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Pierre Tiberghien

Publications and source records attributed to Pierre Tiberghien.

At least 37 records · Page 2Linked to original sources
PubMed2004

Comparison of graft-versus-host-disease and survival after HLA-identical sibling bone marrow transplantation in ethnic populations.

The association of ethnicity with the incidence of graft-versus-host disease (GVHD) and other clinical outcomes after transplantation is controversial. We compared the results of HLA-identical sibling bone marrow transplantations for leukemia, performed between 1990 and 1999, among different ethnic populations, including 562 Japanese, 829 white Americans, 71 African Americans, 195 Scandinavians, and 95 Irish. Results for adults and children were analyzed separately. Multivariate analyses of adult patients showed that white Americans, African Americans, and Irish cohorts were at significantly higher risk for acute GVHD than Japanese or Scandinavian cohorts (relative risk [RR] = 1.77, P < .001; RR = 1.84, P < .006; RR = 2.22, P < .001, respectively). White Americans, African Americans, and Irish, but not Scandinavians, were at significantly higher risk for early (within 3 months of transplantation) transplant-related mortality (TRM) compared with Japanese (RR = 2.99, P < .001; RR = 5.88, P < .001; RR = 2.66, P < .009, respectively). No differences in the risk for chronic GVHD, relapse, and overall survival were noted. In the pediatric cohort (limited to Japanese and white Americans), white Americans were at significantly higher risk for acute (RR = 1.93; P = .04) and chronic (RR = 3.16; P = .002) GVHD. No differences in other clinical outcomes were noted. Our findings suggest that ethnicity may influence the risk for GVHD, though overall survival rates after transplantation remain similar.

Adult↗
PubMed2004

Expression of the myeloid-associated marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells.

A new entity of acute leukemia coexpressing CD4(+)CD56(+) markers without any other lineage-specific markers has been identified recently as arising from lymphoid-related plasmacytoid dendritic cells (pDCs). In our laboratory, cells from a patient with such CD4(+)CD56(+) lineage-negative leukemia were unexpectedly found to also express the myeloid marker CD33. To confirm the diagnosis of pDC leukemia despite the CD33 expression, we demonstrated that the leukemic cells indeed exhibited pDC phenotypic and functional properties. In 7 of 8 other patients with CD4(+)CD56(+) pDC malignancies, we were able to confirm that the tumor cells expressed CD33 although with variable expression levels. CD33 expression was shown by flow cytometry, reverse transcriptase-polymerase chain reaction, and immunoblot analysis. Furthermore, CD33 monoclonal antibody stimulation of purified CD4(+)CD56(+) leukemic cells led to cytokine secretion, thus confirming the presence of a functional CD33 on these leukemic cells. Moreover, we found that circulating pDCs in healthy individuals also weakly express CD33. Overall, our results demonstrate that the expression of CD33 on CD4(+)CD56(+) lineage-negative cells should not exclude the diagnosis of pDC leukemia and underline that pDC-specific markers should be used at diagnosis for CD4(+)CD56(+) malignancies.

Acute Disease↗
PubMed2004

A single-platform approach using flow cytometry and microbeads to evaluate immune reconstitution in mice after bone marrow transplantation.

The monitoring of immune reconstitution in murine models of HC transplantation, using accurate and automated methods, is necessary in view of the recent developments of hematopoietic cell (HC) transplantation (including reduced intensity conditioning regimens) as well as emerging immunological concepts (such as the involvement of dendritic cells or regulatory T cells). Here, we describe the use of a single-platform approach based on flow cytometry and tubes that contain a defined number of microbeads to evaluate absolute blood cell counts in mice. This method, previously used in humans to quantify CD34+ stem cells or CD4+ T cells in HIV infected patients, was adapted for mouse blood samples. A CD45 gating strategy in this "lyse no wash" protocol makes it possible to discriminate erythroblasts or red blood cell debris from CD45+ leukocytes, thus avoiding cell loss. Tubes contain a lyophilized brightly fluorescent microbead pellet permitting the acquisition of absolute counts of leukocytes after flow cytometric analysis. We compared this method to determine absolute counts of circulating cells with another method combining Unopette reservoir diluted blood samples, hemocytometer, microscopic examination and flow cytometry. The sensitivity of this single-platform approach was evaluated in different situations encountered in allogeneic HC transplantation, including immune cell depletion after different conditioning regimens, activation status of circulating cells after transplantation, evaluation of in vivo cell depletion and hematopoietic progenitor mobilization in the periphery. This single-platform flow cytometric assay can also be proposed to standardize murine (or other mammalian species) leukocyte count determination for physiological, pharmacological/toxicological and diagnostic applications in veterinary practice.

