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M Kuentz

Publications and source records attributed to M Kuentz.

At least 19 recordsLinked to original sources
PubMed2001

Allogeneic hematopoietic stem-cell transplantation after nonmyeloablative preparative regimens: impact of pretransplantation and posttransplantation factors on outcome.

PURPOSE: To analyze the impact of pre- and posttransplantation factors on the outcome of allogeneic transplantation after nonmyeloablative conditioning regimens. PATIENTS AND METHODS: Ninety-two allogeneic transplantations after nonmyeloablative preparative regimens were reported to the Société Française de Greffe de Moelle Registry registry. Initial diagnoses were lymphoid diseases (n = 22), myeloma (n = 14), acute leukemia and myelodysplasia (n = 41), chronic myelogenous leukemia (n = 12), and solid tumors (n = 3). Forty-six patients had previously received a transplant, and 49 had progressive disease before transplantation. Three types of conditioning regimens were used with fludarabine or antithymocyte globulins. Eighty-nine patients underwent transplantation, 60 from peripheral-blood progenitor cells. Eighty-six patients received graft-versus-host disease (GHVD) prophylaxis for a median duration of 53 days. RESULTS: Seventy-nine patients engrafted, with 40 complete and 21 mixed chimerisms. The acute GHVD rate at 3 months was 50% +/- 11%. Fifty-two patients achieved complete remission and 12, partial remission. At 18 months after transplantation, the overall survival (OS) and the transplant-related mortality (TRM) were 32% +/- 12% and 38% +/- 14%, respectively. Initial diagnosis and disease status before transplantation significantly influenced survival. Age and GHVD prophylaxis type significantly influenced TRM. We also showed an impact of GHVD prophylaxis duration on OS and TRM. In multivariate analysis, three factors remained of prognostic value on OS: initial diagnosis, disease status at transplantation, and GHVD prophylaxis duration. CONCLUSION: This series shows encouraging results from nonmyeloablative conditioning regimens before allotransplantation and demonstrates the impact of some pre- and posttransplantation factors on outcome after transplantation.

Adolescent↗
PubMed2001

Influence of the hematopoietic stem cell source on early immunohematologic reconstitution after allogeneic transplantation.

Several acute hemolysis episodes, sometimes lethal, have been recently described after transplantation of allogeneic peripheral blood hematopoietic stem cells (PBHSCs). Hemolysis resulted from the production of donor-derived antibodies (Abs) directed at ABO antigens (Ags) present on recipient red blood cells (RBCs). A multicenter randomized phase III clinical study comparing allogeneic PBHSC transplantation (PBHSCT) versus bone marrow hematopoietic stem cell transplantation (BMHSCT) has been conducted in France. In the course of this study, serum anti-A and/or anti-B Ab titers were compared before the conditioning regimen and on day +30 after transplantation in 49 consecutive evaluable PBHSCT (n = 21) or BMHSCT (n = 28) recipients. PBHSCT resulted in a higher frequency of increased anti-A and/or anti-B Ab titers 30 days after transplantation as compared to BMHSCT: 8 (38%) of 21 versus 3 (11%) of 28 (P =.04). In PBHSCT recipients, increased titers were observed mostly after receiving a minor ABO mismatch transplant: 5 of 7 versus 3 of 14 in the absence of any minor ABO mismatch (P =.05), whereas this was not the case after BMHSCT: 1 of 8 versus 2 of 20. Anti-A and/or anti-B serum Abs detectable at day +30 after PBHSCT were always directed against A and/or B Ags absent both on donor and recipient RBCs. Finally, 3 of 21 PBHSCT versus 0 of 28 BMHSCT recipients developed anti-allogeneic RBC Abs other than ABO (P =.07). Overall, the data strongly suggest that immunohematologic reconstitution differs significantly after granulocyte colony-stimulating factor-mobilized PBHSCT when compared to BMHSCT. Such a difference could contribute to the acute hemolysis described after PBHSCT as well as to distinct alloreactivity after PBHSCT.

