The abnormal distribution of NK cell subsets before HAART treatment may be related to the level of immune reconstitution in HIV patient

2021 ◽  
Vol 96 ◽  
pp. 107784
Author(s):  
Suyu Sun ◽  
Wanzhong Kong ◽  
Xiaoya Cui ◽  
Yin Lin ◽  
Bibi Lu ◽  
...  
Keyword(s):  
Immune Reconstitution ◽  
Nk Cell ◽  
Abnormal Distribution

scholarly journals Mouse Ly49G2+ NK cells dominate early responses during both immune reconstitution and activation independently of MHC

Blood ◽  
2011 ◽  
Vol 117 (26) ◽  
pp. 7032-7041 ◽  
Author(s):  
Isabel Barao ◽  
Maite Alvarez ◽  
Erik Ames ◽  
Mark T. Orr ◽  
Heather E. Stefanski ◽  
...  
Keyword(s):  
Nk Cells ◽  
Mhc Class I ◽  
Cytomegalovirus Infection ◽  
Immune Reconstitution ◽  
Nk Cell ◽  
Rapid Expansion ◽  
Normal Pattern ◽  
Mouse Cytomegalovirus ◽  
Single Positive ◽  
Independent Expansion

Abstract Natural killer (NK) cell subsets can be defined by the differential expression of inhibitory receptors for MHC class I molecules. Early after congenic HSCT, we found that Ly49G2high single-positive NK cells repopulated, displayed an activated phenotype, and were highly cytolytic. Over time, this subset was replaced with NK cells with a normal pattern of Ly49 expression. Treatment of mice with IL-2 also resulted in the rapid expansion of these Ly49G2high single-positive NK cells. Only the Ly49g (Klra7) Pro1 transcript was highly induced in both HSCT- and IL-2–treated recipients. MHC-independent expansion of the Ly49G2+ subset was also observed after Listeria monocytogenes or mouse cytomegalovirus infection. Our data indicate that during reconstitution after HSCT and various activation stimuli, Ly49G2+ NK cells represent the “first-responder” NK cells, which occur independently of NK-cell licensing via Ly49-MHC interactions. These data suggest that the inhibitory Ly49G2 receptor represents an activation marker on mouse NK cells under various conditions.

scholarly journals Changes in the NK Cell Repertoire Related to Initiation of TB Treatment and Onset of Immune Reconstitution Inflammatory Syndrome in TB/HIV Co-infected Patients in Rio de Janeiro, Brazil—ANRS 12274

2019 ◽  
Vol 10 ◽  
Author(s):  
Carmem Beatriz Wagner Giacoia-Gripp ◽  
Andressa da Silva Cazote ◽  
Tatiana Pereira da Silva ◽  
Flávia Marinho Sant'Anna ◽  
Carolina Arana Stanis Schmaltz ◽  
...  
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Rio De Janeiro ◽  
Immune Reconstitution ◽  
Nk Cell ◽  
Cell Repertoire ◽  
Tb Treatment ◽  
Inflammatory Syndrome

Immune Reconstitution after Haploidentical Hematopoietic Cell Transplantation: Impact of Reduced Intensity Conditioning and CD3/CD19-Depleted Grafts

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1175-1175
Author(s):  
Birgit Federmann ◽  
Matthias Haegele ◽  
Christoph Faul ◽  
Wichard Vogel ◽  
Lothar Kanz ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Cell Transplantation ◽  
Immune Reconstitution ◽  
Hematopoietic Cell Transplantation ◽  
Nk Cell ◽  
Reduced Intensity Conditioning ◽  
Haploidentical Hematopoietic Cell Transplantation ◽  
Reduced Intensity

