Biomedical subjects

M Kuentz

Publications and source records attributed to M Kuentz.

At least 37 records · Page 2Linked to original sources

PubMed2001

Autologous reconstitution combined with durable leukemic remission after allogeneic BMT for CML: absence of persistence of a donor-derived T cell effector population.

We report a case of autologous hematopoietic recovery with durable leukemic remission after BMT from a phenotypically HLA-identical donor in a 30-year-old male with CML. Graft loss was diagnosed from day 60 post-BMT by VNTR PCR. To assess for the presence of a minor donor-derived T cell population that could exert an anti-leukemic effect, we serially applied a sensitive process of chimerism analysis by fluorescent PCR on sorted T cells. No residual donor T cells could be detected. We also showed retrospectively that a very sensitive method of MRD analysis by real-time quantitative PCR could have permitted prediction of relapse in this case.

Adult↗

PubMed2001

Genotypically nonidentical related donors for transplantation of patients with myelodysplastic syndromes: comparison with unrelated donor transplantation and autologous stem cell transplantation.

Transplantation with histocompatible identical siblings is a curative treatment for patients with myelodysplastic syndromes (MDS). Alternative treatments, such as transplantation with other family donors, are an option for patients without HLA-identical siblings. This study evaluated transplantation with genotypically nonidentical family donors and compared the results to those obtained with unrelated donors and autologous stem cell transplantation. Overall 3-year survival was 35% for the 79 patients transplanted using genotypically nonidentical donors, DFS was 31%, relapse risk 16%, and the treatment-related mortality (TRM) 62%. Patients transplanted using phenotypically identical family donors had a significantly superior survival and a lower TRM than patients transplanted with mismatched family donors. Age had no influence on the outcome of transplantation. The DFS of patients transplanted in early stage of the disease was 42% compared to 28% in patients transplanted with more advanced disease (P = 0.03). The results of transplantation with mismatched family donors were comparable to those obtained with unrelated donor transplantation. This suggests that nonidentical family donors may be considered if a fully matched unrelated donor is not available. The TRM of patients transplanted with nonidentical family donors is significantly higher than the TRM of patients transplanted with autologous stem cells. The disease-free survival of ASCT is not inferior to allogeneic transplantation using nonidentical family donors, and the intensity of the treatment is much lower. The choice of ASCT or alternative donor transplantation must be influenced by the age of the patient and the risk of relapse. For patients under the age of 20 years the treatment of choice may indeed be an alternative donor transplantation.

Adolescent↗

PubMed2001

Enhanced activation of B cells in a granulocyte colony-stimulating factor-mobilized peripheral blood stem cell graft.

In a randomized study that compared human leucocyte antigen-identical allogeneic granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell (PBSC) versus bone marrow (BM) transplantation, the expression of activation markers, CD23, CD25 and CD45RO by B cells, was compared in blood before and after G-CSF mobilization and in PBSC versus BM grafts. The fractions of CD23+ and CD25+ B cells were higher in PBSC than in BM grafts. Moreover, we observed a G-CSF-induced increase in B-cell fractions in blood as well as in PBSC grafts when compared with BM grafts. Such an enhanced B-cell activation could contribute to the accelerated kinetics of immuno-haematological reconstitution, the occurrence of acute haemolysis in the ABO minor incompatibility setting, as well as the increased incidence of chronic graft-versus-host disease observed after PBSC transplantation.

B-Lymphocytes↗

PubMed2000

A new theoretical approach to tablet strength of a binary mixture consisting of a well and a poorly compactable substance.

