scholarly journals Nonmyeloablative Stem Cell Transplantation with CD8-Depleted or Unmanipulated Peripheral Blood Stem Cells: A Prospective Randomized Trial.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1075-1075
Author(s):  
Evelyne Willems ◽  
Emilie Castermans ◽  
Frédéric Baron ◽  
Etienne Baudoux ◽  
Nadine Wanten ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Chronic Gvhd ◽  
Survival Rates ◽  
Peripheral Blood Stem Cells ◽  
Cd8 Cells ◽  
Group 2 ◽  
Cd8 Depletion ◽  
Group 1

Abstract Background: In a previous pilot study, we demonstrated that CD8-depletion of the graft apparently reduced the severity of AGvHD without impairing the GvL effect after peripheral blood stem cell (PBSC) transplantation with a nonmyeloablative conditioning (NMSCT). Aim of the study: To evaluate the effect of CD8-depletion on graft rejection, AGvHD and CGvHD, and relapse. Patients: 53 patients were randomised between CD8-depletion (group 1) (n=25) and no manipulation (group 2) (n=28). Two patients in the CD8 group were excluded for poor CD34+ cell count collected. Diagnoses were: AML (n=3), CML-AP (n=2), MDS (n=14), MPD (n=3), CLL (n=5), NHL (n=14), MM (n=8) and RCC (n=2). Median age was 57 (range 36–69) yrs. After conditioning with 2 Gy TBI with (n=39) or without (n=12) fludarabine, patients received PBSC from family (n=21) or unrelated (n=30) HLA-matched donors. CD8-depletion was carried out using the Eligix system and GvHD prophylaxis consisted in CyA and MMF. Results: CD8 depletion removed 96% of CD8+ cells so that the number of CD8+ cells infused was 6.8 vs 136.8 x108 cells/Kg in group 2 (p<0.0001). AGvHD of any grade was observed in 13 (56%) patients in group 1 and 17 (61%) in group 2 (NS); it was grade 3–4 in 1 (4%) and 5 (18%) patients in groups 1 and 2, respectively (NS). Limited and extensive CGvHD developed in 3 and 1 patients in group 1 and in 7 and 2 patients in group 2, respectively (NS). Nine patients in group 1 and 12 in group 2 received unmanipulated DLI for poor chimerism or disease progression. Eight (3 initial and 5 late) graft failures were observed in group 1 and one (late) in group 2. Full donor chimerism was achieved in 57% (group 1) and 50% (group 2) at day 100, and in 73% (group 1) and 59% (group 2) (NS) at 1 yr. The 2-yr OS and PFS rates are 55% and 43 % in group 1 vs 59% and 46% in group 2, respectively (NS). Four (17%) patients died of their disease in group 1 vs 3 (11%) in group 2 (NS). Two patients died of severe AGvHD in group 2 vs none in group 1. Conclusion: In vitro CD8-depletion results in higher rates of graft failure after NMSCT. The incidence of acute and chronic GvHD is not reduced but there is a trend towards reduced severity of AGvHD. Relapse and survival rates are not changed by this strategy.

Optimization of Plerixafor Utilization Based on Peripheral Blood CD34+ Count for Autologous Peripheral Blood Stem-Cell Collection

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 41-41
Author(s):  
Gaurav K. Gupta ◽  
Sera Perreault ◽  
Stuart Seropian ◽  
Christopher A. Tormey ◽  
Jeanne E. Hendrickson
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Medical Center ◽  
Tertiary Care ◽  
Peripheral Blood Cd34 ◽  
Tertiary Care Medical Center ◽  
Group 2 ◽  
Group 1