Animals↗
PubMed2004

Retrovirus-mediated gene transfer in human primary T lymphocytes induces an activation- and transduction/selection-dependent TCR-B variable chain repertoire skewing of gene-modified cells.

In a clinical trial that we recently reported, a suicide gene transfer in human primary T cells required 12 days of ex vivo culture, including activation of peripheral blood mononuclear cells (PBMC) with CD3 monoclonal antibody (CD3 mAb), retrovirus-mediated transduction, and selection of gene-modified cells (GMC) by G418. The aim of the present study was to determine the impact of the initial T cell activation and of the transduction/selection on T cell receptor beta variable chain (TCRBV) repertoire of GMC by using the spectratyping method. The TCRBV repertoires of nontransduced, nonselected control (Co) cells and of GMC generated after an initial stimulation with CD3 mAb, CD3/CD28 beads, or allogeneic PBMC or Epstein-Barr virus-transformed B (B-EBV) cells were compared to the ones of their corresponding PBMC. The TCRBV repertoires were skewed in Co cells generated after CD3 mAb or after allogeneic stimulation, and even more so in their corresponding GMC, demonstrating that both culture-dependent and transduction/selection-dependent events led to TCRBV repertoire alterations. However, TCRBV repertoires were not altered, or to a lesser extent, in Co cells or GMC produced after CD3/CD28 bead activation, demonstrating a protective effect on both culture-dependent and transduction/selection-dependent repertoire alterations. Thus, we suggest to replace the initial CD3 mAb stimulation by CD3/CD28 beads for the production of clinical-grade GMC in the setting of future gene therapy trials.

Antibodies, Monoclonal↗
PubMed2004

Intravenous infusion of apoptotic cells simultaneously with allogeneic hematopoietic grafts alters anti-donor humoral immune responses.

Intravenous infusion of apoptotic donor or third-party leukocytes simultaneously with an allogeneic donor bone marrow (BM) graft favors engraftment across major histocompatibility barriers. While verifying that such apoptotic cell infusion might not also be associated with antibody (Ab)-mediated allo-immune responses, we found, rather strikingly, that apoptotic cell infusion could in fact successfully prevent a humoral allo-immunization against a BM graft in mice. Indeed, among recipients having rejected their BM graft, prior apoptotic cell infusion was associated with a near absence of Ab-mediated allo-responses, while such an immunization was frequently observed in the absence of apoptotic cell infusion. This was also observed when infusing host apoptotic cells, thus showing that the prevention of immunization was linked to the apoptotic state of the cells rather than mediated by residual anti-recipient activity. In vivo anti-transforming growth factor-beta (TGF-beta) treatment resulted in the loss of this apoptotic cell infusion-associated protective effect on humoral allo-responses. Further studies will determine whether apoptotic cell infusion, in addition to hematopoietic graft facilitation might also contribute to preventing deleterious Ab-mediated allo-responses in various transplantation settings.

Animals↗
PubMed2003

Administration of donor apoptotic cells: an alternative cell-based therapy to induce tolerance?

Apoptotic cells are endowed with immunomodulatory properties. The authors propose infusing apoptotic cells as a cell-based therapy product to facilitate allogeneic hematopoietic engraftment after a nonmyeloablative conditioning regimen. Such an approach may be used to obtain macrochimerism in combined hematopoietic cells and solid organ transplantation. In this article, the authors describe the mechanisms of combined hematopoietic and organ allograft transplantation and the potential difficulties. The authors discuss how intravenous apoptotic cell infusion may influence the outcome of combined transplantation. This may prove to be an interesting approach for future development in cell therapy.

Animals↗
PubMed2003

How should chimerism be decoded?

To date, the significance of chimerism has not been fully understood. In particular, microchimerism can be associated with allograft acceptance or rejection. Several factors may influence the immunologic consequences of chimerism. In this review, the major factors influencing these consequences are briefly described. Subsequently, the different methods available for detecting and tracking donor-derived cells are listed. These techniques have been mainly developed concomitantly with nonmyeloablative hematopoietic allografts to monitor immunosuppression. Finally, the authors suggest how these methods may help to improve the understanding of microchimerism in solid organ transplantation.