The objective of this study was to analyse the tensile strength of a well and a poorly compactable substance in a tablet mixture. Recent developments in the theory of percolation were taken into account and two power laws are proposed, one for the tensile strength as a function of the relative density of the mixture, and the other for the relationship between the strength and compaction pressure. Both equations are assumed to be valid in a comparatively low pressure range. A universal testing instrument Zwick UPM 1478 was used for the manufacture and testing of the compacts. Mixtures of Avicel PH101 and paracetamol at different ratios were chosen as model systems. The experimental results showed that the proposed model equations fitted the experimental data reasonably well for all mixture ratios. It was observed that the critical solid fraction of the mixture, i.e. the strength percolation threshold, increased with rising amounts of the drug. We investigated the strength threshold not only in terms of the solid fraction, but also in terms of the mass fraction (excipient percolation threshold). It is assumed that a tablet can only be produced with a certain minimal amount of the well compactable substance that is needed to build a percolating cluster in the tablet. An interpretation is therefore provided for the dilution capacity of a direct tableting excipient with a poorly compactable drug. The dilution capacity was experimentally determined according to the method of Minchom and Armstrong (Br. Pharm. Conf. (1987) 69 pp.). Our experimental estimate of 79.9% drug is in perfect agreement with our proposed theoretical calculation of 79.7%. These estimates are, however, much higher than the one reported in a recent study (Y. Habib, L. Augsburger, G. Reier, Th. Wheatley, R. Shangraw, Dilution potential: a new perspective, Pharm. Dev. Tech. 1 (2) (1996) 205-212) where the dilution capacity of the same mixture was investigated. This discrepancy can be explained based on the different pressure ranges and extrapolation techniques that were used. As a conclusion, concepts of the percolation theory can successfully be applied to the kind of mixture studied in this paper. It is conceivable that the theoretical tools presented can also be applied to mixtures of more than two substances if they consist of a single well compactable excipient and several poorly compactable components. Such mixtures are relevant for the development of direct compressible tableting formulations.

Pressure↗

PubMed2000

Allogeneic peripheral blood hematopoietic stem cell transplantation: guidelines for red blood cell immuno-hematological assessment and transfusion practice.Société Française de Greffe de Moelle.

Allogeneic peripheral blood hematopoietic stem cell transplantation (PBSCT) is presently being evaluated in a French randomized study comparing peripheral blood vs bone marrow. Cases of potentially lethal acute hemolysis have recently been reported after allogeneic PBSCT in the presence of a 'minor' ABO incompatibility. Patients were frequently transfused with recipient-compatible and donor-incompatible RBC and usually did not receive methotrexate in addition to cyclosporin A for graft-versus-host disease (GVHD) prophylaxis. In order to homogenize immuno-hematological (IH) assessment and transfusion practices within our protocol, we made proposals to 25 allo-transplant French centers on the following aspects: pre-inclusion IH assessment, IH exclusion criteria, transfusion rules, post-transplant IH surveillance and treatment of hemolysis. Analysis of responses to our proposals led to the elaboration of guidelines which were approved and implemented by the French Bone Marrow Transplantation Society (SFGM). Pre-inclusion IH testing includes mandatory detection and titration of anti-RBC allo-Ab, as well as titration of anti-A and anti-B Ab. The presence in the donor of an anti-A (group A or AB recipients), anti-B (group B or AB recipients) Ab with a titer >1/32 or the presence of allo-Ab against Rh, Kell, Fya, Fyb, Jka, Jkb, Ss Ag present on recipient RBC is an exclusion criterion for the protocol. ABO and RhD compatibility of RBC blood products with both HSC donor and recipient is mandatory. A similar compatibility is also required for Rh (other than D) and Kell Ag. If not possible, compatibility of RBC blood products with the HSC donor is mandatory. Lastly, guidelines regarding post-transplantation IH follow-up as well as acute hemolysis treatment have been elaborated. The implementation of these guidelines should contribute to enhancing the quality of transfusion practice after PBSCT. Such an approach will be applied to other aspects of transfusion medicine in the setting of HSC transplantation. Bone Marrow Transplantation(2000) 25, 507-512.

Blood Grouping and Crossmatching↗

PubMed2000

Radiation-induced bone sarcoma following total body irradiation: role of additional radiation on localized areas.

A 44-year-old patient who had had acute monoblastic leukemia developed an osteosarcoma of the pelvic bones 5 years after an allogeneic bone marrow transplant from his HLA-identical sister. He had additionally received superficial cutaneous radiation of the legs and pelvis, over the 3 weeks prior to total body irradiation (TBI), because of cutaneous leukemic lesions. The tumor was a fibrohistiocytomatous osteogenic sarcoma. The first lesion was in the right ilium, and a second lesion appeared 18 months later, symmetrically on the left ilium. Despite treatment, the patient died from metastases. At the time of diagnosis of radiation-induced sarcoma, the patient was free of leukemia and had several risk factors already reported to favor the development of solid tumors in stem cell recipients. These include acute leukemia, TBI and graft-versus-host disease. As he developed symmetrical lesions of the pelvic bone, and because of the histology of the radiation-induced tumor, we assumed that the additional radiation of the skin prior to TBI may have contributed to the pathogenesis of this malignant fibrous histiocytoma. Therefore, the risk/benefit ratio should be carefully considered in unusual indications. These patients should benefit from a close follow-up of the superimposed areas.