Introduction: Peripheral CD34+ cells may be mobilized using filgrastim (G-CSF) alone or in combination with chemotherapy. However, some patients also require plerixafor, an inhibitor of C-X-C chemokine receptor type-4, for adequate mobilization. Given its cost, judicious utilization of plerixafor is warranted. Material and Methods: A retrospective analysis of autologous stem-cell mobilization was performed at a tertiary-care medical center in adult patients with multiple myeloma and lymphoma; here we will focus on the utility of repeat plerixafor dosing. Patients were mobilized at the treating physician's discretion with filgrastim plus plerixafor or chemotherapy plus filgrastim plus plerixafor. Collections were initiated once peripheral CD34+ counts reached 20/µL (or 10/µL if chemotherapy mobilized); plerixafor was administered if these counts were not reached after 4 or 8 days, respectively, of filgrastim treatment. Results: Patients with multiple myeloma (86) or lymphoma (30) were evaluated. One hundred five were mobilized by filgrastim plus plerixafor and 11 by chemotherapy plus filgrastim plus plerixafor. No patient that received plerixafor with a CD34+ count <5/µL after chemotherapy mobilized the next day. The end collection goal was achieved in 86 (81.9%) of the filgrastim plus plerixafor group and 7 (63.6%) of the chemotherapy plus filgrastim plus plerixafor group. Patients given at least one dose of plerixafor were divided into groups based on collection goal, peripheral blood CD34+ cell count after 1 dose and the first day collection yield: Group 1) Goal of 3x10^6/kg and CD34+ count ≥ 30 cell/µL vs < 30 cell/µL; Group 2) Goal of 6x10^6/kg and ≥ 50% of collection goal after 1 day of collection vs CD34+ count < 50 cell/µL or < 50% of collection goal. Forty of 42 (95%) patients in Group 1 with a CD34+ count ≥ 30 cell/µL achieved their end collection goal after one plerixafor dose. Eighteen of 19 (95%) patients in Group 1 with a CD34+ count <30 cell/µL received a second dose of plerixafor and 8 (44.4%) achieved their end collection goal. Twenty-eight of 32 (87.5%) patients in Group 2 with ≥ 50% of collection goal achieved on the first day of collection reached their end collection goal after one plerixafor dose. Nine of 12 (75%) patients in Group 2 with a CD34+ count of < 50 cells/µL or <50% collection goal received an additional dose of plerixafor and 6 (66.7%) achieved their end collection goal. Conclusion: Based on these data, we have developed the following repeat plerixafor dosing algorithm: 1) for a collection goal is 3x10^6/kg, administer a second dose of plerixafor if the CD34+ count on the first day of collection is < 30 cell/µL, and 2) for a collection goal of 6x10^6/kg, administer a second dose of plerixafor if the CD34+ count on the first day of collection is < 50 cell/µL or if the first day of collection yields <50% of the end goal. This algorithm optimizes pharmacy, apheresis and stem cell processing resources. Disclosures No relevant conflicts of interest to declare.

scholarly journals Post-Transplant Cyclophosphamide and Thymoglobulin, a Graft-Versus-Host Disease Prophylaxis in Matched Sibling Donor Peripheral Blood Stem Cell Transplantations

2020 ◽  
Vol 29 ◽  
pp. 096368972096590
Author(s):  
Chutima Kunacheewa ◽  
Weerapat Owattanapanish ◽  
Chutirat Jirabanditsakul ◽  
Surapol Issaragrisil
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Chronic Gvhd ◽  
Survival Rates ◽  
Free Survival ◽  
Graft Versus Host ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Matched Sibling

Post-transplant cyclophosphamide (PTCy) has been explored in several types of stem cell transplantations (SCTs) and it proved highly effective in controlling graft-versus-host disease (GvHD) without aggravating relapsed disease. However, PTCy alone has resulted in inferior outcomes in matched sibling donor (MSD) employing peripheral blood (PB) SCTs. We hypothesized that adding thymoglobulin to PTCy would be able to control GvHD effectively. We retrospectively compared the use of standard GvHD prophylaxis encompassing a combination of PTCy and thymoglobulin (ATG) in patients with myeloid malignancies in a myeloablative conditioning MSD PBSCT. Forty-two patients underwent PBSCT using either methotrexate and cyclosporine (MTX/CSA, 21 patients) or PTCy and ATG (21 patients) as a GvHD prophylaxis. With median follow-ups of 71 months, the 1-year GvHD-free, relapse-free survival rates and chronic GvHD-free survival rate of the standard and PTCy/ATG groups were similar: 24% versus 37% ( P = 0.251) and 29% versus 43% ( P = 0.095), respectively. When focusing on chronic GvHD we observed that 17/35 patients (48.6%) suffered from this, 5/18 (27.8%) treated with MTX/CSA had extensive chronic GvHD, but 0/17 PTCy/ATG did. Twenty-one patients required additional GvHD treatment; 7/21 in the PTCy/ATG received only corticosteroid, while 8/14 MTX/CSA required at least 2 drugs. The 5-year overall survival rates were 52% and 52% ( P = 0.859), and the 5-year disease-free survival rates were 52% and 52% ( P = 0.862) for the MTX/CSA and PTCy/ATG groups, respectively. We conclude that PTCy in combination with ATG without immunosuppression of a calcineurin inhibitor can effectively control GvHD.

