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U W Schaefer

Publications and source records attributed to U W Schaefer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Bone marrow engraftment: histopathology of hematopoietic reconstitution following allogeneic transplantation in CML patients.

Following myelo-ablative treatment and allogeneic bone marrow transplantation (BMT) in chronic myelogenous leukemia (CML) histopathological features assumed to exert a significant impact on engraftment have been rarely investigated systematically. This review is focused on immunohistochemical and morphometric techniques involving nucleated erythroid precursors, resident macrophages and their various subsets, megakaryocytes and finally argyrophilic (reticulin-collagen) fibers. Regarding standardized intervals of examination in the postgraft sequential trephine biopsies a pronounced reduction in cellularity was obvious and accompanied by a decrease in the quantity of erythro- and megakaryopoiesis. A significant correlation between the number of erythroid precursors and CD68+-macrophages could be determined in the areas of regenerating hematopoiesis. This finding is in keeping with the important functional role of the centrally localized mature macrophages during erythropoiesis. A relevant pretransplant reduction of the red cell lineage and an early to advanced reticulin fibrosis were correlated with a low hemoglobin level (anemia) and splenomegaly and furthermore associated with a significant delay to reach transfusion independence. This result was supported by corresponding findings in biopsy specimens performed shortly after day 30 following BMT (standard interval for assessment of engraftment). Samples revealed an enhancement of fiber density and a conspicuous decrease in the amount of erythropoiesis in the small fraction of patients who did not conform with the usually accepted criteria for successful hematopoietic reconstitution. Considering the compartment of histiocytic reticular cells the recurrence of Pseudo-Gaucher cells (PCGs) in the engrafted donor marrow was remarkable and most prominently expressed in the first two months following BMT. This feature was presumed to be functionally linked with a pronounced degradation of cell debris in the sequel of myelo-ablative therapy (scavenger macrophages). According to planimetric measurements in the postgraft bone marrow the atypical dwarf-like CD61+-megakaryocytes characteristic for CML disappeared. On the other hand, normalization of megakaryocyte size and nuclear lobulation were absent in sequential examination of the few patients developing a leukemic relapse. In a number of patients with manifest myelofibrosis at onset, an initial regression after BMT was followed by an insidiously occurring retrieval which was concentrated on the areas of reconstituting hematopoiesis. Similar to its relevant pretransplant association the postgraft reappearance of myelofibrosis was significantly correlated with the quantity of CD61+-megakaryocytes. Altogether a number of histological features in the pre-and postgraft bone marrow exhibited significant correlations with each other and thus indicated functional relationships. Moreover, quantity of erythropoiesis and amount of reticulin fibers (myelofibrosis) exerted a significant impact on engraftment status.

Animals↗
PubMed2000

Effect of centre on outcome of bone-marrow transplantation for acute myeloid leukaemia. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation.

BACKGROUND: There is increasing pressure for the recognition and replication of good clinical practice. We undertook a study to assess the variability in outcome of allogeneic bone-marrow transplantation among major European centres. METHODS: We studied 13 centres, including 522 patients (aged 16-55 years), which had undertaken more than 30 bone-marrow transplantations between Jan 1, 1987, and Dec 31, 1995, for acute myeloid leukaemia in first complete remission. We undertook a (global) multivariate analysis of all factors known previously to influence outcome and a stratified analysis that initially defined, by multivariate analysis, significant variables in this study and then used a proportional-hazard model including centres. FINDINGS: The overall results at 3 years were 57% (95% CI 53-61) for leukaemia-free survival (LFS), 23% (19-27) for relapse incidence (RI), and 26% (22-30) for treatment-related mortality (TRM) with a range for centres of 36-75%, 10-37%, and 8-54%, respectively. Both methods of analysis showed the centre effect to be highly significant for LFS and TRM, but not for RI. Variables associated with a significantly poor outcome were age over 43 years (p=0.01), time from diagnosis to first complete remission longer than 65 days (p=0.02), and centre (p=0.013) for LFS, and age over 43 years (p=0.023), time from first complete remission to transplantation of longer than 93 days (p=0.03), and centre (p=0.001) for TRM. Moreover, different centres had different prognostic criteria for good-risk or bad-risk patients indicating that risk factors do not have the same impact in each individual centre. INTERPRETATION: The outcome of bone-marrow transplantation for acute myeloid leukaemia in first complete remission is influenced by the centre in which the procedure is done, even with adjustment for known prognostic risk factors. Significant prognostic factors vary among centres, which means that the relative risk is not the same in each individual centre. However, centres may treat populations with different risks of as yet unidentified prognostic factors. Experience may partly account for the difference in outcome among centres.

