Three Novel Clonal Non-Characteristic Chromosome Aberrations in Acute Myeloid Leukemia Resembling Acute Promyelocytic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4912-4912
Author(s):  
Hongxing Liu ◽  
Wenjun Tian ◽  
Fang Wang ◽  
Juan Zhu ◽  
Wen Teng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Chromosome Aberrations ◽  
Myeloid Leukemia ◽  
Cell Markers ◽  
Blood Tests ◽  
Hla Dr ◽  
D Dimer ◽  
Acute Myeloid

Abstract Abstract 4912 We report here three acute myeloid leukemia cases with novel clonal non-characteristic chromosome aberrations and morphologically resembling acute promyelocytic leukemia (APL). Case No.1: A 57-year-old woman came with mucosal bleeding, ecchymoses, and fever. Blood tests showed hemoglobin (Hb) of 9.3g/dL, platelet count (Plt) of 29×109/L and white blood cell count (WBC) of 1.3×109/L. D-dimer was 3.6ug/ml and Fibrin degradation product (FDPs)>5ug/ml. Bone marrow (BM) morphology showed 91% atypical hypergranular cells with Auer rods and resembling APL. The immunophenotype of peripheral blood (PB) blasts showed 83% positive for CD9, CD13, CD15, CD33, CD64, CD117 and negative for CD34, HLA-DR and B, T-cell markers. PML-RARA and t(15;17) negative but clonal t(1;16)(q44;q22) positive. The patient was initially treated with all-trans retinoic acid (ATRA), As4S4 and mitoxantrone and then switched to harringtonine and ara-C treatment but couldn't get remission. Case No.2: A 39-year-old woman came with asthenia, mucosal bleeding and ecchymoses. Blood tests showed Hb of 10g/dL, Plt of 49×109/L and WBC of 6.2×109/L. D-dimer >20ug/ml and FDPs >20ug/ml. BM morphology showed 84% atypical hypergranular cells with Auer rods and resembling APL. The immunophenotype of PB blasts showed 76% positive for CD13, CD33, CD64, CD117, cMPO and negative for CD9, CD34, HLA-DR and B, T-cell markers. PML-RARA and t(15;17) negative but clonal t(7;17)(p10;q10) positive. The patient was initially treated with ATRA and As4S4 and mitoxantrone but couldn't get a good response. He was then switched to idarubicin and ara-C treatment and got partial response. He is now waiting for allogeneic hematopoietic stem cell transplantation. Case No.3: A 62-year-old man came with asthenia. Blood tests showed Hb of 68 g/dL, Plt of 61×109/L and WBC of 3.3×109/L. D-dimer was 10.2ug/ml and FDPs was not tested. Bone marrow (BM) morphology showed 63.5% atypical hypergranular cells with Auer rods and resembling APL. The immunophenotype of Bone marrow showed 71.2% positive for CD13, CD15, CD33, CD117, cMPO and negative for CD34, HLA-DR,and B, T-cell markers. PML-RARA and t(15;17) negative but clonal (47,XY,+mar1) positive. The patient was initially treated with ATRA and As4S4 but couldn't get a good response. He was then swiched to Daunorubicin and ara-C treatment and got partial remission. APL should be distinguished from other subtypes of acute myeloid leukemia (AML) because of the increased risk of disseminated intravascular coagulation (DIC) and its response to ATRA and arsenic compounds. Some cases of AML seem morphologically similar to APL but lack the characteristic t(15;17) or other RARA-related translocations, and they generally didn't response to ATRA and arsenic compounds treatment. The 3 cases reported here reiterate the lack of specificity of morphologic and Immunophenotyping findings in APL-like AMLs. Karyotypic analysis, as well as FISH and RT-PCR, must be conducted on these cases to rule out APL and other chemotherapy regimens should be considered. APL-like AMLs that do not demonstrate RARA-related translocations may constitute a heterogeneous population of AML with diverse clonal non-characteristic chromosome aberrations, and the molecular mechanisms is worthy of further study. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Immunomodulatory Effect of Green Tea Treatment in Combination with Low-dose Chemotherapy in Elderly Acute Myeloid Leukemia Patients with Myelodysplasia-related Changes