Adult↗

PubMed2000

Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Société Française de Greffe de Moelle (SFGM).

To assess the place of allogeneic hematopoietic stem cell transplantation (HSCT) in the advanced stage of acute myeloid leukemia (AML), we retrospectively analyzed 379 consecutive patients who underwent allogeneic HSCT for advanced AML. The median follow-up of the entire cohort was 7.5 years. Sixty-nine patients (18%) were transplanted with primary resistant disease. Three hundred and ten (82%) were relapsed patients, 94 (30%) of whom were in untreated relapse, 67 (22%) in refractory relapse and 149 (48%) in 2nd or 3rd complete remission at time of transplantation. The 5-year probabilities of overall survival (OS), disease-free survival (DFS), and transplant-related mortality (TRM) were 22 +/- 4%, 20 +/- 4%, 45 +/- 6%, respectively. In multivariate analysis, we demonstrated the favorable impact on OS, DFS and TRM of two factors over which we have no control (age <15 years, complete remission achievement) and three factors over which we have some control (female donor, acute and chronic graft-versus-host disease). The results of this study suggest that the graft-versus-leukemia effect is important in advanced AML and that new HSCT modalities are needed for some patients with this indication.

Acute Disease↗

PubMed2000

Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Société Française de Greffe de moelle (SFGM).

Although recurrent malignancy is the most frequent indication for second stem cell transplantation (2nd SCT), there are few reports that include sufficiently large numbers of patients to enable prognostic factor analysis. This retrospective study includes 150 patients who underwent a 2nd SCT for relapsed acute myeloblastic leukaemia (n = 61), acute lymphoblastic leukaemia (n = 47) or chronic myeloid leukaemia (n = 42) after a first allogeneic transplant (including 26 T-cell-depleted). The median interval between the first transplant and relapse, and between relapse and second transplant was 17 months and 5 months respectively. After the 2nd SCT, engraftment occurred in 93% of cases, 32% of patients developed acute graft-vs.-host disease (GVHD) >/= grade II and 38% chronic GVHD. The 5-year overall and disease-free survival were 32 +/- 8% and 30 +/- 8%, respectively, with a risk of relapse of 44 +/- 12% and a transplant-related mortality of 45 +/- 9%. In a multivariate analysis, five factors were associated with a better outcome after 2nd SCT: age < 16 years at second transplant; relapse occurring more than 12 months after the first transplant; transplantation from a female donor; absence of acute GVHD; and the occurrence of chronic GVHD. The best candidates for a second transplant are likely to be patients with acute leukaemia in remission before transplant, in whom the HLA-identical donor was female and who relapsed more than 1 year after the first transplant.

Acute Disease↗

PubMed2000

Second early allogeneic stem cell transplantations for graft failure in acute leukaemia, chronic myeloid leukaemia and aplastic anaemia. French Society of Bone Marrow Transplantation.

In this retrospective multicentre study, we analysed the results of 82 consecutive second early allogeneic transplants for primary (n = 28) or secondary ([n = 54) graft failures performed between 1985 and 1997 in patients with acute leukaemia (n = 33), aplastic anaemia (n = 29) or chronic myeloid leukaemia (n = 20). HLA-matched siblings were used in 64 cases. The same donors were used for both transplants in 56 cases and the first transplant was T-cell depleted in 30 cases. The median age at transplant was 25 years and the median intertransplant time interval was 2 months. Estimates of the 3-year overall survival and day 100 transplant-related mortality were 30% and 53% respectively. A recipient age < 34 years at transplant, an intertransplant time interval > or = 80 d and a positive recipient cytomegalovirus serology were predictors of a better outcome. The use of cyclosporin A (CsA) after second transplant had a dramatic impact on outcome, the best results being observed with CsA alone. The day 40 probability of neutrophil recovery was 73%. The use of peripheral blood progenitor cells (PBPCs) was associated with a higher and faster neutrophil recovery. Other factors associated with neutrophil recovery were an intertransplant time interval > or = 80 d and a positive recipient cytomegalovirus serology. Therefore, second early allogeneic transplantation for graft failure is an effective treatment, especially if patients can receive CsA for graft-versus-host disease prevention and are retransplanted more than 80 d from first transplant.

Adolescent↗

PubMed2000

Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Société Française de Greffe de Moelle.