Adolescent↗
PubMed2000

Bone loss in long-term survivors after transplantation of hematopoietic stem cells: a prospective study.

Organ transplantation is associated with relevant bone loss. Bone loss of up to 20% of pretransplant bone mineral density (BMD) values within the first year after kidney, liver, heart and lung transplantation has been reported. Patients undergoing transplantation of hematopoietic stem cells provide an interesting model to study transplantation-induced bone loss, especially because most patients do not have preexisting bone disease. A longitudinal study was performed in 81 patients undergoing bone marrow or peripheral blood stem cell transplantation. BMD was determined by dual-energy X-ray absorptiometry before transplantation, at discharge from the hospital, and at 6 and 12 months after transplantation in all 81 patients. In 35 patients BMD was re-evaluated 24 months after transplantation. Vitamin D and parathyroid hormone, bone alkaline phosphatase as a marker of bone formation, and N-terminal telopeptide of type I collagen as a marker of bone resorption were assessed before transplantation and in the short-term follow-up 14 and 28 days after transplantation. The majority of patients (72%) showed normal BMD before transplantation. However, lower BMD was observed in patients who had received high-dose cytoreductive chemotherapy before transplantation compared with those who had received no chemotherapy or only hydroxyurea. Despite supplementation with elemental calcium (1000 mg/day) and vitamin D (1000 IU/day), the mean rate of bone loss during the first year was 7.2 +/- 6.3% at the lumbar spine, 11.9 +/- 8.1% at the femoral neck and 3.8 +/- 2.5% at the total body compartment. Evaluation of the pattern of bone loss during the first year demonstrated that the amount of bone loss was largest within the first 40 days after transplantation and small during the second half of the first year after transplantation. The majority of patients showed vitamin D deficiency and secondary hyperparathyroidism. Bone formation was normal before and after transplantation, whereas bone resorption was dramatically increased before and after transplantation. Exposure to glucocorticoids was associated with higher bone loss at spine and femoral neck but not at the total body compartment. Our data demonstrate rapid bone loss in patients undergoing transplantation of hematopoietic stem cells. Bone turnover is characterized by biochemical uncoupling of bone resorption and bone formation, changes interestingly pre-existing before transplantation. The observed alterations in bone mass and metabolism emphasize the importance of clinical trials with antiresorptive agents to prevent and treat post-transplantation osteoporosis in this group of patients.

Adolescent↗
PubMed2000

The amount of BCR-ABL fusion transcripts detected by the real-time quantitative polymerase chain reaction method in patients with Philadelphia chromosome positive chronic myeloid leukemia correlates with the disease stage.

