scholarly journals T-Cell Depletion Improves the Composite End Point Graft-Versus-Host Disease-Free, Relapse-Free Survival after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3204-3204
Author(s):  
Federico Simonetta ◽  
Stavroula Masouridi-Levrat ◽  
Yan Beauverd ◽  
Olga Tsopra ◽  
Yordanka Tirefort ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Cumulative Incidence ◽  
Disease Risk ◽  
Risk Index ◽  
Cell Depletion ◽  
Clinical Factors ◽  
T Cell Depletion ◽  
Free Survival ◽  
Allogeneic Hsct

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established therapeutic modality for a variety of hematological malignancies. Unfortunately it is associated with significant morbidity and mortality related to cancer relapse and transplant complications, including graft versus host disease (GvHD). GvHD-free, relapse-free survival (GRFS) is a recently reported composite end point which allows estimating risk of death, relapse and GvHD simultaneously [Holtan et al., Blood 2015 ]. T-cell depletion (TCD) is a well established strategy for GvHD prevention, but is probably associated with increased risk of relapse. In the present work we investigated the effect of partial TCD (pTCD) on GRFS in order to evaluate its impact on patientsÕ morbidity-free survival. Patients and methods: We performed a retrospective study on 333 patients who underwent allogeneic HSCT for hematologic malignancies at our center from 2004 to 2014 with grafts from HLA identical siblings or HLA 10/10 matched unrelated donors. 171 patients received pTCD grafts, obtained through incubation with alemtuzumab in vitro washed before infusion followed on day +1 by an add-back of donor T cells. 162 patients received T cell repleted (non-TCD) grafts. Donor lymphocyte infusions were given at three months to all patients without GvHD who had received pTCD grafts with reduced intensity conditioning and when needed to patients, transplanted with either pTCD or non-TCD grafts with mixed chimerism. Kaplan-Meier estimates were employed to determine the probability of 1-year and 5-year overall survival (OS), progression free survival (PFS) and GRFS. Events determining GRFS included grade 3-4 acute GvHD, systemic therapy-requiring chronic GvHD, relapse, or death. Differences between survival curves were determined using Log-rank Mantel-Cox test. Cox regression was used to examine the independent effect on OS, PFS and GRFS of clinical factors including age, underling disease, disease status at transplant, disease risk index, conditioning, donor type, stem cell source, year of transplantation and T-cell depletion. Cumulative incidence estimates of relapse and non-relapse mortality (NRM) were calculated with relapse or death from other causes defined as competitive events with the Fine and Gray method. Results: According to institutional practices, the group receiving pTCD grafts comprised more patients transplanted in complete remission (67%) than the group receiving non-TCD grafts (41%, p <0.0001). Similarly, the pTCD group comprised fewer patients with a high/very high disease risk index (17%) than the non-TCD group (51%, p <0.0001). pTCD was associated with improved 1-year and 5-year OS and PFS in univariate analysis, but this association failed to reach significance in multivariate analysis taking into account clinical factors differing among patients groups. pTCD was associated with significantly improved GRFS (1y 53.2%, 95%CI 45.4%-60.4%; 5y 40.3%, 95%CI 32.5%-47.9%) compared to non-TCD transplantations (1y 36.6%, 95%CI 29.1%-44.0%, p<0.0001; 5y 24.1%, 95%CI 17.1%-31.9%, p<0.0001) [Figure 1]. The effect of pTCD on GRFS remained highly significant in multivariate analysis performed taking into account clinical factors including disease status at transplant and disease risk index (1y HR 0.624, 95%CI 0.440-0.884, p=0.0079; 5y HR 0.625, 95%CI 0.454-0.861, p=0.0040). No effect of pTCD was observed on relapse cumulative incidence (1y pTCD 37.4%, 95%CI 29.9%-45%, non-TCD 33.3%, 95%CI 26.3%-40.5%, p=0.317; 5y pTCD 49.4%, 95%CI 40.4%-57-9%, non-TCD 47.2% 95%CI 39%-54.9%, p=0.396), although this result may be the consequence of aforementioned differences in patient groups studied. Conversely, 1-year and 5-year NRM cumulative incidence was significantly decreased in patients receiving pTCD (1y 4.8% 95%CI 2.2%-8.7%; 5y 9.7%, 95%CI 5.6%-15%) compared to patients receiving non-TCD allogeneic HSCT (1y 12.5%, 95%CI 7.9%-18.2%, p=0.0098; 5y 15.9% 95%CI 10.5%-22.2%, p=0.0449). Conclusion: pTCD appears to improve GRFS in allogeneic HCST recipients without significantly affecting OS and PFS. These results extend our knowledge about the effects of TCD on transplant-related morbidity and mortality, suggesting that pTCD could improve patientsÕ quality of life by reducing acute GvHD and NRM without impairing the curative potential of allogeneic HSCT. Figure 1. Impact of pTCD on GRFS. Figure 1. Impact of pTCD on GRFS. Disclosures Chalandon: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Decreased Incidence of GvHD after Reduced Intensity Conditioning and a Fixed T-CELL Dose in Hematological Malingnancy Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5889-5889 ◽  
Author(s):  
Audrey Simon ◽  
Eddy Roosnek ◽  
Yordanka Tirefort ◽  
Yan Beauverd ◽  
Carole Dantin ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Disease Risk ◽  
Risk Index ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
T Cell Depletion ◽  
Two Factors