Abstract Haploidentical hematopoietic cell transplantation (HHCT) using CD3/CD19 depleted grafts may lead to faster engraftment and immune reconstitution since grafts contain also graft-facilitating-cells, CD34− progenitors, NK cells, and dendritic cells. Reduced intensity conditioning may also have a positive impact on immune reconstitution following HHCT. 26 adults received CD3/CD19 depleted HHCT after RIC (150–200 mg/m2 fludarabine, 10mg/kg thiothepa, 120 mg/m2 melphalan and 5mg/day OKT-3 (day −5 to +14)) at our institution between 2005–2008. We prospectively evaluated engraftment and immune reconstitution. B-, NK-, T- and T-cell subsets (CD3/8, CD4/8, CD4/45RA/RO), TCR-Vβ repertoire and NK-cell receptors (NKP30, NKP44, NKP46, NKG2D, CD158a/b/e, CD85j, NKG2A, CD161) were analyzed by FACS. Grafts contained 8.8×106 CD34+ (range, 4.3–18.0 ×106), 2.9×104 CD3+ (range, 1.2–9.2×104) and 3.6×107 CD56+ (range, 0.02–23.0 ×107) cells/kg. Engraftment was rapid with a median time to >500 granulocytes/μl of 11 days (range, 9–15) and a median time to >20 000 platelets/μl of 11 days (range, 8–23). Full chimerism was reached on day 14 (median; range, 6–26). NK-cell engraftment was rapid, reaching normal values on day 20 (median of 247 CD16+CD56+CD3− cells/μl (range, 1–886)) with NK cells comprising up to 70% of lymphocytes. B-cell reconstitution was delayed with 81 (range, 0–280) and 335 (range, 11–452) CD19+20+ cells/μl on days 150 and 400, respectively. T-cell reconstitution was impaired with 49 (range, 0–586) and 364 (range, 35–536) CD3+ cells/μl on day 60 and day 150, respectively. We observed an increase of CD3+CD8+ cells in contrast to CD3+CD4+ cells early after HHCT with a median of 24 (range, 0–399) vs 16 (range, 0–257) and 159 (range, 1–402) vs 96 (range, 18–289) cells/μl on day 50 and day 200, respectively. CD4+CD45RA+ T cells increased slowly while CD4+CD45RO+ T cells reconstituted faster with a median of 61 CD4+CD45RO+ cells/μl (range, 0–310) vs 24 CD4+CD45RA+ (range, 0 to 152) on day 100. Within the CD4+CD25+ regulatory T cells there was a slow regeneration with median of 14 CD4+CD25+ cells/μl (range, 0–96) on day 100 and 28 CD4+CD25+ cells/μl (range, 19–160) on day 200. CD14+CD45+ monocytes did not reach normal values within the time of observation with 7 CD14+CD45+ cells/μl (range, 0–21) on day 120 and 7 CD14+CD45+ cells (range, 2–381) on day 400. TCR-Vβ repertoire and NK-cell receptor reconstitution was analyzed so far in 7 and 8 patients, respectively. We found a skewed T-cell repertoire with oligoclonal T-cell expansions to day 100 and normalization after day 200. An increased natural cytotoxicity receptor (NKP30, NKP44, NKP46) and NKG2A, but decreased NKG2D and KIR-expression was observed on NK-cells until day 100. In conclusion, T- and B-cell reconstitution is delayed after HHCT using CD3/CD19 depleted grafts and RIC. However, T-cell reconstitution is faster compared to data published with CD34 selected grafts and myeloablative conditioning. A fast NK-cell reconstitution early after HHCT was observed. Thus a combination of reduced intensity conditioning with CD3/CD19 depleted grafts appears to accelerate the immune recovery after haploidentical stem cell transplantation.

Natural Killer Cell Immune Reconstitution Predicts Outcomes for Patients with Chronic Lymphocytic Leukemia Undergoing Allogeneic Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3300-3300
Author(s):  
Don Benson ◽  
Leslie Andritsos ◽  
Mehdi Hamadani ◽  
Thomas Lin ◽  
Joseph Flynn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Immune Reconstitution ◽  
Nk Cell ◽  
Disease Status ◽  
Lymphocytic Leukemia ◽  
T Cell Subsets ◽  
Cell Recovery