The use of the real-time reverse-transcription polymerase-chain reaction (RT-PCR) method to quantify BCR-ABL transcripts before and after allogeneic transplant was prospectively studied in 65 patients with chronic myeloid leukemia (CML). The expression of the BCR-ABL transcript was determined and normalized using the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) housekeeping gene product as an endogenous reference. In the single step real-time PCR assay, tenfold serial dilutions of cDNA of the K5652 cell line remained positive down to 100 pg cDNA only. However, molecular relapses of CML after transplant were only safely detectable when a nested real-time PCR assay was performed, which was able to detect 1-10 pg cDNA from a tenfold serial dilution. The median normalized BCR-ABL transcript level was measured as 0.004% in 17 patients with a molecular relapse, 0.4% in 7 patients with a cytogenetic relapse, 2.6% in 36 patients with a stable phase of CML, and 36% in 5 patients with a relapse in a blast crisis. The analyzed median normalized amount of BCR-ABL transcript differed significantly (P<0.001) between the various disease stages. In ten CML patients with relapse, the real-time PCR method was used to monitor the response of various immunotherapies as donor leukocyte infusions, withdrawal of immunosuppression, or interferon-alpha application. The results of the quantitative evaluation of BCR-ABL transcripts reflected very well the clinical effect of the different applied immunotherapies. The new real-time PCR method seems to be a suitable technique for the early detection of relapse after allogeneic transplant in patients with the BCR-ABL transcript. Its ability to distinguish between molecular and cytogenetic relapse (P<0.001) allows early therapeutic decisions.

Bone Marrow Transplantation↗
PubMed2000

Transplant activities in Germany in 1998--a survey facilitated by the National Registry for Hemopoietic Stem Cell Transplantation.

To improve the infrastructure of hemopoietic stem-cell transplantations in our country, the German Registry for Hemopoietic Stem-Cell Transplantations (DRST) was established in 1998. The present paper summarizes the current status of the DRST and gives a survey of transplant activities in Germany in 1998 in terms of transplant units, transplant types, transplant frequencies and underlying diseases.

Blood Cells↗
PubMed2000

Macrophages and their subpopulations following allogenic bone marrow transplantation for chronic myeloid leukaemia.

A morphometric and immunohistochemical study was performed on 354 bone marrow trephine biopsies derived from 126 patients with chronic myeloid leukaemia (CML) before and after allogeneic bone marrow transplantation (BMT). The purpose of this investigation was to evaluate the macrophage population, including several subsets and their dynamics in the posttransplant period. In addition to the total CD68+ resident (mature) macrophages the so-called activated fraction identified by its capacity to express alpha-D-galactosyl residues, the pseudo-Gaucher cells (PGCs) and the iron-laden histiocytic reticular cells were also considered. Following immuno- and lectin-histochemical staining morphometric analysis was carried out on sequential postgraft bone marrow specimens at standardized intervals. Compared to the normal bone marrow and calculated per haematopoiesis (cellularity) an overall decrease of about 40-50% in the quantity of CD68+ macrophages and the BSA-I+ subpopulation was detectable in the early posttransplant period (9-45 days after BMT). Noteworthy was the temporal recurrence of PGCs in the engrafted bone marrow, which was not associated with a clonally transformed cell population or leukaemic relapse. Reappearance of postgraft PGCs was most prominent in the first 2 months after BMT. This conspicuous feature was presumed to be functionally associated with a pronounced degradation of cell debris following pretransplant myelo-ablative therapy (scavenger macrophages). Evidence for an activation of the BSA-I+ macrophage subset was derived from the identical carbohydrate-binding capacity shown by the PGCs. In the regenerating haematopoiesis shortly after BMT a significant correlation between the number of BSA-I+ macrophages and erythroid precursor cells was determinable. This result implicates a close functional relationship between postgraft reconstitution of erythropoietic islets and centrally localized activated macrophages. In conclusion, findings emerging from this study included the reappearance of PCGs in the engrafted bone marrow independently of a leukaemic relapse and the significant association of the activated BSA-I+ macrophage subset with the recovery of erythropoiesis.

Adult↗
PubMed2000

The detection of wt-1 transcripts is not associated with an increased leukemic relapse rate in patients with acute leukemia after allogeneic bone marrow or peripheral blood stem cell transplantation.