CMV Immunity Status in Older (>50 Years Old) Subjects after Non-Myeloablative or Reduced Intensity Regimen for Hematopoietic Cell Transplantation (HCT): A Comparison with a Younger Cohort after Ablative HCT.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3246-3246
Author(s):  
Ghislaine Gallez-Hawkins ◽  
Lia Thao ◽  
Simon F. Lacey2 ◽  
Joybelle Martinez ◽  
Anne E. Franck ◽  
...  
Keyword(s):  
Immune Response ◽  
Stem Cell ◽  
T Cell ◽  
Cell Transplantation ◽  
Immune Reconstitution ◽  
Cmv Infection ◽  
Cd8 Cells ◽  
Group 2 ◽  
Reduced Intensity ◽  
Group 1

Abstract Immunity declines with age as demonstrated by cell-mediated and humoral responses to alloantigens. The susceptibility of these elderly subjects to endogenous virus infection, such as human cytomegalovirus (HCMV) reactivation, is a particular concern during the process of hematopoietic stem cell transplantation (HCT) and immune reconstitution. In this report, the host contribution to stem cell engraftment and differentiation was evaluated by comparing the HCMV immune response in older subjects (> 50 y.o.) to a younger (< 50 y.o.) transplant population. This was a retrospective analysis of a subset of data collected prospectively and with IRB approval for characterization of the CMV immune response of allogeneic transplant patients. Within the dataset, two groups of patients were compared. Group 1 consisted of 10 patients >50 y.o. who had received reduced intensity or non-myeloablative conditioning regimen, and Group 2 consisted of 13 patients <50 y.o., most of whom had received a myeloablative regimen. Because 9 of 10 in Group 1 had had CMV reactivation, Group 2 was selected from the subset of younger patients with known post-transplant CMV infection. CMV infection was defined as either a positive CMV blood culture using shell vial assay or a positive CMV PCR on plasma. Subjects were assessed on days 40, 90, 120, 150, 180, and 360 post-HCT by CMV-specific tetramer-binding assay using CD8 cells, assays for intracellular INF-g response of CD4 and CD8 cells, and a T-cell receptor excision circle (TREC) assay. There were no significant differences observed in the CD4+/IFN-g+ cell responses to CMV antigen nor were the rates of activated CD4+/CD69+/IFN-g+ cells different between the groups. Group 1 was also characterized by a robust CD8+/IFN-g+ response to HLA-specific CMV peptides, and all subjects had ≥ 2cells/μl by day 150 post-HCT. The frequency of CMV tetramer positive cells (≥ 2cells/μl) was 50% in Group 1 by day 90 post-HCT and was not statistically different from Group 2. The T cell renewal in the thymus as measured by the TREC spanned over 0 -- 92 copies/μg of total cellular DNA in Group 1 and from 0 – 129 copies/μg in Group 2 during the first year post-HCT (n.s.). In conclusion, CMV immune reconstitution in older transplant subjects, who undergo a reduced intensity or non-myeloablative regimen, is robust and, in this small sampling, did not differ from that observed in a younger adult group.

scholarly journals Complementary Transplantation Improved Results of Both Peripheral Blood Stem Cells and Unrelated Cord Blood Transplants in Thalassemia: A Multi-Center Study from China

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4617-4617
Author(s):  
Chunfu Li ◽  
Sixi Liu ◽  
Yuelin He ◽  
Xiaodong Wang ◽  
Jianyun Liao ◽  
...  
Keyword(s):  
Cord Blood ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Ct Protocol ◽  
Significant Difference ◽  
Group 2 ◽  
Unrelated Cord Blood ◽  
Group 1