Abstract Introduction: Chronic lymphocytic leukemia (CLL), the most common form of leukemia in the Western hemisphere, is associated with severe innate, adaptive and humoral immune dysregulation. CLL remains essentially incurable, with the potential exception of allogeneic stem cell transplantation (ASCT). Natural killer (NK) cells are CD56(+), CD3(−) large granular lymphocytes that comprise a key cellular subset of the innate immune system. Preliminary in vitro data suggest an NK cell versus CLL effect exists, similar to that observed in acute myeloid leukemia (AML) and other blood cancers. Novel immune therapies for CLL (e.g., rituximab, alemtuzumab) likely exert anti-tumor effect, in part, through NK cells, in fact. Although NK cells contribute to the graft-versus-tumor effect following ASCT for other blood cancers, little is known regarding the potential role NK cells may play in the clinical allogeneic transplant setting for CLL. Herein, we provide, to our knowledge, the first report regarding NK cell immune reconstitution following ASCT for CLL. Methods: 27 CLL patients underwent reduced intensity conditioning (RIC) with ASCT. Median age was 52 years (43–69), median number of prior therapies was 3 (2–11). 55% had chemotherapy-refractory disease, and 55% had “high-risk” cytogenetics by FISH (deletion 17p or 11q22-23 abnormality). 14 patients had sibling donors, 15 had volunteerunrelated donors. Conditioning regimens included Fludarabine/TBI/Alemtuzumab (n=8), Fludarabine/Busulfan with (n=9) or without ATG (n=6), and Fludarabine/Cyclophosphamide (n=4). GVHD prophylaxis consisted of tacrolimus/MMF (n=8) or tacrolimus/methotrexate (n=19). Patients underwent bone marrow assessment prior to day +75 following ASCT. Marrow was studied for engraftment, donor chimerism, and disease status as well as lymphoid immune reconstitution by percentage of total lymphocytes and absolute lymphocyte counts by multi-color flow cytometry. Results: NK cell immune reconstitution was predicted by disease status at transplantation. Patients in complete or partial remission at the time of ASCT had more robust NK cell recovery (mean = 45% of total lymphocytes +/− SEM 5%) as compared to patients entering transplant with refractory disease (16% +/− 1, p < 0.01). No differences were observed in CD4(+) or CD8(+) T cells and no lymphocyte subset recovery was associated with CD34(+) or CD3(+) cell dosage. Achieving complete donor chimerism by day +60 was associated with robust NK cell recovery (55% +/− 1 versus 7% +/−1, p = 0.02), recovery of CD4 and CD8 T cells was not associated with chimerism status, however. Patients who went onto exhibit a complete response to ASCT had greater early NK cell reconstitution (31% +/− 3) as compared to those who had no response (8% +/− 1, p = 0.01). No differences in T cell subsets were associated with response. Patients who ultimately achieved complete remission following transplant had a lower CLL:NK cell ratio in marrow (0.35 +/− 0.07) than those who did not (8.1 +/− 1, p = 0.01). However, differences in CLL:CD4(+) and CLL:CD8(+) T cells were not predictive of response. Trends to improvement in progression free survival and overall survival were observed for patients with NK cell reconstitution above the median for the group as compared to those below; no such trends were observed regarding T cell subsets. Greater NK cell reconstitution trended towards ultimate eradication of minimal residual disease following ASCT, but no such trends were observed for T cell subsets. Conclusions: Early NK cell recovery predicts survival following autologous and allogeneic SCT in a number of hematologic malignancies; however, little is known regarding this phenomenon in CLL. To our knowledge, these are the first findings to implicate a potentially important therapeutic role for early NK cell compartment recovery in CLL following ASCT. Further research into restoring and augmenting NK cell function following RIC/ASCT for CLL is warranted.

scholarly journals Tuberculosis but not Immune Reconstitution Inflammatory Syndrome (IRIS) prevents early and late NK cell degranulation reconstitution in HIV/TB co-infected patients

2011 ◽  
Vol 5 (S1) ◽  
Author(s):  
Polidy Pean ◽  
Eric Nerrienet ◽  
Yoann Madec ◽  
Laurence Borand ◽  
Sarin Chan ◽  
...  
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Nk Cell ◽  
Inflammatory Syndrome

Pilot Randomized Trial Comparing the Effects of Alemtuzumab and Cyclosporine Versus Tacrolimus, Methotrexate and Sirolimus on Graft Versus Host Disease Prevention, Engraftment and Immune Reconstitution After Reduced Intensity Unrelated Donor Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1245-1245
Author(s):  
Rachel B. Salit ◽  
Steven Z. Pavletic ◽  
Daniel H. Fowler ◽  
Jennifer Wilder ◽  
Kelly Bryant ◽  
...  
Keyword(s):  
Initial Data ◽  
Immune Reconstitution ◽  
Acute Gvhd ◽  
Nk Cell ◽  
Cell Recovery ◽  
Graft Versus Host ◽  
Grade Ii ◽  
Reduced Intensity ◽  
Grade Iii