Abstract Introduction: To decrease graft versus host disease (GvHD), the Geneva transplantation team has performed allogeneic hematopoietic stem cell (alloHSCT) with reduced intensity conditioning (RIC) and T cell depletion (TCD) to treat hematological malignancies for older or non fit for myeloablative conditioning patients. This is a new approach of engineering stem cell products that lowers the risk of GvHD while preserving graft versus leukemia (GvL) as much as possible. Patient and methods: We report a retrospective study of 73 patients who received alloHSCT with RIC and TCD between 2001-2013. The median age was 59 years (21-70), 60% were male. Disease at transplant time was acute leukaemia for 45%, Hodgkin lymphoma and non-Hodgkin lymphoma for 24%, myelodysplastic disorders for 13%, myeloproliferative disorders for 9,3 % and multiple myeloma for 8%. Source of stem cell was peripheral in 96% of the cases. 41% of the donors were matched related donor, 37% matched unrelated donor, 19% mismatched unrelated donor and 3% mistmatched related donor. The conditioning regimen consisted on fludarabine with busulfan or melphalan and ATG. Extensive T-cell depletion was done using Campath in the bag followed by washing procedures to remove free antibody. Fixed number of CD3+ T-cell addback was given on d+1 to preserve GvL with minimal residual disease (MRD) assessment and early donor lymphocyte infusions (DLI) given if MRD positive. Doses of DLI were preserved and frozen at the time of stem cell harvest. GvHD prophylaxis was with ciclosporine and mycophenolate mofetil. Results: With a median follow up of 5 (0.5-11) years, the 5-year overall survival (OS), disease free survival (DFS), current disease free survival, relapse rate and non relapse mortality (NRM) were 41.7% (95%CI 30.7-53.7%), 38.8% (95%CI 28.8-50.8%), 39,5% (95%CI 27.7-51.7%), 45.3% (95%CI 32.7-57.2%) and 15.8% (95%CI 8.3-25.4%) respectively. The main cause of death was relapse 38.7 % followed by GvHD 17% and infection 1.3%. In this cohort, the cumulative incidence (CI) of acute GvHD was 15.1% (95% CI: 8.0-24.3%) as well as for acute GvHD grade II-IV. CI of chronic GvHD was 14.7% (95%CI:7.2-23.6%) with extensive chronic GvHD CI being 5.9% (95% CI: 1.9-13.4%). Five patients received DLI for relapses, 27 for mixed chimerism and 8 for both causes. The average number of DLI was 2. Twenty-eight patients entered CR, 4 PR and 13 did not respond to DLI. In univariate analysis, two factors GvHD before DLI and GvHD after first DLI have a tendency for favorable impact on OS respectively p=0.093 and 0.071. For DFS, two factors are significant: disease risk index and GvHD after first DLI respectively p=0.013 and 0.044. For NRM disease risk index is the only factor which is statistically significant p=0.005. For relapse no factors were significant. Discussion: Our study showed a lower rate of acute and chronic GvHD as compared to other studies with unmanipulated stem cells. However, we describe a high rate of relapse incidence and relapse mortality. We have found in univariate analysis two factors statistically significant for DFS GvHD before and after first DLI. Our cohort is a heterogeneous group with different diseases at different stages, which can explain those results. It’s a monocentric study and small number of patient can be a limit for this work. Of note, since 2009 we have changed our strategy introducing a day +100 preemptive DLI infusion in the absence of GvHD, with escalading doses of lymphocytes every 8 weeks up to 5x 107 CD3/kg in the absence of GvHD to improve response. We don’t have enough patients and follow up to draw any conclusion regarding this new strategy. To improve the outcomes, the selection of patients who may receive partial T-cell depletion should be refined, avoiding transplanting patients with high risk of relapse with this strategy. To help decision making, the revised disease risk index as presented by Armand et al. (Blood 2014;123:3664) may be useful. Disclosures No relevant conflicts of interest to declare.