PURPOSE: To compare hematologic recovery in patients receiving allogeneic blood cell transplantation (BCT) with those receiving allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: One hundred eleven patients with leukemia in the early stages and with HLA-matched sibling donors were randomized in this study. One hundred one underwent transplantation. Standard procedures for collection and transplantation were used. Patients did not receive prophylactic granulocyte colony-stimulating factor after undergoing transplantation. In addition to clinical end points being established, a prospective and comparative economic evaluation of the first 6 months after transplantation was performed. RESULTS: Groups were balanced for patient, donor, and transplant characteristics. Blood cell collection led to the collection of a higher number of CD34(+) and CD3(+) cells than did bone marrow collection (P < 10(-6)) without reported side effects for the donor. Patients in the BCT group reached platelet counts of 25 and 50 x 10(9) platelets/L 8 and 11 days earlier than did the BMT group (P < 10(-4) and P < 10(-5)), respectively. This resulted in fewer platelet transfusions during the first 180 days after transplantation (P =.002) for the former group. The time to reach neutrophil counts of 0.5 and 1 x 10(9) neutrophils/L was 6 and 7 days shorter, respectively, in the BCT group than in the BMT group (P < 10(-5)). This quicker hematologic recovery was associated with a shorter length of hospitalization and a decrease in total cost of procedure during the first 6 months. CONCLUSION: This study establishes that allogeneic BCT results in quicker hematologic recovery but is associated with a higher occurrence of chronic graft-versus-host disease.

Acute Disease↗

PubMed2000

Allogeneic bone marrow transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia: a long-term study of 70 patients-report of the French society of bone marrow transplantation.

PURPOSE: To identify predictive factors of survival, relapse, and transplantation-related mortality (TRM) among patients with therapy-related myelodysplastic syndrome (t-MDS) or acute leukemia (t-AML) who underwent allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: From 1980 to 1998, 70 patients underwent allogeneic BMT for t-MDS (n = 31) or t-AML (n = 39) after prior cytotoxic exposure. Thirty-three patients had received induction-type chemotherapy before BMT. At the time of transplantation, there were 24 patients in complete remission (CR) and 46 with active disease. RESULTS: With a median follow-up of 7.9 years (range, 1.1 to 18.8 years) after BMT, 16 patients are alive, whereas 19 died of relapse, 34 of TRM, and one of relapse of the primary disease. The estimated 2-year overall survival, event-free survival, relapse, and TRM rates were 30% (95% confidence interval [CI], 19% to 40%), 28% (95% CI, 18% to 39%), 42% (95% CI, 26% to 57%), and 49% (95% CI, 36% to 62%), respectively. In multivariable analysis, age greater than 37 years, male sex, positive recipient cytomegalovirus (CMV) serology, absence of CR at BMT, and intensive schedules used for conditioning were associated with poor outcome. CONCLUSION: BMT is an effective treatment for patients with t-MDS or t-AML who have responsive disease and, in particular, who have no poor-risk cytogenetic features. The poor results of the other patients, especially those with active disease at BMT, emphasize the need to delineate indications and perform prospective protocols.

Adolescent↗

PubMed1999

Fracture in disordered media and tensile strength of microcrystalline cellulose tablets at low relative densities.

The purpose of this study is to establish a theoretical basis for the tensile strength of low density tablets. In a first step, a lattice model based on percolation theory is presented. As a theoretical result, a power law is obtained for the lattice strength. The exponent in this law is expected to be universal and as a numerical value Tf congruent with 2.7 is proposed. The result is identical with an earlier theoretical finding from an alternative approach proposed by. In a second step, the new model equation is applied to the tensile strength of low density tablets. The compacts were manufactured and tested with an universal testing instrument Zwick UPM 1478 (Zwick-Roell). Different types of microcrystalline cellulose Emcocel 50M, Emcocel 90M, Avicel PH101 and Avicel PH102 were assayed as model excipients because of their ability to form tablets at comparatively low relative densities (rhor). For determination of the tensile strength, two different strain rates 0.5 and 25 mm min-1 were examined. All experimentally determined exponents were in the same range with an average of Tf=3.2+/-0.1 and the critical solid fractions (rhorc), yielded values close the relative bulk densities. In a third step, the new model is compared to the Ryshkewitch-Duckworth equation. This exponential relationship of the tensile strength and porosity was found to have an inferior fitting adequacy than the new power law. As a conclusion, the lattice model presented is able to explain the power law behaviour of the tensile strength as a function of the relative density with an exponent close to three. The expected universal character of this exponent was supported by the results of the assayed substances at two different strain rates. Plus, in the case of the tested substances, the new relationship between the tensile strength and the relative density should be preferred to the often used exponential function. However, further studies have to be conducted to know more about the validity of the new model.