Abstract Abstract 1245 A clearly superior graft-versus-host disease (GVHD) prophylaxis regimen has not been established for patients undergoing reduced intensity allogeneic hematopoetic stem cell transplantation (HSCT) from matched unrelated donors (URD). Encouraging results have been reported with both the combination of alemtuzumab plus cyclosporine (AC) (Chakraverty R et al Blood 2002) and the regimen of tacrolimus, methotrexate, and sirolimus (TMS) (Antin JH et al, Blood 2003) in the URD setting. These two regimens work by biologically distinct mechanisms and may have markedly different effects upon engraftment and immune reconstitution. As part of a randomized pilot study, we prospectively assessed the effects of the AC and TMS regimens on GVHD, engraftment, and immune reconstitution in the setting of targeted lymphocyte-depleting chemotherapy and reduced-intensity allogeneic HSCT from HLA-matched URD. Twenty patients (median age 53 yrs; range 24–70) with high risk hematologic malignancies (median prior regimens = 4; chemo-resistant disease = 35%) received disease-specific induction chemotherapy (DA-EPOCH-FR or FLAG) prior to transplantation for disease control and lymphocyte depletion. All patients then received conditioning with fludarabine 30 mg/m2/day × 4 days and cyclophosphamide 1200 mg/m2/day IV × 4 days followed by a T-cell replete mobilized peripheral blood allograft from a 10/10 HLA-matched URD. Patients were randomized at the time of enrollment to receive either: AC (n=10): alemtuzumab 20 mg/day IV over 8 hours Days -8 to -4 and cyclosporine starting at Day -1 with a 10% per week taper starting at Day +100 or TMS (n=10): tacrolimus and sirolimus starting at Day -3 with a 33% taper at Day +63 and Day +119 and methotrexate 5 mg/m2 IV, days +1, +3, +6, and +11. Treatment related mortality at Day +100 and 1 year for all 20 patients was 5% and 17% respectively. Actuarial event free and overall survival at 1 year after transplantation were 70% and 85% respectively; cumulative incidence of relapse at 1 year was 15%. There were no graft rejections on either arm. Median CD3+ chimerism in the AC vs TMS group was 86% vs 99% at Day+14 (p=0.025), 100% vs 98% at Day+28 (p=0.63) and 100% in both groups at Day+100 (p=0.83). Median CD14+/15+ chimerism in the AC vs TMS group was 93% vs 100% at Day+14 (p=0.020), 99% vs 100% at Day +28 (p=0.12) and 100% in both groups at Day +100 (p=0.89). The overall incidence of acute GVHD in the AC arm was 30% (Grade II-IV = 20%; Grade III-IV = 10%) and 40% in the TMS arm (Grade II-IV = 20%, Grade III-IV = 10%). With a median follow-up of 18 months, chronic GVHD was seen in 70% of patients in the AC arm (mild =10%, moderate = 40%, severe = 20%) and 60% in the TMS arm (moderate = 40%, severe = 20%). Patients on the AC arm had significantly less T-lymphocyte recovery by Day +14 compared with the TMS arm (median CD3+ = 1 cells/μl vs 356 cells/μl; CD4+ = 0 cells/μl vs 243 cells/μl; CD8+ = 0 cells/μl vs 59 cells/μl; each p<0.0001); this was less disparate at Day +28 (median CD3+ = 45 cells/μl vs 398 cells/μl; CD4+ = 36 cells/μl vs 218 cells/μl; CD8+ = 5 cells/μl vs 152 cells/μl; each p≤0.002). By Day +100, lymphocyte recovery was not appreciably different between the two groups (median CD3+ = 242 cells/μl vs 445 cells/μl CD4+ = 106 cells/μl vs 212 cells/μl, CD8+ = 72 cells/μl vs 135 cells/μl; each p>0.03). NK-cell recovery was slightly less in the AC arm compared with the TMS arm at Day +14 (median NK = 14 cells/μl vs 70 cells/μl; p=0.01) and at Day +28 (median NK = 29 cells/μl vs 150 cells/μl; p=0.02). There was no difference by Day +100 (median NK = 124 cells/μl vs 88 cells/μl; p=0.31). B-cell reconstitution was negligible in both groups up through Day +100. At median 18 month follow-up, patients treated on the AC arm had experienced a total of 28 episodes of Grade III-IV infections compared with 23 episodes on the TMS arm. These initial data suggest that AC and TMS provide approximately equivalent GVHD prevention and comparable time to full donor chimerism. However, the AC regimen was associated with later lymphocyte and NK cell recovery and a higher number of infectious episodes, raising a potential concern for increased infection risk with the AC regimen. It is also notable that despite delayed lymphocyte recovery in the AC arm, there were still comparable rates of acute GVHD with the TMS arm. Based on these initial data, we have expanded patient accrual and extended enrollment to recipients of HLA-mismatched URD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Characterization of Peripheral Blood Mononuclear Cells Addback Following CD34 Enrichment, Engraftment and T and NK Cells Immune Reconstitution in Patients with High Risk Sickle Cell Disease (SCD) (IND 14359)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-21
Author(s):  
Yaya Chu ◽  
Julie-An Talano ◽  
Lee Ann Baxter-Lowe ◽  
Carolyn A. Keever-Taylor ◽  
Erin Morris ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Nk Cells ◽  
Board Of Directors ◽  
Research Funding ◽  
Immune Reconstitution ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Advisory Committees ◽  
Hla Dr