Background: Unrelated cord blood (UCB) transplant (UCBT) is not recommended in patients with thalassemia major (TM) so far. Post-transplant (PT) Cyclophosphamide (PTCy) with long pre-transplant immunosuppression therapy have improved haploidentical peripheral blood (PB) stem cell transplant (haplo-SCT) survival in TM patients but with 2/31 primary rejection. So, we designed a novel dual transplantation of UCBT following haplo-SCTwith PTCy(NF-14-TM-CT protocol). Aim:To improve results of haplo-SCT and UCBT in patients with TM. Patients and method: NF-14-TM -CT protocol was termed as double-insurance dual transplantsincluding a haplo-SCT and an UCBT, in which conditioning regimen consisted of ATG (at -10 to -8 day), Cy (-7), Fludarabine (-6 to -2), Busulfan (-6 to -4) Thiotepa (-3), haplo-PB (0), PTCy (+3, +4) and UCB (+6). PTCy serve as GVHD prophylaxes after haplo-SCT and as conditioning before UCBT. In total 131 patients with TM from three pediatric center in China received NF-14-TM-CT protocolfrom June, 2014 to April, 2019, with a median follow-up of 13 (2-59) months and a median age of 8 (3.5-17) years. Results Final haplo-PB engrafted(group1)in 76 patients with mean PBSC-MNCof 22.49 (±5.36) x108/kgand UCB nuclear cells (NC) of 5.95 (±3.39) x107/kg and final UCB engrafted (group 2) in 55 patients with mean PBSC-MNC of 21.78 (±5.68) x108/kg and mean UCB-NC of. 5.43 (±2.32) x107/kg. The 4-year overall survival (OS), thalassemia-free survival (TFS), graft rejection (GR), and transplant related mortality (TRM) were 97.6%, 96.0%, 1.5%, and 2.4%, respectively (Fig. A), in total. The corresponding rates for group 1 were 98.3%, 96.9%, 1.7% and 1.8% and for group 2 were 95.5%, 93.8%, 4.5% and 1.4%, respectively. No statistic significant difference was found in OS, TFS, GR and TRM, respectively, when comparing group 1 with group 2 (Fig. B. C, D, E).The incidence of grade II-IV acute GVHD, III-IV acute GVHD, mild chronic GVHD, moderate/severe chronic GVHD, VOD, PT cystitisand PT hemolysis of the entire cohort was 16.8%, 6.87%, 9.92%, 1.52%, 4.60%, 31.3% and 14.5, respectively. Summary:Current study proved that the novel CT improved the results of haplo-SCT and UCBT in patients with TM. Disclosures Wing: Miltenyi Biotec: Employment.

Characterisation of Leukaemic Stem Cell Populations in Childhood AML Indicate Distinct Disease Subtypes with Diverse Clinical Features

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1500-1500
Author(s):  
Victoria J Weston ◽  
Tracey A Perry ◽  
Katie Brown ◽  
Shaun R Wilson ◽  
Pamela R Kearns
Keyword(s):  
Stem Cell ◽  
Cd38 Expression ◽  
Group 4 ◽  
Childhood Aml ◽  
Group 3 ◽  
The Mean ◽  
Group 2 ◽  
Stem Cell Populations ◽  
Group 1