Adolescent↗
PubMed2001

Chimerism analysis by lineage-specific fluorescent polymerase chain reaction in secondary graft failure after allogeneic stem cell transplantation.

BACKGROUND: Chimerism analysis is essential in understanding the etiology of graft failure occurring after allogeneic stem cell transplantation. The detection of marrow and/or blood host cells suggests graft rejection, relapse of the underlying disease, or a state of stable mixed chimerism. However, complete donor chimerism may be observed in some cases. Our objective was to characterize, by a sensitive process of chimerism analysis, six cases of graft failure occurring after transplant. METHODS: Six cases of secondary graft failure, in which previous analysis had shown complete donor chimerism by standard polymerase chain reaction amplification of variable number of tandem repeats, were studied. In order to detect a minority population of recipient cells, we increased the sensitivity of the process by using fluorescent polymerase chain reaction and analyzing the origin of T, B, and natural killer lymphocytes at the time of graft failure. RESULTS: The complete donor origin of mononuclear cells and lymphocytic populations was confirmed with this method in five of six patients. In the remaining patient, diagnosis of graft failure was clarified by the detection of a previously undetected mixed chimerism, compatible with graft rejection. In the other five patients, graft rejection was thereby excluded and graft failure could be related to viral infection or to graft-versus-host disease. CONCLUSION: Our sensitive process of fluorescent lineage-specific chimerism analysis may help in distinguishing between graft rejection and other mechanisms of graft failure, which is essential for deciding appropriate therapy.

Adolescent↗
PubMed2001

Effect of granulocyte colony-stimulating factor mobilization on phenotypical and functional properties of immune cells.

Some phenotypic and functional properties of lymphocytes from bone marrow or peripheral blood stem cell donors were compared in a randomized study. Lymphocyte subsets were analyzed by immunocytometry in blood harvested from bone marrow donors (n = 27) and from peripheral blood stem cell donors before and after granulocyte colony-stimulating factor mobilization (n = 23) and in bone marrow and peripheral blood stem cell grafts. Granulocyte colony-stimulating factor mobilization increased the blood T and B, but not NK, lymphocyte counts. All lymphocyte counts were approximately 10-fold higher in peripheral blood stem cell grafts than in bone marrow grafts. Analysis of CD25, CD95, HLA-DR, and CD45RA expression shows that T-cell activation level was lower after granulocyte colony-stimulating factor mobilization. Similarly, granulocyte colony-stimulating factor reduced by twofold to threefold the percentage of interferon-gamma, interleukin-2, and tumor necrosis factor-alpha-secreting cells within the NK, NK-T, and T-cell subsets and severely impaired the potential for interferon-gamma production at the single-cell level. mRNA levels of both type 1 (interferon-gamma, interleukin-2) and type 2 (interleukin-4, interleukin-13) cytokines were approximately 10-fold lower in peripheral blood stem cell grafts than in bone marrow grafts. This reduced potential of cytokine production was not associated with a preferential mobilization of so-called "suppressive" cells (CD3+CD4-CD8-, CD3+CD8+CD56+, or CD3+TCRVA24+CD161+), nor with a modulation of killer cell receptors CD161, NKB1, and CD94 expression by NK, NK-T, or T cells. Our data demonstrate in a randomized setting that quantitative as well as qualitative differences exist between a bone marrow and a peripheral blood stem cell graft, whose ability to produce type 1 and type 2 cytokines is impaired.

B-Lymphocytes↗
PubMed2001

High resolution HLA class I and II typing and CTLp frequency in unrelated donor transplantation: a single-institution retrospective study of 69 BMTs.