Background: CD3/CD19 cell depletion (Barfiled RC, et al, Cytotherapy, 2004), αβ T-cell/CD19 cell depletion (Locatelli F, et al, Blood, 2017), CD34+ positive selection (Aversa F, et al, NEJM, 1998) are designed to deplete T cells and reduce AGVHD following allogeneic stem cell transplantation (AlloSCT). These approaches achieved low rates of AGVHD, but the grafts had few T and B cells. To improve immune reconstitution we undertook an alternative approach to addback small numbers and percentages of immune cells in the final HSCT product. We previously reported a very low incidence of AGVHD in pediatric recipients receiving CD34 enriched HPC products with peripheral blood mononuclear cells (PBMNC) addback containing a fixed dose of 2 x 105 CD3/kg from MUD donors (Geyer/Cairo et al, BJH, 2012). Recently we demonstrated that despite a 5 log depletion of T cells, PBMNC addback (fixed at 2 x 105 CD3/kg) facilitated rapid hematopoietic engraftment, high levels of donor chimerism and immune reconstitution with a low probability of Grade II-IV AGVHD. Patients had a 1 yr OS of 90% following familial haploidentical (FHI) CD34 Enriched Stem Cell Transplantation in patients with SCD (Cairo, JAMA Pediatr, 2020). Objective: To determine the final immune cell concentration following CD34 enrichment and PBMNC (2 x 105 CD3/kg) addback and determine the effect on engraftment and T and NK cell immune reconstitution. Methods: Patients and/or their guardians signed written informed consents and/or assents (NCT NCT02675959). CD34+ enrichment was performed using a CD34+ reagent system (CliniMACS; Miltenyi Biotec). Mononuclear cells (2 × 105 CD3 cells/kg of recipient body weight) were removed from the leukapheresis collection prior to CD34+ enrichment and were cryopreserved as a source of MNC addback (T cells). The addback products were analyzed for CD3+CD56- T cells, CD3-CD56+ NK cells, CD3+CD56+ NKT cells, Lin-CD123+ HLA-DR+ DC cells and Lin-CD11c+ HLA-DR+ DC cells by multicolor flow cytometry analysis. Th1/Th2 cytokines were measured by multiplex assays. T cell activity was measured by viral T cells IFN-g and plasma cytokines. NK function was measured by NK receptor expression by flow cytometry analysis and in vitro cytotoxicity. Results: We identified in the PBMNC addback, mean+SEM white blood cell (WBC) percentage of: CD3+ CD56- T cells = 56.4±5%; CD3- CD56+ NK cells = 4.6±1%; CD3+ CD56+ NKT cells = 5.1±0.6%; CD19+ B cells = 29.9±3.5%. Lin- WBC consisted of: CD123+ HLA-DR+ DC cells = 18.4±8.2%; CD11c+ HLA-DR+ DC cells = 6.0±3.0%. There were 20.0+9.1e6 T cells, 1.1+0.3e6 NK cells, 1.6+0.7 e6 NKT cells, 8.6+2.5e6 B cells, 1.2+0.6e6 CD123+DC and 0.8+0.5e6 CD11c DC in the final infused products (Fig.1). We found that percentages of IFN-g+ in CD4 cells in response to CMV (pp65), ADV (hexon) and EBV (BZLF1), ranged from 0.2%+0.1% to 0.5%+0.1%, while percentages of IFN-g+ in CD8 cells in response to the antigens ranged from 0.7%+0.3% to 3.7%+1.8% when examined at days 180, 270 and 365. NK (CD3- CD56+) reconstitution was extremely rapid and occurred as early as day 30 (35.5±8.6%, 2710+1624.4 cells/ul total cells; p&lt;0.01 vs pre-t). There were no significant differences pre-HSCT vs day 365 in plasma cytokines (Th1 and Th2) and growth factors released including IFN-g, TNF-a, IL-18, IL-4, IL-5, IL-6, IL-10, G-CSF, MCP-1 and MIP1a. There was also robust expression of NK receptor expression including NK cytotoxicity receptors, NK KIR receptors, and C-type lectin-like receptors at day 30 as compared to pre-HSCT. NK cytotoxicity, as measured using PBMC cells from recipients at different time points against K562 (E:T=10:1), was also significantly increased at day 30 (26.2±2.8%) and day 180 (28.3±3%) vs pre-HSCT (16.1±2.1%) (p&lt;0.01). As a NK cell activation marker, CD107a expression and granzyme B levels in gated NK cells peaked at day 30. Conclusion: PBMNC addback to CD34 enriched HPC products, with a final dose of 2 × 105 CD3 cells/kg, led to stem cell products with a diverse mixture of T, NK, NKT, DC1, and DC2 cells. Immune reconstitution following PBMNC addback to CD34 enriched cells resulted in excellent CD4 and CD8 responses to CMV, ADV and EBV, and rapid functional NK cell reconstitution (Supported by FDA R01FD004090 (MSC)). Disclosures Baxter-Lowe: CHLA: Current Employment, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Patents related to HLA typing, Research Funding. Johnson:Miltenyi Biotec: Research Funding; Cell Vault: Research Funding. Cairo:Miltenyi: Research Funding; Technology Inc/Miltenyi Biotec: Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Nektar Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Favorable Transplantation Outcomes Associated with Early Recovery of Lymphocytes and CD8+ Cells Following Allogeneic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4665-4665
Author(s):  
Joon Ho Moon ◽  
Yoon Young Cho ◽  
Byung Woog Kang ◽  
Shi Nae Kim ◽  
Soo Jung Lee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Immune Reconstitution ◽  
Nk Cell ◽  
Conflicts Of Interest ◽  
Cell Recovery ◽  
Early Recovery ◽  
Cd8 Cells

