=33) or UD (n=19). Stem cell source was peripheral blood (n=43) or bone marrow (n=9). Results: Median day 30 donor cell chimerism was 100%. Median time to ANC> 500/mm3 was 13 days. Eight pts received GO at 4 mg/m2; 2 died early (due to pneumonia and renal failure) and 2 developed gd III gastro-intestinal and renal tox. 44 pts were then treated at 2 mg/m2: 3 pts died of regimen-related tox (2 ED due to pulmonary bleeding and sepsis, and 1 death within the first 100 days due to pneumonia, renal failure/TTP/HUS). 100-day treatment-related mortality (including 2 deaths due to aGVHD and 1 due to infection) was 15% (n=8). Tox included reversible gd III-IV bilirubin (n=2), transaminase elevation (n=5), moderate hepatic VOD (n=1) and gd I-II GI tract (n=39). CR rate was 90%; 1 pt failed to respond. Gd II-IV and III-IV aGVHD rates were 44% and 23%, respectively, and 58% developed cGVHD. Median follow-up is 9 months (2.5–36) for surviving pts (n=29); 17 pts have relapsed. Median event-free-survival (EFS) is 3.8 mos. Median EFS of a historic control group treated with FM140 (n=36) was 2.2 mos (Figure). Tox of GOFM is similar to that documented by our group with FM140 mg/m2 in a somewhat better prognosis population.(de Lima et al. Blood.2004; 104:865–72) Conclusion: GO 2mg/m2 can be safely added to FM, and may improve the anti-leukemic efficacy of the regimen. EFS - patients with active disease at HSCT EFS - patients with active disease at HSCT

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Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Adult Patients with T-Cell Acute Lymphoblastic Leukemia: A Survey From the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽

10.1182/blood.v120.21.356.356 ◽

2012 ◽

Vol 120 (21) ◽

pp. 356-356

Author(s):

Xavier Cahu ◽

Myriam Labopin ◽

Sebastian Giebel ◽

Gerard Socie ◽

Dietrich Beelen ◽

...

Keyword(s):

Multivariate Analysis ◽

Stem Cell ◽

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Univariate Analysis ◽

Conditioning Regimen ◽

Myeloablative Conditioning ◽

Hematopoietic Stem ◽

Donor Type ◽

Cell Acute Lymphoblastic Leukemia

Abstract Abstract 356 Background: T-cell acute lymphoblastic leukemia (T-ALL) comprises about 25% of all adult ALL. Although allogeneic hematopoietic stem cell transplantation (allo-SCT) exerts a graft versus leukemia effect, very few large series exist on the outcome of adult T-ALL patients allografted with a myeloablative conditioning regimen. Patients and methods: adult cases of T-ALL patients who underwent related or unrelated (6/6) allo-SCT with a myeloablative regimen between 2000 and 2010 were extracted from the EBMT registry. Patients with a prior autologous or allogeneic SCT and those who received cord blood allo-SCT were excluded from analysis. Primary goal of the study was to evaluate overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and relapse incidence (RI) for T-ALL patients in first (CR1), second or subsequent remission (CR2+) and in relapse or refractory disease (advanced). Results: 886 patients were included in this study. The median follow-up was 43 months. The median age was 29 (range: 18–63) and 649 patients (73%) were males. Allo-SCT characteristics are described in table 1. Among patients (n=561) allografted in CR1, 25% had a white blood cell count (WBC) ≥100 G/L, and a complex karyotype was identified in 43 cases (16%, available data = 268). 4-year OS and 4-year LFS were 58% (standard deviation (SD) 2%) and 55% (SD 2%), respectively, whereas 4-year NRM and RI were 19% (SD 2%) and 26% (SD 2%), respectively. In univariate analysis, age < median age (60% versus 50%, p = 0.02) and use of total-body-irradiation (TBI) (57% versus 42%, p = 0.04) were associated with an improved 4-year LFS. In a multivariate analysis including age, use of TBI, donor type and donor sex, age <median age (Hazard Ratio (HR)= 0.71 [95% CI: 0.55–0.92], p=0.01) and use of TBI (HR = 0.67 [0.48–0.93], p=0.02) were associated with an improved LFS. In the CR2+ T-ALL group (n=151), 4-year OS and 4-year LFS were 25% (SD 4%) and 24% (SD 4%), respectively. 4-year NRM was 27% (SD 4%) whereas 4-year RI was 49% (SD 4%). In univariate analysis, use of TBI was associated with an improved 4-year LFS (29% versus 8%, p = 0.02). In a multivariate analysis including age, patient sex, use of TBI and donor type, use of TBI was associated with an improved LFS (HR = 0.57 [0.37–0.88], p=0.01). Finally, in the advanced T-ALL group (n=174), 4-year OS and 4-year LFS were 15% (SD 3%) and 12% (SD 3%), respectively. 4-year NRM was 30% (SD 4%), whereas 4-year RI was 58% (SD 4%). In univariate analysis, use of TBI was associated with an improved 4-year LFS (16% versus 3%, p= 0.002). In a multivariate analysis including age, use of TBI and donor type, use of TBI was again associated with an improved LFS (HR=0.56 [0.38–0.82], p=0.003). Conclusion: This large series demonstrates that myeloablative conditioning allo-SCT is followed by a relatively favorable outcome in patients with T-ALL transplanted in CR1, and might be an option for subgroups of patients in more advanced phase of the disease. Of note, use of TBI as part of the conditioning regimen is associated with an improved LFS in all disease stages. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽

10.1182/blood.v122.21.5467.5467 ◽

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.

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