scholarly journals Effect of nonpermissive HLA-DPB1 mismatches after unrelated allogeneic transplantation with in vivo T-cell depletion

Blood ◽  
2018 ◽  
Vol 131 (11) ◽  
pp. 1248-1257 ◽  
Author(s):  
Betül Oran ◽  
Rima M. Saliba ◽  
Yudith Carmazzi ◽  
Marcos de Lima ◽  
Gabriela Rondon ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Risk ◽  
Risk Index ◽  
Allogeneic Transplantation ◽  
Cell Depletion ◽  
Matched Pairs ◽  
T Cell Depletion ◽  
Increased Risk ◽  
Key Points

Key Points After HSCT with in vivo T-cell depletion using ATG, HLA-DPB1 nonpermissive mismatches at the GVH direction increase the risk for aGVHD. HLA-DPB1–matched pairs have an increased risk for disease progression if intermediate risk by the Disease Risk Index.

scholarly journals Evidence of Effect Modification of Graft-Versus-Leukemia Effect of Cytomegalovirus By Alemtuzumab in Myeloid Malignancies Undergoing Unrelated Donor Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5927-5927
Author(s):  
Mohamed Shanavas ◽  
Jieun Uhm ◽  
Naheed Alam ◽  
Eshetu G Atenafu ◽  
John Kuruvilla ◽  
...  
Keyword(s):  
T Cell ◽  
Cumulative Incidence ◽  
Low Dose ◽  
Effect Modification ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
Relapse Free Survival ◽  
T Cell Depletion ◽  
Free Survival ◽  
Myeloid Malignancies

Abstract Several studies have suggested a beneficial effect of CMV seropositivity and or reactivation on relapse risk after allogeneic hematopoietic cell transplantation (HCT) in myeloid malignancies. Inability to replicate this finding in T cell depleted HCT is suggestive of a potential effect modification between TCD and CMV in this setting, but this has not been addressed in previously published studies. We have retrospectively analyzed transplant outcomes in 192 patients with myeloid malignancies who have undergone unrelated donor HCT at our center during January 2006 –November 2013. Among this 111 patients received in vivo TCD with low dose (30 mg) alemtuzumab and 81 patients received non-TCD transplants. Recipients were CMV seropositive in 57% of TCD transplants and 59% of non-TCD transplants. Analysis showed a significant effect modification (p=0.03 for interaction) between alemtuzumab and CMV serostatus on relapse risk, and stratified analysis based on recipient CMV status showed inferior outcomes with alemtuzumab in CMV seropositive recipients but not in CMV seronegative recipients. In CMV seropositive recipients alemtuzumab was an independent predictor of higher relapse (Hazard Ratio=13.95, p=0.008), inferior relapse free survival (HR=2.30, p=0.002), and inferior overall survival (HR= 2.04, p=0.008). There was no difference in NRM between CMV seropositive and CMV seronegative groups, or between TCD and non-TCD transplants. These findings suggest the presence of an effect modification by TCD on CMV's effect on relapse, resulting in inferior transplant outcomes with low dose Alemtuzumab in CMV seropositive recipients, but not in seronegative recipients. Figure 1. CIR, NRM, RFS, and OS showing differential effects of T cell depletion between CMV seropositive and seronegative recipients (A-B) Cumulative incidence of relapse, (C-D) Non-relapse mortality, (E-F) Relapse free survival, and (G-H) Over all survival. Figure 1. CIR, NRM, RFS, and OS showing differential effects of T cell depletion between CMV seropositive and seronegative recipients. / (A-B) Cumulative incidence of relapse, (C-D) Non-relapse mortality, (E-F) Relapse free survival, and (G-H) Over all survival. Disclosures Off Label Use: Alemtuzumab for GVHD prophylaxis.