Abstract Abstract 4665 Background Immune reconstitution is an important component for successful transplantation. The laboratory parameters regarding immune reconstitution at 3 months after allogeneic stem cell transplantation (SCT) were analyzed in the current study. Methods To assess the kinetics of lymphocyte subset recovery, 128 patients who underwent allogeneic SCT and survived at least 3 months after transplantation were monitored by surface markers (CD3, CD4, CD8, CD19, CD56). Results Factors affecting CD4+ cell recovery at 3 months after transplantation included the use of cyclosporine instead of tacrolimus (odds ratio [OR]=0.256, p=0.007), in vivo T-cell depletion (OR=0.263, p=0.001), and use of peripheral blood stem cells instead of bone marrow (OR=0.281, p=0.016). The overall survival (OS) was better for the patients with early recovery of absolute lymphocyte counts (ANC, >1500/mm3), CD3+ (>1000/mm3), CD4+ (>300/mm3), CD8+ (>600/mm3), and CD19+ cells (>30/mm3). But CD56+ NK cell recovery (>300/mm3) failed to predict better survival. The patient group with early recovery of ANC, CD3+, and CD19+ cells showed a lower relapse rates. Treatment related mortality (TRM) was lower for the patients with early recovery of ANC, CD3+, and CD4+ cells. Chronic graft-versus-host disease (GVHD) was not related with the lymphocyte recovery. In the multivariate analysis, high risk disease status (hazard ratio [HR]=1.903, p=0.031), acute GVHD ≥grade 2 (HR=1.975, p=0.039), and HLA mismatch (HR=4.124, p=0.002) were significantly associated with lower OS, whereas, early recovery of ANC (HR=0.455, p=0.047) and CD8+ cells (HR=0.485, p=0.057) at 3 months showed a better survival. Conclusion Faster lymphocyte recovery and CD8+ cell recovery at 3 months after allogeneic SCT showed a better survival and lower TRM rate. Disclosures: No relevant conflicts of interest to declare.