Hematopoietic Stem Cell Transplantation↗
PubMed2003

Retrovirus-mediated gene transfer in polyclonal T cells results in lower apoptosis and enhanced ex vivo cell expansion of CMV-reactive CD8 T cells as compared with EBV-reactive CD8 T cells.

To modulate alloreactivity after hematopoietic stem cell transplantation, "suicide" gene-modified donor T cells (GMCs) have been administered with an allogeneic T-cell-depleted marrow graft. We previously demonstrated that such GMCs, generated after CD3 activation, retrovirus-mediated transduction, and G418 selection, had an impaired Epstein-Barr virus (EBV) reactivity, likely to result in an altered control of EBV-induced lymphoproliferative disease. To further characterize the antiviral potential of GMCs, we compared the frequencies of cytomegalovirus (CMV)-specific CD8+ T (CMV-T) cells and EBV-specific CD8+ T (EBV-T) cells within GMCs from CMV- and EBV-double seropositive donors. Unlike anti-EBV responses, the anti-CMV responses were not altered by GMC preparation. During the first days of culture, CMV-T cells exhibited a lower level of CD3-induced apoptosis than did EBV-T cells. In addition, the CMV-T cells escaping initial apoptosis subsequently underwent a higher expansion rate than EBV-T cells. The differential early sensitivity to apoptosis could be in relation to the "recent activation" phenotype of EBV-T cells as evidenced by a higher level of CD69 expression. Furthermore, EBV-T cells were found to have a CD45RA-CD27+CCR7- effector memory phenotype, whereas CMV-T cells had a CD45RA+CD27-CCR7- terminal effector phenotype. Such differences could be contributive, because bulk CD8+CD27- cells had a higher expansion than did bulk CD8+CD27+ cells. Overall, ex vivo T-cell culture differentially affects apoptosis, long-term proliferation, and overall survival of CMV-T and EBV-T cells. Such functional differences need to be taken into account when designing cell and/or gene therapy protocols involving ex vivo T-cell manipulation.

Antigens, CD↗
PubMed2003

Blood versus marrow hematopoietic allogeneic graft.

Allogeneic G-CSF-mobilized blood cell transplantation (BCT), an alternative to allogeneic bone marrow transplantation (BMT), is associated with enhanced engraftment and accelerated hematopoietic recovery. In addition, immune reconstitution and overall alloreactivity after BCT versus BMT differ significantly. Indeed, despite an increased number of donor T cells infused, the incidence of acute graft-versus-host disease (GvHD) after BCT appears to remain identical or lesser than after BMT. On the other hand, a higher risk of chronic GvHD has been reported after BCT. In a SFGM phase III trial, 101 patients with early leukemia and an HLA-matched sibling donor randomly received a BCT or BMT. BCT was associated with a higher number of infused CD34+ cells, accelerated platelet and neutrophil reconstitution, fewer platelet transfusions and similar acute GvHD incidence. However, chronic GvHD occurred more frequently after BCT. With a median follow-up of 20 months, relapse, survival and leukemia-free survival were not different. In the course of this study, immune parameters related to the graft as well as to early reconstitution were prospectively examined. T cells subsets, B cells, NK cells and monocytes numbers were significantly higher in BC grafts (versus BM). T cells in BC grafts were less activated than in BM grafts. Frequency of IFN-gamma, IL-2- and TNF-alpha-secreting cells and single-cell IFN-gamma production potential was reduced in BC graft. One month after BCT, blood T-cell counts were 3-fold higher than after BMT. Moreover, post-BCT T cells were less activated and counts correlated with the number of T cells infused with the graft, which was not the case after BMT. Several acute hemolysis episodes, resulting from anti-A and/or -B donor-derived Ab directed at Ag present on recipient red blood cells (minor ABO mismatch), have been described after BCT. Recipients indeed exhibited significantly increased anti-A and/or -B Ab titers after BCT, particularly in the setting of a "minor" ABO mismatch. Furthermore, the frequency of anti-HLA Ab early after BCT was significantly increased (despite the reduction in platelet transfusion requirements). The higher number of activated B cells and/or CD4 T cells and monocytes in a BCT graft and/or the higher number of circulating CD4 T- and B-cells after BCT could be associated with the enhanced alloAb production. G-CSF-induced TH2 cytokine profile of the T cells present in the graft could also be contributive. Recent studies have determined that BC grafts contained a higher number of type 2 dendritic cells (DC2), themselves associated with high frequencies of TH2 CD4+ cells. Since chronic GvHD is associated with the occurrence of Ab-mediated auto-immune-like syndromes, it is tempting to speculate that a higher incidence of chronic GvHD may result from these findings. In conclusion, BCT results in clinically relevant distinct hematopoietic and immune reconstitution patterns.