UNLABELLED: The results of unrelated donor transplantation (URD-BMT) are difficult to analyze since the continuous advances in HLA typing technology allow the detection of new mismatches unknown at the time of transplantation. We sought to confirm that matched recipient-donor pairs are in fact often mismatched when advanced HLA typing techniques are used. We retrospectively studied the impact of the results of high resolution HLA typing for HLA class I (-A, -B, -C) and HLA class II (-DR, -DQ, -DP) loci, and cytotoxic T lymphocyte precursor (CTLp) frequency, on the outcome of 69 URD-BMT procedures. At the time of transplant, six (6/69) and two (2/69) donor-recipient pairs were mismatched for HLA class I (-A and -B by serology) and HLA class II, respectively, while one pair was mismatched for both HLA class I and II. Using high resolution DNA typing, HLA class I mismatches were found in 31 (45%) pairs and HLA class II mismatches in nine (13%) pairs. Twenty-three of the 69 pairs were HLA-C mismatched. Low CTLp frequencies were found among the 19 HLA class I matched pairs tested, and also in 5/14 mismatched pairs (of whom three had severe aGVHD). The overall survival of the cohort was 28 +/- 6%. Among the 33 patients who were fully matched with their donors, the survival rate was 66% in the 18 patients with a standard hematological risk and 9% in the 15 high risk patients. Only two of the 33 patients developed severe aGVHD, and only one had graft rejection. Among the 36 mismatched pairs, the survival rate was 31% in the 13 patients with a standard hematological risk and 8% in the 23 high risk patients. Sixteen of these 36 patients died from severe aGVHD and four had graft failure or rejection. Three of the 10 patients with only an HLA-C mismatch died from severe aGVHD, and two had graft rejection. IN CONCLUSION: (1) donor-recipient matching based on high resolution HLA class I and II DNA typing is associated with significantly better outcome after URD-BMT; (2) the results of URD-BMT with classical GVHD prevention are comparable to those of geno-identical BMT when donor and recipient are fully matched for HLA-A, -B, -C, -DRB1 and -DQB1 on the basis of high resolution typing; (3) CTLp frequencies do not correlate constantly with HLA class I matching, and our results fail to show that CTLp assay can distinguish between permissible and non-permissible class I mismatches; (4) clinical trials involving donor-recipient pairs with known HLA class I mismatches are needed to improve aGVHD prevention without increasing graft failure rate.

Adult↗
PubMed2001

Allogeneic peripheral blood stem cell transplantation results in less alteration of early T cell compartment homeostasis than bone marrow transplantation.

Since low T cell counts evaluated 1 month after allogeneic bone marrow transplantation (BMT) are associated with an increased risk of leukemia relapse (Powles et al., Blood 1998; 91: 3481-3486), we compared, in a randomized multicentric clinical study, the peripheral blood cells obtained 30 days after allogeneic BMT vs allogeneic G-CSF-mobilized peripheral blood stem cell transplantation (BCT) in an HLA-identical setting. T cell counts were higher 30 days after BCT (718+/-142 cells/microl, n = 20) than after BMT (271+/-53 cells/microl, n = 26, P = 0.006). However, T cells were less activated after BCT than after BMT, as demonstrated by a lower expression level of CD25 and a lower percentage of HLA-DR+ and CD95+ T cells. Furthermore, CD4+, CD8+ and CD45RA+ post-BCT T cell counts correlated with the number of cells infused with the PBSC graft, while such a correlation was not observed between post-BMT counts and BM graft cell numbers, suggesting that the intensity of post-transplant peripheral lymphoid expansion and/or deletion differed between BCT and BMT. A comparison of the input of T cells expressing different CD45 isoforms with the post-transplant cell recovery further confirmed that, within the CD4+ T cell subset, post-transplant expansions occurred at a higher level after BMT than after BCT, affecting mainly the CD4+ CD45RO+ subset. Altogether, our data demonstrate for the first time in a randomized setting that homeostasis of the T cell pool is less altered early after BCT than after BMT. This may have a strong impact on the graft-versus-leukemia (GVL) effect and subsequent relapse rate.

Adult↗
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

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↗