Reduced Toxicity Conditioning (RTC) Compared to Myeloablative Conditioning (MAC) Prior to Unrelated Cord Blood Transplantation (UCBT) in Pediatric Recipients Was Associated with Similar but Also Delayed Time to Immune Reconstitution and a Concomitant Significant Decrease in Grade II-IV Agvhd.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2304-2304
Author(s):  
Jason Freedman ◽  
Diane George ◽  
Judith Jacobson ◽  
Mark Geyer ◽  
Carmella van de Ven ◽  
...  
Keyword(s):  
Immune Reconstitution ◽  
Acute Gvhd ◽  
Nk Cell ◽  
Cord Blood Transplantation ◽  
Lymphocyte Subset ◽  
Post Transplant ◽  
Blood Transplantation ◽  
Grade Ii ◽  
Reduced Toxicity ◽  
Immunoglobulin Levels

Abstract Abstract 2304 Poster Board II-281 Introduction. Immune reconstitution in pediatric transplant recipients appears to take longer following myeloablative conditioning (MAC) and umbilical cord blood transplantation (UCBT) than following matched sibling allogeneic stem cell transplantation (AlloSCT) (Parkman et al., BBMT, 2006). Reduced toxicity conditioning (RTC) is associated with less transplant-related morbidity and mortality than MAC prior to AlloSCT although the effects of RTC on long-term immune reconstitution in UCBT recipients are unknown (Satwani, Cairo et al., BBMT, 2005). We previously demonstrated sustained donor chimerism following RTC and UCBT in pediatric recipients (Bradley, Cairo et al., BMT, 2007). Our group recently found no significant difference between MAC and RTC in time to engraftment or donor chimerism in pediatric UCBT recipients; RTC was associated with decreased transplant-related mortality (TRM) and improved overall survival (OS) (Cairo et al., ASBMT, 2009). Objective. We analyzed time to immune reconstitution and associated risk factors in pediatric patients receiving RTC vs. MAC prior to UCBT. Methods. We evaluated immune reconstitution in 88 consecutive pediatric UCBT recipients with transplant dates between March 2000 and October 2008. Absolute CD3, CD4, CD8, CD19, and CD56 cell counts and IgG, IgA, and IgM levels were assessed using FACS analysis and ELISA, respectively, at days 100, 180, and 365 post-transplant. Predictors of grade II-IV acute GVHD, lymphocyte recovery, and malignant recurrence were analyzed using chi-square or Fisher's exact tests and multivariable logistic regression models. Results. The median age of the 88 patients was 6.5 years (range 0.25-22); 59% male/41% female, 56% MAC/44% RTC, HLA match 19% 6/6, 28% 5/6, 52% 4/6, 93% unrelated/7% related, 66% malignant/34% non-malignant, median TNC x107/kg 3.76 (range 0.9-22.61), and median CD34 ×107/kg (range 0.34-9.57). Mean (±SD) absolute lymphocyte subset counts (cells/μL), immunoglobulin levels (mg/dL) and sample sizes at days 100, 180, and 365 post-transplant are shown in Tables 1 and 2, respectively. At day 180, NK cell levels were slightly higher in the MAC group (310.0±212 vs. 171.3±83, p=0.05). Otherwise, MAC and RTC did not differ with respect to absolute lymphocyte subset counts or immunoglobulin levels. Other variables not associated with T-, B- and NK-cell reconstitution include grade II-IV acute GVHD, ATG/Campath conditioning, viral/fungal infection, and TNC/CD34 dose/kg. Lymphocyte subset counts and immunoglobulin levels were assessed as being normal or low according to age-specific reference ranges and did not differ significantly between MAC and RTC groups. Of 88 subjects, 24 (27.3%) developed grade II-IV acute GVHD. In a logistic regression model that included conditioning regimen (MAC vs. RTC), risk (average vs. poor), HLA-matching (4/6 vs. 5-6/6), CMV status (donor/recipient -/- vs. other), and time period (before 2005 vs. after 2004) to analyze predictors of grade II-IV GVHD, MAC recipients had a significantly higher risk of grade II-IV acute GVHD (odds ratio 4.43, p=.01), and of viral infection (odds ratio 3.86, p=.02) than RTC recipients. Malignant relapse occurred in 12 of 34 MAC recipients (35%) and 11 of 24 RTC recipients (46%). Conclusions. No significant differences between lymphocyte subset counts or immunoglobulin levels post-transplant were found with respect to MAC vs. RTC prior to UCBT. Children who received RTC had a significantly lower risk of grade II-IV acute GVHD than children who received MAC, when other risk factors were taken into account. These results support the continued use of RTC prior to UCBT for appropriate medical conditions. Disclosures: Bradley: Bristol-Myers Squibb Company: Employment.

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