scholarly journals Impact of Different In Vivo T Cell Depletion Strategies on Outcomes Following Hematopoietic Stem Cell Transplantation for Idiopathic Aplastic Anaemia: A Study on Behalf of the EBMT SAA Working Party

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1210-1210 ◽  
Author(s):  
Sujith Samarasinghe ◽  
Simona Iacobelli ◽  
Cora Knol ◽  
Rose-Marie Hamladji ◽  
Gerard Socie ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Cell Depletion ◽  
Event Free Survival ◽  
T Cell Depletion ◽  
Educational Support ◽  
Free Survival

Abstract To determine the optimal serotherapy regimen in idiopathic aplastic anaemia stem cell transplantation, we analysed 1837 patients who underwent either in vivo T cell depletion with either ATG (n=1283) or Alemtuzumab (n=261) or no serotherapy (n=293) as part of their conditioning regimen. All patients had either undergone a matched sibling or matched unrelated donor stem cell transplant (at least 6 out of 6). Data was obtained retrospectively from the EBMT SAA database, between the periods 2000-2013. The major endpoints were graft versus host disease, overall survival and event free survival. Events were classified as graft failure, secondary malignancy, relapse and requirement for second transplant. The median follow up was 34 months in the ATG group, 30.9 months in the Alemtuzumab group and 47.9 months in the no serotherapy group. Rate of grade 2-4 acute GVHD was 19.1% without serotherapy; this was higher than that observed with both ATG (13.3%, p<0.001) and Alemtuzumab (6.7%, p<0.001; ATG vs Alemtuzumab: p=0.012). Cumulative incidence of chronic GVHD at 36 months was 30.4% without serotherapy; this was higher than that observed with both ATG (20.8%, p=0.021) and Alemtuzumab (14.7%, p=0.003; ATG vs Alemtuzumab: p=0.083). In multivariate analysis, grade 2-4 acute and chronic GVHD rates were significantly lower with Alemtuzumab compared to no serotherapy (Odds Ratio ratio (OR) = 0.16, p< 0.001 95%CI 0.08-0.31 and HR= 0.38, 95% CI 0.24-0.62, p< 0.001 respectively). Similarly, acute and chronic GVHD were lower with Alemtuzumab compared to ATG (OR = 0.26;p<0.001 95%CI 0.14-0.47 and HR = 0.58; 95%CI 0.38-0.89, p=0.012 , respectively). Acute and chronic GVHD were higher without serotherapy compared to ATG (OR = 1.65; p =0.01 95%CI 1.12-2.41 and HR = 1.51; 95%CI 1.12-2.04, p=0.008 , respectively). There was no difference in event free survival between the three groups. However, overall survival at 36 months was 73.3%, 81.3% and 81.5 in no serotherapy, ATG and alemtuzumab, respectively (ATG vs no serotherapy p=0.01; Alemtuzumab vs no serotherapy p=0.025; Alentuzumab vs ATG p=0.604). In multivariate analysis overall survival favoured in vivo T cell depletion compared to no serotherapy; (Alemtuzumab vs no serotherapy, HR=0.44; 95%CI 0.29-0.67, p<0.001); (no serotherapy vs. ATG HR=1.55; 95%CI 1.19-2.01, p=0.001). Among serotherapy, Alemtuzumab was associated with better OS as compared with ATG (OR=0.68; 95%CI 0.48-0.98, p=0.037). Our results suggest that use of in vivo T cell depletion in sibling and unrelated matched stem cell transplantation in idiopathic aplastic anaemia leads to a survival advantage. Alemtuzumab is associated with less GVHD than ATG without affecting event free survival. Figure 1. Figure 1. Disclosures Snowden: Celgene: Other: Educational support, Speakers Bureau; Janssen: Other: Educational support, Speakers Bureau; MSD: Consultancy, Other: Educational support, Speakers Bureau; Sanofi: Consultancy. Dufour:Pfizer: Consultancy. Risitano:Pfizer: Consultancy; Novartis: Research Funding; Rapharma: Consultancy, Research Funding; Alnylam: Consultancy, Research Funding; Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: this paper includes discussion of the use of alentuzumab for GVHD prophylaxis, which is currently off-label.