Cellulose↗

PubMed1999

[Erythrocyte transfusion practices after allogeneic hematopoietic stem cell transplantation].

Allogeneic peripheral blood hematopoietic stem cell transplantation is being evaluated in a randomized French study comparing the use of peripheral blood stem cells vs. bone marrow graft stem cells. In order to standardize immunohematological (IH) assessment and transfusion practices within our protocol, we made suggestions to 25 allo-transplantation French centers on the following elements: pre-inclusion IH assessment, IH exclusion criteria, transfusion rules, post-transplantation IH surveillance and treatment of hemolysis. The analysis of their responses to our suggestions led us to elaborate recommendations which were approved and implemented by the French Bone Marrow Transplantation Society (SFGM). These recommendations concern the transfusion practice in the general framework of allogeneic hematopoietic stem cell transplantation and can therefore be considered as referential.

Contraindications↗

PubMed1999

Pressure susceptibility of polymer tablets as a critical property: a modified Heckel equation.

The pressure susceptibility (chip), which is defined as the decrease of porosity (epsilon) under pressure was investigated. Of special interest are compacts obtained at very low pressures, because of the transition between the state of a powder and the state of a tablet. This range was found to be critical in respect to a diverging pressure susceptibility. Above a critical porosity (epsilonc) or below the corresponding relative density (rhoc), no pressure susceptibility can be defined, because of no rigid structure exists. To take this into account, a simple function was proposed for the pressure susceptibility: chip approximately 1/(epsilonc - epsilon). This proposal leads to a new porosity vs pressure relationship. The new model was compared to the Heckel equation that involves a constant pressure susceptibility. Various polymers were tested from "out of die" measurements, and the new relationship was found superior to the Heckel equation. As a conclusion, the pressure susceptibility exhibits a curvature that can be called critical at low relative densities. Consequently, a better understanding evolves as to why the Heckel equation is not valid at low pressures. The new model has proven to be adequate for polymer tablets but, so far it is not clear whether other substances exhibit the same performance. Especially tableting materials exhibiting brittle fracture will be of interest considering their importance in compaction technology.

Excipients↗

PubMed1999

Allogeneic bone marrow transplantation in aggressive non-Hodgkin's lymphoma (excluding Burkitt and lymphoblastic lymphoma): a series of 73 patients from the SFGM database. Sociét Française de Greffe de Moelle.

The place of allogeneic bone marrow transplantation (BMT) in the treatment of aggressive non-Hodgkin's lymphoma (NHL) remains controversial. We conducted a retrospective study of French experience in allografting NHL between 1984 and 1994. To improve the homogeneity of the study population, cases of low-grade, Burkitt and lymphoblastic NHL were excluded. 73 patients were included in the analysis. Median age at transplantation was 35 years (range 9-61 years); 64 patients were in stage IV and 45 had bone marrow involvement at diagnosis. At the time of transplantation, 46 patients had sensitive disease (25 in complete remission; CR). The overall survival (OS) and progression-free survival (PFS) rates were 41% and 40% respectively at 5 years (median follow-up of survivors 90 months). The probability of disease progression was 30% at 5 years, and only one relapse occurred after 15 months. 32 patients died of transplantation-related complications. In multivariate analysis, pretransplant complete remission was the main factor associated with longer survival (OS at 60 months of 76% among the 25 patients in CR at transplant and of 23% among the 48 patients not in CR at transplant). Neither acute nor chronic graft-versus-host disease (GvHD) influenced the relapse rate. In conclusion, in this high-risk population the overall results of allogeneic BMT were encouraging, despite a high transplant-related mortality rate. We believe this procedure should be studied further in prospective controlled trials.

Adolescent↗

PubMed1999

Comparison of high-dose therapy and autologous stem-cell transplantation with conventional therapy for Hodgkin's disease induction failure: a case-control study. Société Francaise de Greffe de Moelle.