Antigens, CD34↗
PubMed2003

Decreased treatment failure in recipients of HLA-identical bone marrow or peripheral blood stem cell transplants with high CD34 cell doses.

We studied the association between CD34 cell dose and transplant outcomes in 359 bone marrow (BM) and 511 peripheral blood stem cell (PBSC) transplant recipients from human leucocyte antigen (HLA)-identical siblings, reported to the International Bone Marrow Transplant Registry (IBMTR). Transplants for leukaemia were performed between 1995 and 1998. Patients were divided into those receiving below or above the median CD34+ dose, for BM (3 x 106/kg) and PBSC (6 x 106/kg) grafts respectively. Cox proportional hazards regression was used to adjust for baseline patient-, disease- and transplant-related characteristics. Analysis of the BM recipients showed that high CD34 cell dose was associated with lower transplant-related mortality [relative risk (RR) = 0.60, P = 0.033] and treatment failure (inverse of leukaemia-free survival, RR = 0.69, P = 0.032). Among PBSC recipients, high CD34 dose was associated with faster recovery of neutrophils to > 0.5 x 109/l (RR = 1.38, P < 0.001) and platelets to > 20 x 109/l (RR = 1.34, P = 0.003), lower risk of relapse (RR = 0.62, P = 0.029) and treatment failure (RR = 0.74, P = 0.03). We conclude that higher CD34 cell doses decrease treatment failure in recipients of HLA-identical sibling BM and PBSC transplants.

Acute Disease↗
PubMed2003

A single intravenous infusion of apoptotic cells, an alternative cell-based therapy approach facilitating hematopoietic cell engraftment, did not induce autoimmunity.

Previously, we reported that intravenous infusion of apoptotic leukocytes facilitated bone marrow (BM) engraftment across major histocompatibility barriers. This cell-based therapeutic approach is of great interest for stem cell therapy across histocompatibility barriers. Autoimmunity associated with apoptotic cell administration may, however, limit the use of this approach. Indeed, autoantigens are concentrated on the surface of apoptotic cells, and defective clearance of apoptotic bodies is associated with the occurrence of systemic autoimmune disease. In consequence, we assessed the autoimmune responses raised against ubiquitous double-stranded DNA (dsDNA) and cardiolipin autoantigens following a single intravenous infusion of apoptotic cells simultaneously to allogeneic BM administration. No difference was observed between levels of natural circulating immunoglobulin M (IgM) (anti-dsDNA and anti-cardiolipin) autoantibodies found in mice receiving allogeneic BM alone and those found in mice receiving apoptotic cells also. Pathogenic IgG autoantibody titers after apoptotic cell infusion were 9- to 200-fold lower than autoantibody titers found in lupus-prone mice and not different from titers detected in BM grafted mice. Kinetic analysis of autoantibodies after transplantation did not demonstrate any immunization against tested autoantigens after apoptotic cell infusion. Finally, neither immune complex deposition nor specific lesions were observed in the renal glomeruli of mice infused with apoptotic cells 9 months post-BM transplantation. Overall, these results show no specific toxicity of a single infusion of apoptotic cells administrated simultaneously to BM and may also shed light on factors influencing the immunogenic properties of apoptotic cells.

Animals↗
PubMed2003

Bacterial contamination of a cornea tissue bank: implications for the safety of graft engineering.

PURPOSE: To analyze the difficulties involved in managing an episode of bacterial contamination in a cornea bank. We describe (1) the circumstances of bacterial contamination discovery, (2) the methods used to investigate the outbreak, (3) the corrective measures adopted, and (4) the method introduced to improve the reaction capacity in case of bacterial contamination. METHODS: All the samples collected were cultured in an attempt to identify the environmental reservoir of the contaminated epidemic clone. Bacteria were identified by Gram stain, oxidase test, and biochemical characteristics. The clonality of the strains was assessed by pulsed-field gel electrophoresis. RESULTS: The bacterial contamination was confirmed for 28 corneas, and 70 additional corneas were discarded. The source of the contamination was identified 17 days after the beginning of the episode. It consisted of a clonal bacterial strain that was found in trypan blue, the dye, used to examine all the tissues. The contaminating bacterium was Burkholderia cepacia, a well-known nosocomial pathogen. A total of 169 grafted corneas had been checked with the contaminated reagent. No cases of post-graft infection were recorded. CONCLUSION: Trypan blue played a major role in this outbreak. The mode and chronology of contamination remain unresolved. This exceptional event emphasizes the risk of bacterial contamination in tissue/cell banks, the necessity to improve methods for its prevention, and procedures to limit its consequences.