We studied the role of wt-1 as a minimal residual disease (MRD) marker in 46 patients with acute leukemia (AL) (1st CR n = 24; 2nd CR n = 9, in relapse n = 13) after allogeneic bone marrow or peripheral blood stem cell transplantation. Prior to allogeneic transplant, wt-1 transcripts were detected by PCR in 38 of 46 patients (83%) with AL. After transplant, in 14 of 38 patients (37%) wt-1 transcripts were detected in at least one PCR assay at a median of 12 months post transplant (range 1-89 months). Twelve of the 38 patients relapsed after transplant, but only seven of the 12 were wt-1 positive after transplant. In five relapsing patients the wt-1 test remained negative 0 to 3 months prior to relapse. On the other hand, only seven of 14 patients with a positive test for wt-1 after transplant, relapsed consecutively. In 17 of the 46 study patients chromosomal abnormalities had been found prior to transplant (AML-M4eo with inv16 n = 7, AML-M2 with t(8;21) n = 3, AML-M3 with t(15;17) n = 1, AML-M5 with t(4;11) n = 1, ALL with t(9;22) n = 5). In these 17 patients, we analyzed the wt-1 transcript simultaneously with a specific chimeric transcript characteristic for the corresponding chromosomal abnormality. In 32 of 45 samples (71%) the results for the MRD marker and wt-1 transcript were concordant, but differed in 13 patients. We conclude that detection of wt-1 transcripts does not predict leukemic relapse reliably and is therefore not a suitable MRD marker in patients with acute leukemia after allogeneic BM or PBSC transplantation. Bone Marrow Transplantation (2000) 25, 91-96.

Acute Disease↗
PubMed2000

Reduced risk of persisting cytomegalovirus pp65 antigenemia and cytomegalovirus interstitial pneumonia following allogeneic PBSCT.

In order to evaluate the risk of cytomegalovirus (CMV) associated disease after allogeneic stem cell transplantation (SCT), 158 consecutive patients at risk for infection were analyzed. BMT was performed in 101 patients and peripheral blood stem cell transplantation (PBSCT) in 57 patients. CMV antigenemia was found in 57 cases (56%) after BMT and 27 cases (47%) after PBSCT, respectively. CMV antigenemia resistant to a 14-day course of GCV was found in 26 patients (26%) after BMT but in only four patients (7%) after PBSCT (P < 0.01). Eighteen patients (11%) developed CMV disease, 14 post BMT and four post PBSCT. Lethal CMV-related interstitial pneumonia (CMV-IP) occurred in 13 cases of whom 12 patients were bone marrow recipients (P = 0.04). The subgroup of seronegative patients with a CMV seropositive donor had a significantly lower risk of developing CMV antigenemia, GCV-resistant CMV antigenemia (P < 0.01) and CMV-related disease (P = 0.01). In conclusion, the incidence of persistent CMV antigenemia and CMV-IP was significantly reduced when allogeneic transplantation was performed with peripheral blood stem cells instead of bone marrow. These findings suggest that our previous in vitro data on improved immune reconstitution after allogeneic PBSCT as compared to allogeneic BMT have clinical relevance.

Adolescent↗
PubMed2000

Relevance and dynamics of myelofibrosis regarding hematopoietic reconstitution after allogeneic bone marrow transplantation in chronic myelogenous leukemia--a single center experience on 160 patients.

A retrospective single center study was performed on 516 trephine biopsies derived from 160 patients with stable phase Ph+-CML and allogeneic BMT. Following morphometric quantification of reticulin-collagen fibers we tried to elucidate (1) the dynamics of bone marrow fibrosis in the post-transplant period; and (2) the influence of manifest myelofibrosis on relevant engraftment parameters. An evaluation of fiber density at standardized endpoints after BMT was carried out on a selected cohort of 124 patients (399 biopsy specimens). A manifest myelofibrosis (more than a three-fold increase compared to the normal fiber content) before BMT was found in 26% of our patients. Concentrating on bone marrow areas with reconstituting hematopoiesis, several findings emerged. Pretransplant myelofibrosis was associated with an initial regression following BMT, but insidiously recurred in the areas of regenerating hematopoiesis or developed in a few patients without increased pregraft fibers during the post-transplant period (mean observation time more than 4 months). Severe acute GVHD (grades III and IV) was significantly correlated with a greater amount of reticulin fibers in the early post-transplant period (9 to 30 days after BMT). Regarding engraftment parameters, a significant delay was detectable in the time to achieve transfusion independence for the patients with manifest myelofibrosis compared to those without pre-transplant fiber increase.