Abstract Abstract 1500 Five year survival rates for childhood AML in children are currently 55–65%. AML is an extremely heterogeneous disease, and while prognostic significance of some karyotypic abnormalities has become evident, the biology of the disease remains largely unknown. Full characterisation of leukaemia initiating cells which may be responsible for relapse has not yet been undertaken. We investigated the leukaemic stem cell populations from 10 childhood primary AML samples by comparing expression of CD34, CD38 and CD45RA, a marker of a committed granulocyte-macrophage progenitor (GMP)-like population frequent in adult AML, in vitro daunorubicin sensitivity and engraftment in immuno-compromised NOD/Shi-scid/IL-2Rgnull (NOG) mice. Consequently, we were able to classify AML samples into 4 subgroups. These comprised Group 1, CD34+CD38- AML (n=1); Group 2, CD34-CD38+CD45RA- (<10% CD34+ blasts) AML (n=4); Group 3, CD34+CD38+CD45RA- (>10% CD34+ blasts) AML (n=4); and Group 4, CD34-CD38+CD45RA+ (<10% CD34+ and >10% CD45RA+ blasts) (n=1). There was no apparent enrichment for high risk prognostic karyotypes in any of the groups. The Group 1 AML presented at 3y with t(16;21); In Group 2 AMLs, the mean presentation age was 11y, 2 carried good prognostic t(8;21), while 1 had MLL involvement and 1 had FLT3-ITD with chromosome 13 isodisomy, both higher risk indicators; The Group 3 AMLs presented with a mean age of 11.9y and 2 carried good prognostic inv(16) whereas 2 had FLT3-ITD one with additional chromosome 13 isodisomy, t(5;11) and TP53 loss. Finally, the Group 4 AML presented at 1.5y with a normal karyotype. When we compared the 2 most frequent subgroups, Group 2 had a much shorter mean EFS of 122d (n=2) compared with a 275d (n=4) for Group 3 (the mean follow up was 282d and 1013.5d, respectively). We next sorted four cell subpopulations based on CD34 and CD38 expression (CD34+CD38-, CD34+CD38+, CD34-CD38- and CD34-CD38+ blasts) and compared in vitro sensitivity to daunorubicin. In Group 1, CD34- and CD34+ cells were equally sensitive at nanomolar IC50 doses. In 2 of the Group 2 AMLs,CD34-CD38- cells were the most resistant to daunorubicin at micromolar IC50 doses (2.5-10mM) whereas the CD34-CD38+ cells (also the dominant subpopulation in this group) were the most sensitive cells exhibiting nanomolar IC50 doses (750–800nM). In contrast, the Group 3 AMLs were overall more sensitive to daunorubicin exhibiting lower nanomolar IC50 doses. Again in this group, the CD34-CD38- cells were typically the most resistant (this time being the dominant subpopulation) whereas the CD34+CD38+ were the most sensitive cells. Finally, in the Group 4 AML, while CD45RA+ cells rapidly underwent spontaneous apoptosis, CD45RA- cells exhibited extreme resistance to daunorubicin (IC50 >10mM) and CD38 expression had no impact on sensitivity. The reduced sensitivity of Group 2 AMLs to daunorubicin compared with Group 3 could, therefore, be an underlying factor contributing to shorter EFS. Finally, we initiated comparison of the stem cell qualities of the different subpopulations from representative samples from each of the two major subgroups, first by assessment of differentiation potential in vitro, and second by engraftment in vivo using NOG mice. In on-going experiments, the time to leukaemia will be compared between mice injected with unsorted and sorted cells and, at terminal cull, cells harvested from organs will be characterised by karyotype and immunophenotype and tested for clonogenic potential via subsequent serial transplantations. Peripheral blood sampling currently suggests higher human CD45+ engraftment in mice injected with sorted versus unsorted cells, and these are CD34+CD33+CD3- recapitulating the AML phenotype. We anticipate that particular subpopulations will be enriched for AML stem cells with the ability to repopulate the leukaemia. Overall, we have shown that childhood AML is diverse with respect to stem cell characteristics. AMLs with low CD34 (Groups 2 and 4) exhibit the greatest overall resistance to daunorubicin as well as shorter EFS. Furthermore, in the majority of AMLs, CD34-CD38- blasts exhibit the least sensitivity to daunorubicin. Novel therapies which can target these resistant subpopulations with leukaemia initiating activity could significantly improve the treatment responses in this clinically challenging disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clonogenicity of circulating neuroblastoma cells: implications regarding peripheral blood stem cell transplantation

Blood ◽  
1994 ◽  
Vol 83 (10) ◽  
pp. 3085-3089 ◽  
Author(s):  
TJ Moss ◽  
M Cairo ◽  
VM Santana ◽  
J Weinthal ◽  
C Hurvitz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tumor Cell ◽  
Peripheral Blood ◽  
Clonogenic Assay ◽  
Neuroblastoma Cells ◽  
Tumor Stem Cell ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Blood Samples