scholarly journals T Cell Depleted Allogeneic Stem Cell Transplants for Hematological Malignancies: A 20 Year Experience Shows No Relationship Between Choice of Transplanted T Cell Dose or Delayed T Cell Add-Back on Major Outcomes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2013-2013
Author(s):  
Prathima Anandi ◽  
Xin Tian ◽  
Puja D. Chokshi ◽  
Noelle Watters ◽  
Sawa Ito ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Cell Depletion ◽  
Cell Transplant ◽  
T Cell Depletion ◽  
Cell Dose ◽  
Increased Risk

Abstract Introduction: T cell depletion of the stem cell allotransplant (SCT) has the advantage of reducing incidence and severity of GVHD but can be complicated by relapse and infection. An optimum residual T cell dose in T depleted SCT is not known. To optimize T cell depletion we delivered a series of fixed T cell transplant doses with scheduled T cell add back post-SCT in a series of protocols to determine the T cell doses that secured immune reconstitution, and minimized relapse and infection. Here we retrospectively examined large series of patients (pts) transplanted in a single institution where T cell dose at SCT and add back were quantitated. Unique to these protocols was the precise measurement of CD3 dose/kg at transplant for every patient which enabled us to relate transplant T cell doses to outcome. Patients and methods: 205 pts (106 males, 99 females) underwent HLA identical sibling allogeneic T cell depleted SCT between 1994 and 2014. Diagnosis at SCT included AML (48%), MDS (17%), ALL (27%), CLL (5%), MM (3%). Disease risk at SCT was classified as high (57%) or standard (43%). The median age at SCT was 37 (range: 10-75) yrs. TBI based myeloablative conditioning was used. The graft source was marrow in 20 pts and peripheral blood in 195 pts. GVHD prophylaxis was low dose cyclosporine. Different T cell depleted methods were used consecutively: elutriation, Isolex ®, Cellpro ® CD34, and Miltenyl © CD34 selection. A defined T cell dose was allocated at SCT by protocol ranging from 2 - 50 × 104 CD3+ cells/kg. Various schedules were used to add back T lymphocytes between day 30 to 90 with doses ranging 5 - 60 ×106 CD3+ cells/kg by protocol and no T cell add-back was given in 28 pts in recent protocols. Overall survival (OS) was estimated by the Kaplan-Meier method, and cumulative incidence of relapse and nonrelapse mortality (NRM) was estimated by Gray's method to account for competing risks. Cox proportional hazard regression models were used to assess the association of factors at baseline, day 100 and GVHD with the post-SCT outcomes. Results: At a median follow-up of 8.6 yrs (range: 0.7- 19.8) for surviving pts, 112 pts died (52 from NRM) and 68 pts relapsed. OS was 47%, 43% and 41%, NRM was 24%, 27% and 27%, relapse was 32%, 34% and 38% at 5 yr, 10 yr and 15 yr post SCT, respectively. Grade II-IV and III-IV acute GVHD were 41% and 13%, and chronic GVHD was 42% (25% limited, 17% extensive). In the multivariate models of baseline risk factors that adjusted for age at SCT and disease risk, T-cell doses at SCT did not affect OS, NRM or relapse. A higher dose of CD34+ cells at SCT was significantly associated with better OS and lower NRM. Disease risk was an independent predictor, with high-risk pts having more relapse and worse OS, compared to pts with standard risk. A landmark analysis of 156 pts surviving and relapse-free beyond day 100 was carried out to examine the effects of add back T cell schedules by day 100 and aGVHD. The total T-cell dose at add back by day 100 and different add-back T-cell schedules from day 30-90 had no impact on any outcome, controlling for T-cell dose at SCT. In the models controlling for age, risk, CD34+ and T-cell dose at SCT, pts with grade III-IV aGVHD by day 100 had an increased risk for overall mortality and NRM beyond day 100 (HR= 3 and 3.6, both P<0.001), but did not affect relapse. An analysis of pts surviving and relapse-free beyond 1 yr showed pts with extensive cGVHD had higher NRM rate (39%) and lower relapse rate (0%) after 1 yr post-HSCT compared to pts with no cGVHD ( NRM, 9%, P = 0.020; relapse 24%, P=0.026). Conclusion: These findings indicate that for myeloablative matched sibling SCT there is no ideal prescription of T cell dose at transplant within a range of 104 - 105 or for scheduled add back of lymphocytes within a range of T depletion 5 - 60 × 106. Instead, factors other than T cell dose either at transplant or when add-back was delayed determined GVHD incidence, relapse, and survival. These findings set a limit on the efficacy of any T cell depletion procedure to optimize transplant outcome. Disclosures No relevant conflicts of interest to declare.