2021 ◽  
Vol 20 ◽  
pp. 153473542110026
Author(s):  
Andrana K. Calgarotto ◽  
Ana L. Longhini ◽  
Fernando V. Pericole de Souza ◽  
Adriana S. Santos Duarte ◽  
Karla P. Ferro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Green Tea ◽  
Regulatory T Cell ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Related Factor ◽  
Low Dose Chemotherapy ◽  
Acute Myeloid

Green tea (GT) treatment was evaluated for its effect on the immune and antineoplastic response of elderly acute myeloid leukemia patients with myelodysplasia-related changes (AML-MRC) who are ineligible for aggressive chemotherapy and bone marrow transplants. The eligible patients enrolled in the study (n = 10) received oral doses of GT extract (1000 mg/day) alone or combined with low-dose cytarabine chemotherapy for at least 6 months and/or until progression. Bone marrow (BM) and peripheral blood (PB) were evaluated monthly. Median survival was increased as compared to the control cohort, though not statistically different. Interestingly, improvements in the immunological profile of patients were found. After 30 days, an activated and cytotoxic phenotype was detected: GT increased total and naïve/effector CD8+ T cells, perforin+/granzyme B+ natural killer cells, monocytes, and classical monocytes with increased reactive oxygen species (ROS) production. A reduction in the immunosuppressive profile was also observed: GT reduced TGF-β and IL-4 expression, and decreased regulatory T cell and CXCR4+ regulatory T cell frequencies. ROS levels and CXCR4 expression were reduced in bone marrow CD34+ cells, as well as nuclear factor erythroid 2–related factor 2 (NRF2) and hypoxia-inducible factor 1α (HIF-1α) expression in biopsies. Immune modulation induced by GT appears to occur, regardless of tumor burden, as soon as 30 days after intake and is maintained for up to 180 days, even in the presence of low-dose chemotherapy. This pilot study highlights that GT extracts are safe and could improve the immune system of elderly AML-MRC patients.

Constitutively Active AKT Induces Myeloproliferative Disease, Acute Myeloid Leukemia, and T Cell Lymphoma despite Impaired Engraftment

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3793-3793
Author(s):  
Kira Gritsman ◽  
Michael G Kharas ◽  
D. Gary Gilliland
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Myeloid Leukemia ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Akt Pathway ◽  
Myeloproliferative Disease ◽  
Constitutive Activation ◽  
Acute Myeloid

Abstract The phosphoinositide 3-kinase (PI3K)/AKT pathway is commonly dysregulated in human malignancies, including leukemia. AKT, a downstream effector of PI3K, is constitutively phosphorylated in myeloproliferative disease (MPD) and acute myeloid leukemia (AML) patient samples, suggesting that the PI3K/AKT pathway may be an attractive therapeutic target. In myeloid malignancies, this pathway is most commonly activated not by mutations in PI3K, AKT or loss of PTEN, but rather by mutations in a spectrum of upstream tyrosine kinases, such as BCR-ABL, ETV6-PDGFRb, FIPL1-PDGFRa, JAK2V617F, or FLT3-ITD. To further understand the contribution of PI3K/AKT activation to disease pathogenesis, we modeled the activation of AKT in myeloid neoplasms by such upstream effectors using a myristoylated allele of AKT (myr-AKT) that is constitutively activated. Bone marrow from 5-fluorouracil-primed C57 Bl/6 donor mice was transduced with a bicistronic retrovirus expressing myr-AKT and enhanced green fluorescent protein (EGFP) or control retrovirus expressing EGFP alone, and transplanted into 30 and 5 lethally irradiated syngeneic recipients, respectively. The myr-AKT transplant recipients had a median survival of 53 days. Of 30 myr-AKT mice, 27 (90%) developed a myeloproliferative disease (MPD), characterized by splenomegaly, hepatomegaly, expanded Mac1+Gr1+, Mac1+ckit+, and CD71+Ter119+ populations in the bone marrow and spleen, and increased splenocyte myeloid colony formation. Of these 27 myr-AKT mice with MPD, 19 (70%) also had thymic T cell lymphoma, characterized by infiltration of the thymus, heart, lungs, and muscle with CD4+/CD8+ lymphoblasts. Three of 30 (10%) myr-AKT mice developed acute myeloid leukemia (AML) with phenotypic attributes of erythroleukemia (AML M6) in humans, characterized by infiltration of the spleen, liver and bone marrow with CD71hickit+ blasts. Control EGFP recipients had no evidence of disease. Splenocytes from mice with AML and thymocytes from mice with T cell lymphoma caused disease when transplanted into secondary recipients, whereas splenocytes from mice with MPD were unable to transplant disease. Of note, we observed that myr-AKT expression caused impaired engraftment in recipient mice, as evidenced by a decrease in the %EGFP in the bone marrow over time. Although myr-AKT expressing cells can home normally to the bone marrow, myr-AKT significantly impairs the lodging ability of transduced bone marrow in irradiated recipients by 2 weeks after transplant. Furthermore, we observed an increased rate of apoptosis in myr-AKT-expressing bone marrow and spleen cells in myr-AKT recipient mice. Taken together, these data suggest that constitutive activation of AKT paradoxically increases apoptosis and impairs engraftment of transduced cells, but demonstrate that constitutive activation of AKT alone nonetheless recapitulates the spectrum of human myeloid neoplastic phenotypes associated with activation of upstream tyrosine kinase effectors.