Abstract Peripheral blood stem cells (PBSCs) are being used as an alternative to autologous marrow rescue for hematopoietic reconstitution after high- dose chemotherapy in patients with neuroblastoma and other solid malignancies. Use of PBSCs is preferred by some because of the belief that there is less risk of tumor contamination. Because tumor stem cell contamination is thought to be one contributing cause of relapse after myeloablative therapy and autologous reconstitution, we examined the potential risk of reinfusing circulating neuroblastoma cells by in vitro evaluation of their clonogenicity. Immunocytologic and tumor cell clonogenic analyses were performed on 74 blood samples obtained from 56 children with advanced-stage neuroblastoma. Concurrently drawn bone marrow specimens were evaluated in 30 instances. Circulating neoplastic cells were detected in 19 of 74 (26%) for all specimens and by immunologic techniques (26%). Using a clonogenic assay, 13 grew identifiable tumor colonies. Comparing results with the two techniques showed tumor colony growth in 10 of the 19 positive specimens by immunocytology. However, 3 of 53 samples (6%) that were negative by immunocytology were positive by the clonogenic assay. Of the 11 positive blood samples, 9 concurrent marrows contained neuroblastoma cells; of the 19 negative blood specimens, 3 concurrent marrows had metastatic disease. We conclude that circulating neuroblastoma cells are present in peripheral blood and have clonogenic properties in vitro. This supports the view that tumor cell contamination may well be one cause of relapse after autologous reconstitution. Consequently, PBSC collections should also undergo meticulous monitoring for tumor contamination before autologous reinfusion.

scholarly journals Extended follow-up of methotrexate-free immunosuppression using sirolimus and tacrolimus in related and unrelated donor peripheral blood stem cell transplantation

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 3108-3114 ◽  
Author(s):  
Corey Cutler ◽  
Shuli Li ◽  
Vincent T. Ho ◽  
John Koreth ◽  
Edwin Alyea ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Peripheral Blood ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Peripheral Blood Stem Cells ◽  
Gvhd Prophylaxis

Abstract We assessed the combination of sirolimus and tacrolimus without methotrexate after myeloablative allogeneic stem cell transplantation from 53 matched related donors (MRDs) and 30 unrelated donors (URDs). All patients received cyclophosphamide and total body irradiation conditioning followed by transplantation of mobilized peripheral blood stem cells. The median time to neutrophil engraftment was 14 days. The median time to platelet engraftment was 12 days. No differences between MRD and URD cohorts was noted. The incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) were 20.5% and 4.8%. The cumulative incidence of chronic GVHD was 59.1%. There were no differences in acute or chronic GVHD incidence between MRD and URD cohorts. The omission of methotrexate was associated with low transplant-related toxicity, with 30-day and 100-day treatment-related mortality rates of 0% and 4.8%. Relapse-free survival at 1 and 2 years was 72.3% and 68.5%, respectively. Overall survival at 1 and 2 years was 77.1% and 72.2%, respectively. There were no differences in relapse-free or overall survival between MRD and URD cohorts. The substitution of sirolimus for methotrexate as GVHD prophylaxis is associated with rapid engraftment, a low incidence of acute GVHD, minimal transplant-related toxicity, and excellent survival. Differences between MRD and URD cohorts are not evident when effective GVHD prophylaxis is used.