scholarly journals Association between preconditioning absolute lymphocyte count and transplant outcomes in patients undergoing matched unrelated donor allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and anti-thymocyte globulin

2021 ◽  
Vol 12 ◽  
pp. 204062072110637
Author(s):  
Jeongmin Seo ◽  
Dong-Yeop Shin ◽  
Youngil Koh ◽  
Inho Kim ◽  
Sung-Soo Yoon ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Matched Unrelated Donor ◽  
T Cell Depletion ◽  
Reduced Intensity

Background: Allogeneic stem cell transplantation (alloSCT) offers cure chance for various hematologic malignancies, but graft- versus-host disease (GVHD) remains a major impediment. Anti-thymocyte globulin (ATG) is used for prophylactic T-cell depletion and GVHD prevention, but there are no clear guidelines for the optimal dosing of ATG. It is suspected that for patients with low absolute lymphocyte counts (ALCs), current weight-based dosing of ATG can be excessive, which can result in profound T-cell depletion and poor transplant outcome. Methods: The objective of the study is to evaluate the association of low preconditioning ALC with outcomes in patients undergoing matched unrelated donor (MUD) alloSCT with reduced-intensity conditioning (RIC) and ATG. We conducted a single-center retrospective longitudinal cohort study of acute leukemia and myelodysplastic syndrome patients over 18 years old undergoing alloSCT. In total, 64 patients were included and dichotomized into lower ALC and higher ALC groups with the cutoff of 500/μl on D-7. Results: Patients with preconditioning ALC <500/μl were associated with shorter overall survival (OS) and higher infectious mortality. The incidence of acute GVHD and moderate-severe chronic GVHD as well as relapse rates did not differ according to preconditioning ALC. In multivariate analyses, low preconditioning ALC was recognized as an independent adverse prognostic factor for OS. Conclusion: Patients with lower ALC are exposed to excessive dose of ATG, leading to profound T-cell depletion that results in higher infectious mortality and shorter OS. Our results call for the implementation of more creative dosing regimens for patients with low preconditioning ALC.

scholarly journals T-cell depletion of HLA-identical transplants in leukemia

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 2120-2130 ◽  
Author(s):  
AM Marmont ◽  
MM Horowitz ◽  
RP Gale ◽  
K Sobocinski ◽  
RC Ash ◽  
...  
Keyword(s):  
T Cell ◽  
Treatment Failure ◽  
Chronic Gvhd ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Cell Depletion ◽  
T Cell Depletion ◽  
Free Survival ◽  
Dose Rates ◽  
Leukemia Relapse

We analyzed the effects of T-cell depletion on the outcome of HLA- identical sibling bone marrow transplants for leukemia by comparing 731 T-cell-depleted transplants with 2,480 non-T-cell-depleted transplants. T-cell depletion decreased acute graft-versus-host disease (GVHD) (relative risk [RR] 0.45; P less than .0001) and chronic (GVHD) (RR 0.56; P less than .0001). However, it increased graft failure (RR 9.29; P less than .0001). Leukemia relapse also was increased. In first remission acute leukemia or chronic phase chronic myelogenous leukemia, leukemia relapse was 2.75 times more likely after T-cell-depleted transplants (P less than .0001). T-cell depletion increased the risk of treatment failure (RR 1.35; P less than .0003) and decreased leukemia- free survival. We also studied controllable variables associated with outcome of T-cell-depleted transplants. The unique findings were that among recipients of T-cell-depleted transplants for early leukemia, radiation doses greater than or equal to 11 Gy (RR 0.54; P less than .01), dose rates greater than 14 cGy/min (RR 0.56; P less than .002), and additional posttransplant immune suppression with cyclosporine alone (RR 0.53; P less than .0006) or cyclosporine plus methotrexate (RR 0.36; P less than .01) were associated with fewer treatment failures. Use of monoclonal antibodies rather than physical techniques for T-cell depletion (RR 2.01; P less than .03) and fractionated radiation (RR 1.69; P less than .05) were associated with increased treatment failure and lower leukemia-free survival. These data may be useful in designing strategies to improve results of T-cell-depleted transplants.

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