Improved Outcome With T-Cell–Depleted Bone Marrow Transplantation for Acute Leukemia

1999 ◽  
Vol 17 (5) ◽  
pp. 1545-1545 ◽  
Author(s):  
Franco Aversa ◽  
Adelmo Terenzi ◽  
Alessandra Carotti ◽  
Rita Felicini ◽  
Roberta Jacucci ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Antithymocyte Globulin ◽  
Lymphoblastic Leukemia ◽  
Acute Myeloid

PURPOSE: To eliminate the risk of rejection and lower the risk of relapse after T-cell–depleted bone marrow transplants in acute leukemia patients, we enhanced pretransplant immunosuppression and myeloablation. PATIENTS AND METHODS: Antithymocyte globulin and thiotepa were added to standard total-body irradiation/cyclophosphamide conditioning. Donor bone marrows were depleted ex vivo of T lymphocytes by soybean agglutination and E-rosetting. This approach was tested in 54 consecutive patients with acute leukemia who received transplants from HLA-identical sibling donors or, in two cases, from family donors mismatched at D-DR. No posttransplant immunosuppressive treatment was given as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Neither graft rejection nor GVHD occurred. Transplant-related deaths occurred in six (16.6%) of 36 patients in remission and in seven (38.8%) of 18 patients in relapse at the time of transplantation. The probability of relapse was .12 (95% confidence interval [CI], 0 to .19) for patients with acute myeloid leukemia and .28 (95% CI, .05 to .51) for patients with acute lymphoblastic leukemia who received transplants at the first or second remission. At a median follow-up of 6.9 years (minimum follow-up, 4.9 years), event-free survival for patients who received transplants while in remission was .74 (95% CI, .54 to .93) for acute myeloid leukemia patients and .59 (95% CI, .35 to .82) for acute lymphoblastic leukemia patients. All surviving patients have 100% performance status. CONCLUSION: Adding antithymocyte globulin and thiotepa to the conditioning regimen prevents rejection of extensively T-cell–depleted bone marrow. Even in the complete absence of GVHD, the leukemia relapse rate is not higher than in unmanipulated transplants.