PURPOSE: To determine the prognostic factors and outcome of first-line induction failure Hodgkin's disease patients who were treated with a salvage regimen of high-dose chemotherapy and autologous stem-cell transplantation, and to compare them with matched, conventionally treated patients. PATIENTS AND METHODS: We retrospectively analyzed data relating to 86 Hodgkin's disease patients who underwent autologous stem-cell transplantation after failure of the first chemotherapy regimen, either because they did not enter a complete remission and experienced progression of disease less than 3 months after the end of their first-line treatment or because they showed evidence of disease progression during first-line therapy. Graft patients were matched with 258 conventionally treated patients (three controls per case) for age, sex, clinical stage, B symptoms, and time at risk; patient data were obtained from international databases. RESULTS: Among the 86 graft patients, the median age at diagnosis was 29 years (range, 14 to 57 years). Thirty-nine percent of patients had stage II disease, 23% had stage III disease, and 38% had stage IV disease. Seventy percent of the patients received chemotherapy and 30% received combined modality therapy; 60% of the patients received a seven- or eight-drug regimen. After this first-line treatment, 91% had disease progression and 9% had a brief partial response. Eighty patients received a second-line treatment; pretransplantation status was as follows: 24% of patients had a complete remission, 38% had a partial remission (PR), 14% had stable disease, and disease progression occurred in 24%. With a median follow-up of 22 months (range, 4 to 105 months) from diagnosis, the 5-year event-free survival and overall survival rates from transplantation were 25% and 35% (95% confidence intervals, 15 to 36 and 23 to 49), respectively. In multivariate analysis, the pretransplantation disease status after salvage therapy was the only significant prognostic factor for survival (PR: relative risk = 2.8, P = .017; progressive disease: relative risk (RR) = 5.26, P < .001). From diagnosis, the 6-year overall survival rates of the graft patients and 258 matched conventionally treated patients were 38% and 29%, respectively (P = .058). CONCLUSION: Autologous stem-cell transplantation represents the best therapeutic option currently available for patients with primary induction failure and is associated with acceptable toxicity. Response to second-line treatment before high-dose chemotherapy is the only prognostic factor that can be correlated with survival.

Adolescent↗

PubMed1999

Poor lymphocyte recovery following CD34-selected autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

Positive selection of CD34+ cells in autologous grafts, designed to deplete tumour cells, also results in T-cell depletion. To assess the reconstitution of the different lymphocyte subsets and of the T-cell repertoire diversity following autologous transplantation of selected CD34+ peripheral blood stem cells (PBSC), we analysed sequential blood samples in eight patients autografted for advanced B-cell non-Hodgkin's lymphoma in a phase I-II pilot study. Although natural killer cell recovery was rapid, T- and B-cell recovery was delayed with a median of 110/microliters CD4+, 175/microliters CD8+ T cells and 45/microliters B cells at 12 months post-transplant. The naive CD45RA+ T-cell compartment was profoundly deficient up to 12 months for both CD4+ and CD8+ subsets. A transient expansion of memory CD8+CD45RO+ T cells consisting of an increased percentage of CD57+CD28- cells occurred within the first 3 months post-transplant, but the memory CD4+CD45RO+ T cells remained far below the normal value. The CD8+CD28+ T-cell subset did not recover. Using multiplex PCR analysis of the T-cell receptor gamma locus, we found that the repertoire diversity improved at 12 months after being poor and oligoclonal during the first 3 months post-transplant. As shown by monoplex PCRgamma analysis of every VJ combination, despite T-cell depletion of the graft, mature T cells were carried over with the selected CD34+ PBSC and contributed to the T-cell recovery after transplantation.

Antigens, CD34↗

PubMed1998

Reverse seroconversion of hepatitis B after allogeneic bone marrow transplantation: a retrospective study of 37 patients with pretransplant anti-HBs and anti-HBc.

BACKGROUND: Reverse seroconversion to hepatitis B virus (HBV), i.e., HBV reactivation in patients with pretransplant antibodies to hepatitis B surface antigen (anti-HBs) and to hepatitis B core antigen (anti-HBc), is rarely re-ported after allogeneic bone marrow transplantation. METHODS: To determine this risk, we studied clinical outcome and serological changes in 37 patients with pretransplant anti-HBs and anti-HBc. RESULTS: In 33 cases, no change in HBV markers was observed in the posttransplant period. In four cases, anti-HBs and anti-HBc were lost, and hepatitis B surface antigen, hepatitis B e antigen, and HBV DNA emerged together with acute hepatitis, after cessation of immunosuppression. The actuarial risk of reactivation in the 37 patients was 20.5% (median follow-up 20 months). No reactivation occurred in patients with anti-HBs-positive donors. CONCLUSION: Although few cases of postallogeneic bone marrow transplantation reverse seroconversion to HBV have been reported, this study demonstrates that the actuarial risk is relatively high and suggests that donor vaccination might be proposed prophylactically or that HBs-specific immunoglobulin infusions might be warranted.

Adolescent↗