Reduced Risk of Residual Molecular and Hematological Relapse in Patients with Cml after KIRir-Ligand Mismatched Hematpoietic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 974-974
Author(s):  
Ahmet H. Elmaagacli ◽  
Hellmut Ottinger ◽  
Koldehoff Michael ◽  
Peceny Rudolf ◽  
Nina K. Steckel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Chronic Phase ◽  
Hla Class I ◽  
Hla Class I Antigen ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract We compared the incidence of molecular and hematological relapse in 236 CML patients (pts) after HLA-identical (n=158) [group 1], HLA class I antigen mismatched and KIR-ligand compatible (n=49) [group 2], and HLA class I antigen mismatched and KIR-ligand incompatible (n=29) [group 3] hematopoietic stem cell transplantation. In group 1 133/158 (84%) pts were in first chronic phase of CML, the corresponding figures were 33/49 (67%) pts in group 2, and 19/29 (64%) in group 3 (p<0.05). Accordingly, 25/158 (16%) pts in group 1, 16/49 (33%) pts in group 2, and 10/29 (34%) pts in group 3 were in advanced disease phases of CML (accelerated phase, 2nd chronic phase, or blastic phase). Stem cell grafts were from sibling donors in 97% of pts in group 1, 37% of pts in group 2, and in 59% of pts in group 3 (p<0.01 group 1 versus groups 2+3). Median age and gender constellations were not different between the three groups (age medians between 37–41 years, range 16–63). Acute GVHD grade 2–4 occurred in 62/158 (39%) pts in group 1, in 24/49 (49%) pts in group 2, and in 15/29 (52%) pts in group 3 (NS). Estimates of chronic GVHD did not differ significantly between the study groups with 94% + 2% in group 1, 95% + 4% in group 2, and 91% ± 6% in group 3. Molecular relapse as detected by real-time RT-PCR occurred in 1/29 (3%) pts of group 3 compared to 62/158 (39%) of pts in group 1, and in 11/49 (22%) pts in group 2 (p<0.001). A hematological relapse developed in 20/158 (13%) pts in group 1, in 2/49 (4%) pts in group 2 and in 0/29 (0%) pts in group 3 (p<0.05). Multivariate analysis on the risk molecular relapse included possible influencial covariates like disease stage, age (> 40 years or < 40 years), gender matching of donor and recipient, occurrence of acute and chronic GVHD, HLA matching between donor and recipient, donor source [sibling or unrelated], and graft type [bone marrow or PBSCs]. This analysis confirmed that KIR-mismatches are a strong independent predictor for the occurrence of bcr-abl transcripts after transplantation (p<0.02). The 8-year overall survival estimates were not different between the three groups (67% group 1, 52% group 2 66% group 3). In conclusion, KIR-ligand incompatibility is an important prognostic factor for the occurrence of molecular and hematological relapse after allogeneic transplantation for CML.

Results of Non Myeloablative Geno-Identical Transplants in Adults with AML: Influence of the Doses of Peripheral Stem Cells Infused (on Behalf of the Acute Leukemia Working Party of EBMT).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5409-5409
Author(s):  
Norbert C. Gorin ◽  
Myriam Labopin ◽  
Francesco Frassoni ◽  
Vanderson Rocha
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
De Novo ◽  
Advanced Disease ◽  
Chronic Gvhd ◽  
Working Party ◽  
Peripheral Blood Stem Cells ◽  
Peripheral Stem Cells ◽  
Higher Doses

Abstract In adult patients with acute myelocytic leukaemia receiving a conventional myeloablative allogeneic stem cell transplantation, several studies have shown that the higher the doses of hemopoietic stem cells infused, the better the outcome, with a lower transplant related mortality (TRM), a lower relapse incidence (RI) and a better leukaemia free survival (LFS). We wondered whether this observation was transposable in the context of non myeloablative transplants with peripheral blood stem cells where graft versus leukaemia (GVL) is the only anti tumor mechanism generated by the procedure in an effort to control the disease. In this particular situation, one might postulate that increasing the doses of peripheral blood T cells infused in an effort to increase GVL might increase GVHD and TRM. Further, one might speculate on the existence of an optimal range of stem cell and T cell doses to infuse. From January 1998 to December 2003, 253 patients with de novo AML, who received a non myelo ablative transplant with peripheral blood from a genoidentical donor, were reported to the ALWP registry with the dose of cells infused available. The sex ratio of the patients was 56% male /female. Patient age was 55 years (18–72). 141 patients were transplanted in first remission (CR1), 47 in second remission (CR2) and 65 patients had refractory disease or were transplanted in relapse. The pretransplant reduced intensity regimens were variable but 91% included fludarabin and Total body irradiation (TBI) was used in 23% of the patients at a dose<5 Gy. The median dose infused was 9.09 x 108 nucleated cells/kg (1.23–24). The follow up was 17 months (2–67). The LFS of the total population at 2 years was 41± 4%. For patients transplanted in CR1, CR2 and more advanced disease, the LFS were 49 ± 6%, 50± 8% and 23± 6% and the RI 37±4%, 34±7% and 69±6% respectively. Patients transplanted in CR had a significantly lower RI (p< 10−4, RR= 0.43 (0.29–0.65)) and better LFS (p< 10−5, RR=0.49 (0.35–0.7)) than those transplanted with advanced disease. Patients receiving doses of peripheral blood nucleated cells above the median had a trend towards a lower RI (42±5% versus 47±4%; p=0.06, RR=0.67 (0.45–1.02)) and a significantly higher LFS (46±5% versus 37±5%; p=0.04, RR= 0.68 (0.48–0.98)). Higher doses of nucleated cells were associated to a higher incidence of chronic GVHD (59 ± 5% versus 41 ± 5%, p=0.01, RR= 1.75 (1.12–2.73)). Interestingly, the use of TBI was associated to a higher RI (51± 8% versus 43±4%; p=0.02, RR=1.8 (1.1–2.9)). There was no relationship with the doses expressed in CD34+ cells infused. We conclude that in the context of non myeloablative transplants for adult AML, infusing higher doses of PB nucleated cells is beneficial to the patients.