Aberrant expression of T-cell markers in acute myeloid leukemia

2007 ◽  
Vol 83 (3) ◽  
pp. 462-463 ◽  
Author(s):  
Robert E. Lewis ◽  
Julius M. Cruse ◽  
Catherine M. Sanders ◽  
Rachel N. Webb ◽  
Jeanann L. Suggs
Keyword(s):  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Myeloid Leukemia ◽  
Aberrant Expression ◽  
Cell Markers ◽  
Acute Myeloid

scholarly journals Histone Hypoacetylation-Driven CD9 Repression Arrests Differentiation and Evades Immunosurveillance in Pediatric Acute Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3311-3311
Author(s):  
Yaqun Xu ◽  
Kathy Chan ◽  
Siu Ping Fok ◽  
Toni Ki Fong Man ◽  
Chi Kong Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Myeloid Leukemia ◽  
Survival Duration ◽  
Prognostic Impact ◽  
Mhc I ◽  
Presentation Pathway ◽  
Pediatric Aml ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a genetically heterogeneous hematologic malignancy characterized by uncontrolled proliferation of myeloid progenitor cells accompanied by impaired terminal differentiation. Despite intensive treatment regimes, the clinical outcomes remain poor, underscoring the need to decipher the underlying pathology and implement therapeutic interventions. Emerging evidence suggest myeloblasts could evolve machineries to evade T cell patrol and hinder immunotherapies. Here, we present a new mechanism driving immune escape in the context of pediatric AML, based on our discoveries of CD9 in hematopoietic stem cells (HSC; Leung et al, Blood, 2011) and acute lymphoblastic leukemia (ALL; Leung et al, Leukemia, 2020). We first examined CD9 expression and its prognostic impact in patient cohorts of childhood leukemia. The expression of cell surface CD9 on blasts of pediatric AML patients (13.2%, n=81) was significantly lower than that of pediatric ALL patients (90.4%, n=181, P<0.001) or that on CD34+ HSC of normal bone marrow donors (48.4%, n=22, P=0.014). Among pediatric AML cases, the blasts of 32 patients (39.5%) were CD9+. The 5-year RFS rate of CD9- patients was significantly lower than CD9+ patients (34.1% vs. 61.2%, P=0.018). Enforced CD9 expression in MV4-11 cells significantly suppressed proliferation (P<0.01), Ki-67 expression (P=0.041) and colony formation (P=0.002). NOD/SCID mice transplanted with CD9+ cells exhibited a drastic reduction of leukemic load in the bone marrow, spleen, blood and liver by 70.7-91.8% (P<0.05), a significantly prolonged survival duration (P<0.001), and a marked regression of extramedullary myeloid sarcoma when compared with animals transplanted with CD9- MV4-11 cells. A marked decrease of H3K9/27Ac occupancy in the CD9 locus was observed in AML than in ALL cells (4.8-14.2-fold, P<0.05), and strongly correlated with CD9 repression (r=0.585-0.719, P<0.01). Exposure of CD9- AML cell lines (n=8) and samples (n=9) with a histone deacetylase inhibitor panobinostat significantly elevated CD9 mRNA and protein expression (3.1-32.2-fold, P<0.05), restored activating histone acetylation marks (4.1-41.6-fold, P<0.05) and suppressed myeloblast proliferation ex vivo (median IC50: 21.4 nM). Mechanistically, global transcriptome profiling of pediatric AML (n=31) revealed decreased stemness (NES: -1.7, P=0.01) and increased monocyte (NES: 1.8, P=0.034) gene signatures in CD9+ patient samples. Moreover, single-cell transcriptomic analyses of total bone marrow cells from MV4-11-tranplanted mice detected a significant enrichment of differentially regulated genes functioning in the antigen processing and presentation pathway. Concordantly, we observed a profound up-regulation of CD9 (9.4-51.1-fold, P<0.001) in PMA-mediated monocyte/macrophage-like AML differentiation cultures preceding the appearance of lineage markers CD14, CD36 and iCD68 as well as the antigen presentation molecule MHC-I. In the overexpression system, CD9 not only elevated the expression of monocytic markers, but also promoted basal and IFNγ-induced MHC-I/II expression (P<0.01) through the JAK/STAT axis. Inter-patient comparisons of bone marrow samples (n=27) revealed a higher MHC-I expression in CD9+ than CD9- AML (MFI: 61820 vs. 18601, P<0.001). Interestingly, tetraspanin CD9 physically bound to MHC-I/II and formed an immune complex as revealed by co-immunoprecipitation. In NSG mice, co-transplantation of human PBMCs mounted an effective immunity against CD9+ but not CD9- AML (MV4-11 and MOLM-13), concomitant with a robust bone marrow infiltration of cytotoxic T cells. Syngeneic transplantation in immunocompetent mice, AML/T cell co-cultures, antigen-specific assays and panobinostat priming/T cell adoptive transfer are currently underway to fully dissect the role of CD9 in leukemia immunity. Taken together, our data provided molecular, cellular and clinical evidence showing the plausible function of CD9 as a key driver intertwining differentiation and immunosurveillance in pediatric AML, and inspired a new combinatorial epigenetic/immunotherapy for this rare but aggressive malignancy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Identification and Isolation of Tumor-Specific Cytotoxic T Lymphocytes in Acute Myeloid Leukemia Patients through the Identification of T-Cells Capable to Establish Stable Interactions with Leukemic Cells