Burkholderia Infections↗
PubMed2003

CD4 cell lymphopenia and atherosclerosis in renal transplant recipients.

Several animal studies suggest that T cell-mediated immunodeficiency may play a role in the progression of atherosclerosis. This study examined the association between lymphocyte subsets and atherosclerotic events in renal transplant recipients. A total of 302 consecutive renal transplant recipients were enrolled in this prospective study. Peripheral blood lymphocyte subsets were quantified and analyzed with respect to other known cardiovascular risk factors. The patients were followed for a mean duration of 23.5 +/- 4.5 mo. Mean CD4, CD8, and CD19 cell levels were 511 +/- 290/mm(3), 553 +/- 596/mm(3), and 66 +/- 62/mm(3), respectively. CD4 levels were positively related to transplant duration (r = 0.32; P = 0.02) and inversely related to age (r = 0.35; P = 0.01). Twenty-five atherosclerotic events (AE) occurred in 25 patients (8.3%). CD4 levels were lower in patients who experienced CVE (288 +/- 170/mm(3) versus 531 +/- 290/mm(3); P < 0.0001). Cox regression analysis showed that patients in the three upper quartiles of CD4 cell count had a decreased risk of CVE compared with those in the lowest quartile. There was a linear increase in risk of CVE with decreasing CD4 cell count (P < 0.0001). A CD4 cell count in the highest quartile (>663/mm(3)) divided the risk of CVE by 10 as compared with the lowest quartile. In conclusion, CD4 lymphocytopenia is an independent risk factor for the development of cardiovascular complications in renal transplant recipients, suggesting that impaired immune response promotes accelerated atherogenesis in this population.

Adult↗
PubMed2003

[Tolerance in transplantation: potential contribution of haematopoietic transplantation and cell therapy].

The ultimate objective of organ transplantation is to obtain a state of tolerance, i.e. long-term acceptance of the graft without immunosuppressive therapy in order to limit the complications of these treatments (viral infections, tumours, etc.). The various immunological mechanisms allowing a state of tolerance will be described in this review. Among these various experimental strategies, combined bone marrow (or haematopoietic stem cell) transplantation and organ transplantation, made possible by the development of non-myeloablative or less intensive conditioning, appears to be one of the most promising lines of research. This approach leads to colonization of the recipient by donor cells. This state is described as "macro-chimerism" and achieves a real state of central tolerance in relation to an organ derived from the bone marrow donor. We have shown recently that intravenous injection of apoptotic cells in combination with allogeneic bone marrow cells increases the success rate of bone marrow transplantation. In a model of combined bone marrow/solid organ transplantation, these apoptotic cells induce tolerance limited to the donor's bone marrow cell antigens without inducing auto-immunization. We therefore propose a new approach to cell-based therapy (using the immunomodulating properties of apoptotic cells) to promote the success of haematopoietic stem cell transplantation. This approach can be particularly useful in combined haematopoietic stem cell and organ transplantation in order to induce a state of macro-chimerism.

Animals↗
PubMed2002

Flow cytometric evaluation of pregnancy-induced anti-HLA immunization and blood transfusion-induced reactivation.

BACKGROUND: Pregnancy-induced alloimmunization (PIA) may decrease to a level that becomes undetectable by complement-dependent cytotoxicity (CDC). Nevertheless, such alloimmunization may provoke acute rejections after kidney transplantation and lead to broad-spectrum immunizations after transfusion. Flow-cytometry (FC) was used to estimate the frequency of low-level PIA and to evaluate its influence on posttransfusion alloimmunization profiles. METHODS: To evaluate the frequency of low-level PIA, the sera of 36 women, free of CDC-detectable anti-HLA IgG (CDC-IgG- negative), were cross-matched by FC against their husband's or offspring's lymphocytes and further analyzed with human leukocyte antigen (HLA) Ag-coated microbeads (Flow-PRA One-Lambda, Canoga Park, CA). To evaluate the influence of low-level alloimmunization on posttransfusion appearance of CDC-IgG, pretransfusion sera of a second cohort of 43 women, also CDC-IgG-negative and included in a transfusion protocol, were analyzed by Flow-PRA. Posttransfusion sera were analyzed for the development of cytotoxic IgG. RESULTS: Ten of the first cohort of 36 (27.8%) CDC-IgG-negative women showed a positive FC cross-match against the husband or offspring lymphocytes. Flow-PRA analysis confirmed that 9 of 10 positive cross-matched sera contained anti-HLA IgG. Among the 43 transfused patients, 11 of 16 (68.7%) of the women who were CDC-IgG-positive after blood transfusion showed FC-detectable IgG before transfusion; although 2 of 27 (7.4%) of the patients who remained CDC-IgG-negative after transfusion showed FC-detectable IgG before transfusion (P <0.001). CONCLUSION: Most of the de novo anti-HLA immunizations detected by CDC after transfusion in previously pregnant women can be detected by Flow-PRA before transfusion.