Optimal Conditioning Regimen for Haplo-Identical Stem Cell Transplantation in Adult Patients with Acquired Severe Aplastic Anemia: Prospective De-Escalation Study of TBI and ATG Dose

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2196-2196
Author(s):  
Sung-Eun Lee ◽  
Sung Soo Park ◽  
Young-Woo Jeon ◽  
Jae-Ho Yoon ◽  
Byung-Sik Cho ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Adult Patients ◽  
Free Survival ◽  
Group 4 ◽  
Optimal Conditioning ◽  
Group 2 ◽  
Group 1

Abstract Background Recent advances in controlling graft failure and graft-versus-host disease (GVHD) due to barrier of HLA incompatibilities in haplo-identical stem cell transplantation from related mismatched donor (Haplo-SCT) extended its application to severe aplastic anemia (SAA). Therefore, studies for searching optimal conditioning regimen and strategy of graft manipulations for SAA patients who receive Haplo-SCT are needed. This prospective study was aimed to explore the optimal conditioning regimen to ensure engraftment with minimal toxicity in adult patients with SAA who received Haplo-SCT. Methods We have explored a safe and sufficient dose of ATG in combination with 800 cGy TBI and fludarabine (Flu, 30 mg/m2/day) for 5 days using step by step dose de-escalation based on the transplant-related mortality (TRM) and toxicity. The dose of ATG was de-escalated from 10 mg/kg (group 1), 7.5 mg/kg (group 2), to 5 mg/kg (group 3) and from October 2014, the TBI dose also reduced to 600 cGy with fixed dose of Flu and ATG (5mg/kg) (group 4). If any patient developed TRM with engraftment in each group, we moved to next group. For GVHD prophylaxis, a combination of tacrolimus and short-course methotrexate was used. G-CSF mobilized PBSCs were used as stem cell source without manipulation. Considering the importance of both survival and GVHD rate when testing conditioning regimen, GVHD-free survival, defined as grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, or death was addressed. Results Twenty-nine patients including 18 men and 11 women were enrolled. The median age was 31 (17-52) years. Median CD34+ cells transplanted were 5.84x106/kg (1.45-16.2). All patients achieved primary engraftment. Thirteen patients (7 of 10 in the group 1-3, 6 of 19 in the group 4) had CMV DNAemia requiring pre-emptive therapy including 3 patients with CMV disease (2 pneumonia, 1 colitis). Three patients (2 in the group 1, 1 in the group 2) developed EBV-associated PTLD, of whom two patients with monomorphic type received rituximab and chemotherapy. The incidence of acute GVHD (grade ≥2) and chronic GVHD (≥ moderate) were 24% and 17%, respectively. With a median follow-up of 41.4 (31.9-48.9) months in the group 1-3 and 10.1 (1.3-20.6) months in the group 4, probability of overall survival (94.1% in the group 4 vs. 70% in the group 1-3, P = 0.292) and GVHD-free survival (73.3% in the group 4 vs. 50% in the group 1-3, P = 0.161) were improved in the group 4. Conclusions This study explored the optimal conditioning with step by step de-escalation dose of ATG and TBI to reduce TRM with sustained graft function. TBI-600 cGy/Flu/low-dose ATG resulted in feasible outcomes of Haplo-SCT for adult patients with SAA. Disclosures No relevant conflicts of interest to declare.

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