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3336-3336
Author(s):  
Estefania Garcia-Guerrero ◽  
Luis I. Sanchez-Abarca ◽  
Esther Domingo ◽  
Teresa Ramos ◽  
Jose Antonio Bejarano-García ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Myeloid Leukemia ◽  
Target Cells ◽  
Acute Myeloid

Abstract Introduction Autologous adoptive T cell therapies, based on the use of tumor infiltrating lymphocytes (TILs), have made great progress in recent years for the treatment of solid tumors, especially melanoma. However, further work is needed to isolate tumor-reactive T cells among patients diagnosed with hematologic malignancies. The dynamics of the interaction between T cells and antigen presenting cells (APC) dictate the quality of the immune responses. While stable joints between target cells and T lymphocytes lead to the induction of T cell activation and immune response, brief contacts contribute to the induction of immune-tolerance. Taking advantage of the strong interaction between target cell and activated T-cells, we show the feasibility to identify and isolate tumor-specific cytotoxic T lymphocytes (CTLs) from acute myeloid leukemia (AML) patients. Using this approach, CTLs stably bound through T cell receptor to tumor cells (doublet forming T-cells) can be identified in peripheral blood and bone marrow and subsequently selected and isolated by FACS-based cell sorting. Methods Co-cultures between PBMC from AML patients in complete remission and AML tumor cells (PKH-stained) from the same patient were performed to study the percentage of doublet-forming T cells (CD3+PKH+) (T cell bound to a tumor cell). After 15 hours of co-culture, cells were stained and sorted. Secondary co-cultures with autologous tumor cells (used in primary co-culture) were performed to study the cytotoxic activity and cytokine production of T-cells capable or not to form stable joints with the leukemic cells (doublet population vs non-doublet population). Results Doublet-forming T cells from AML patients were identified in a range of 2% to 6% (mean=3.83%, n=5). Immunophenotyping analysis showed differences between doublet-forming T cells (CD3+PKH+) and those T cells which did not form stable and strong interactions with target cells (CD3+PKH-). Doublet T cells displayed a higher percentage of CD8+ T cells and higher percentage of effector CD4+ and CD8+ T cells compared to non-doublet T cells. Next, we explored, among effector CD4+ and CD8+ cells, those with cytotoxic phenotype. As expected, a high percentage of effector CD8+ doublet T cells showed Granzyme B and perforin expression, thus corresponding with a cytotoxic immune-phenotype (n=3, mean 65.51%). Within effector CD4+ doublet T cells, a mean of 9.053 % showed expression of both Granzyme B and perforin corresponding with CD4+ CTL (n=3). Regarding CD57 and CD16 markers, a mean of 18.62% of effector CD4+ doublet T cells were positive for both markers, compared to 65.84% of effector CD8+ doublet T cells (n=3). Further, we performed secondary co-cultures to analyze the CD69 activation marker after 24h of co-culture. A high percentage of CD69+ cells was observed in co-cultures with doublet-forming T cells against target cells as compared to non-doublet T cells (n=3, p=0.0053). Finally, analysis of supernatants of co-culture of doublet T cells and non-doublet T cells with target cells revealed specific secretion of IFNγ and IL-2 (n=3, p=0.0001; p=0.0005, respectively). The cytolytic activity was evaluated comparing the viability of tumor cells cultured alone or with doublet-forming T cells or non-doublet T cells from the same patient. A significant increase of the specific lysis of AML cells was observed when doublet T cells were co-cultured as compared to non-doublet T cells (p=0.0424, n=5). This encouraged us to examine whether we were able to identify doublet-forming T cells from bone marrow of AML patients at diagnosis. Analyses of bone marrow by flow cytometry reveled a small percentage of CD3+CD34+ population corresponding with bone marrow-doublet-forming T cells (n=3, mean=2.9%). Interestingly, bone marrow-doublet-forming T cells show a higher percentage of CD4+ T cells, whereas bone marrow-non-doublet T cells show a higher percentage of CD8+ T cells. Conclusions Our data demonstrate that when T cells from AML patients are co-cultured with tumor cells, a "doublet T cell" population appears. This population consists of T cells capable to bind tumor cells. These CTLs display higher percentage of effector cells and a marked cytotoxic activity against AML blasts. In conclusion, we have developed a new procedure to identify and select specific cytotoxic T cells in both bone marrow and peripheral blood from patients diagnosed with acute myeloid leukemia. Figure. Figure. Disclosures Sanchez-Abarca: Virgen del Rocio University Hospital: Patents & Royalties. Ramos:Takeda Oncology: Research Funding.