Blood Transfusion↗
PubMed2002

Lymphocyte subsets and assessment of cancer risk in renal transplant recipients.

Renal transplant recipients have a well-recognized increased risk of de novo neoplasia. In this study, we investigated whether lymphocyte subset count could predict the risk of developing noncutaneous neoplasia (NCSC) in renal transplant recipients (RTR). Between January 1995 and December 1995, lymphocyte subsets (CD4, CD8, CD19) were measured in 281 RTR. This population was studied until November 1999 for the development of NCSC. The mean follow-up was 42+/-9 months. Neoplasm was diagnosed in 22 patients (7.9%). Patients who developed a cancer were significantly older (53.8+/-6 years vs 38+/-16 years, P<0.0001), had lower CD4 (234+/-126/mm(3) vs 543+/-214/mm(3), P<0.005) and CD19 (19+/-9/mm(3) vs 51+/-22/mm(3), P<0.0001) levels, and more frequently had past histories of skin cancer (24% vs 4%, P<0.01). Cox regression revealed that high CD4 levels (RR 0.73, 95% CI 0.62-0.89 for each 100/mm(3) increase in CD4 cell count) were associated with decreased risk of NCSC, whereas age (RR 2.49, 95% CI 1.12-5.92 for each 10-year increase in age) was predictive of the subsequent development of NCSC. To conclude, CD4 cell depletion is associated with the development of solid cancers and lymphoma in RTR.

Adult↗
PubMed2002

Increased presence of anti-HLA antibodies early after allogeneic granulocyte colony-stimulating factor-mobilized peripheral blood hematopoietic stem cell transplantation compared with bone marrow transplantation.

We have recently shown that the use of allogeneic granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood hematopoietic stem cell transplantation (PBHSCT), as compared with bone marrow transplantation (BMT), is associated with increased titers of antibodies (Abs) directed against red blood cell ABO antigens. To further evaluate the influence of a G-CSF-mobilized PBHSCT graft on alloimmune Ab responses, we examined the frequency of anti-HLA Abs after transplantation in the setting of the same randomized study, comparing PBHSCT with BMT in adults. Anti-HLA Ab presence was determined by complement-dependent cytotoxicity assay (CDC) and flow cytometry in the recipient before and 30 days after transplantation as well as in the donor before graft donation. The use of PBHSCT was significantly associated with increased detection of anti-HLA immunoglobulin G (IgG) Abs early after transplantation as evidenced by flow cytometry (11 of 24 versus 4 of 27 transplant recipients, P =.03) and, less so, by CDC (5 of 24 versus 1 of 27 transplant recipients, P =.09). The difference between PBHSCT and BMT was further heightened when analysis was restricted to anti-HLA IgG Ab-negative donor/recipient pairs. In such a setting, early anti-HLA Ab was never detected after BMT but was repeatedly detected after PBHSCT (flow cytometry, 6 of 18 versus 0 of 17 transplant recipients, P =.02; CDC, 4 of 23 versus 0 of 26 transplant recipients, P =.04). Importantly, the PBHSCT-associated increase in anti-HLA Ab detection was observed despite a reduction in the median number of platelet-transfusion episodes per patient in PBHSC transplant versus BM transplant recipients (3 platelet-transfusion episodes [range, 1-21] in PBHSCT group vs 6 platelet-transfusion episodes [range, 3-33] in the BMT group; P =.02). In conclusion, this study strongly suggests that G-CSF-mobilized PBHSCT results in an increased incidence of circulating anti-HLA Abs and further confirms that the use of such a graft alters alloimmune Ab responses.

Adult↗