Characterization of Immune Reconstitution Following High Dose Chemotherapy in Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3888-3888
Author(s):  
Christian F. Meyer ◽  
Christopher Thoburn ◽  
Ferdynand Kos ◽  
Christopher Gocke ◽  
Hyam I. Levitsky ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Immune Reconstitution ◽  
Consolidation Therapy ◽  
Time Points ◽  
Acute Myeloid

Abstract Recovery of immune function after initial treatment of acute myeloid leukemia (AML) is critical, not only for protection against infections but also for surveillance against recurrent disease. A better understanding of the nature of lymphocyte recovery following induction and consolidation therapy for AML could guide the design of immunotherapy strategies aimed at boosting the anti-leukemia activity of a reconstituted immune system. Prior studies examining thymic T cell production following bone marrow transplantation (BMT) have found varying levels of thymic output post-transplant, as measured by T cell Receptor Excision Circle (TREC) levels in the peripheral blood of adult patients. Of note, relapse of chronic myeloid leukemia (CML) following BMT is correlated with decreased levels of TREC positive T cells. In order to characterize immune reconstitution in AML, we studied 26 patients after induction or consolidation time sequential chemotherapy. Their median age was 52 (range 23–69). Thirteen patients received cytarabine, daunorubicin, and etoposide (AcDVP-16) induction therapy, 3 patients received cytarabine, daunorubicin, and cytarabine (AcDAc) consolidation therapy and 10 patients received flavopiridol, cytarabine, and mitoxantrone (FLAM) either as induction or consolidation therapy. Peripheral blood samples were collected approximately every other day for 3–5 time points after each patient’s white blood cell count exceeded 200 cells/cubic mm on three consecutive days. Among the four patients evaluated to date, flow cytometry results show that a majority of cells seen early in immune reconstitution are CD3+ lymphocytes (range 69–97%). Subset analyses on 3 of these 4 patients have shown CD4:CD8 ratios ranging from 3:1 to 4:1, while the fourth patient exhibited an inverse of this ratio at 1:5. In addition, CD25+FOXP3+ T cells represented a median of 5.1% (range 2.5–12.3%) of the CD3+ T cells. Since T cells represented the abundance of cells in the peripheral blood during early bone marrow recovery, we then assessed whether these cells represented recent thymic emigrants or naïve T cells by examining TRECs using real time PCR (RT-PCR). TRECs were present in 24 of the 26 patients with levels ranging between 100 and 100,000 copies per 100,000 cells. Furthermore, 4 control samples from normal volunteers (ages 37–43) revealed the absence of TREC positive cells. Further analyses of these time points and correlations between TREC levels and clinical responses are ongoing.

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