Adolescent↗
PubMed2000

Human herpesvirus 6 is an important pathogen in infectious lung disease after allogeneic bone marrow transplantation.

Two hundred and ten bronchoalveolar lavage (BAL) samples were obtained from 50 patients 10 days before and on defined days after allogeneic bone marrow transplantation (BMT). The samples were examined for human cytomegalovirus (HCMV) and human herpesvirus-6 (HHV-6) by polymerase chain reaction (PCR). Fifteen patients (30%) had a positive result for HCMV in at least one sample and 25 (50%) were positive for HHV-6 in at least one sample. Five patients developed HCMV-associated interstitial pneumonia (HCMV-IP) within 100 days after allogeneic BMT. Four of these patients were positive for both HCMV and HHV-6. Conspicuous HHV-6 positivity was detected in BAL samples obtained because of respiratory symptoms. No association was found between detection of HHV-6 and acute graft-versus-host disease. Engraftment failure or a delay in engraftment was observed in none of the 50 patients. The data from this study indicate that HHV-6 is a pathogen in HCMV-associated, as well as in non-HCMV-associated infectious lung disease after BMT.

Acute Disease↗
PubMed2000

Transplantation of highly purified HLA-identical sibling donor peripheral blood CD34+ cells without prophylactic post-transplant immunosuppression in adult patients with first chronic phase chronic myeloid leukemia: results of a phase II study.

The feasibility of transplantation using highly purified G-CSF-mobilized peripheral blood CD34+ cells from HLA-identical sibling donors without prophylactic post-transplant immunosuppression was prospectively studied in 10 adult first chronic phase chronic myeloid leukemia (CML) patients with special reference to graft engineering performance and follow-up studies of minimal residual disease and immune reconstitution. CD34+ cells were enriched by clinical-scale magnetic-activated cell separation (MACS) using iron-dextran beads bound to monoclonal anti-CD34 antibody. Grafts contained a median of 9.7 (range 1.7-16.6) x 10(6) CD34+ cells per kilogram of recipient body weight with a purity between 94.5% and 98.3% (median 97.2%). The median number of transfused CD3+ T lymphocytes was 1.0 (range 0.5-8.5) x 10(4)/kg, corresponding to a log10 T lymphocyte depletion between 3.8 and 5.0 (median 4.6). All patients engrafted rapidly with a median duration to neutrophil counts >500/microl of 8 (range 8-19) days and to self-sustaining platelet counts >20,000/microl of 12 (range 9-25) days. Isolated skin acute graft-versus-host disease (GVHD) of stages I to II occurred in three patients. One patient developed secondary graft failure and was successfully salvaged by an unmanipulated blood stem cell graft from the same donor. All 10 patients are surviving in complete hematologic, cytogenetic and molecular remission (four patients after donor lymphocyte infusions) between 12 and 22 (median 16) months post transplant. In conclusion, transplantation of MACS-purified blood CD34+ cells from HLA-identical sibling donors in adult CML patients appears safe, effectively prevents acute GVHD without prophylactic post-transplant immunosuppression, and is capable of inducing complete cytogenetic and molecular remissions.

Adolescent↗
PubMed2000

Fungal colonization and invasive fungal infections following allogeneic BMT using metronidazole, ciprofloxacin and fluconazole or ciprofloxacin and fluconazole as intestinal decontamination.

Invasive fungal infections (IFI) are increasingly diagnosed in patients undergoing allogeneic BMT. We have previously shown that the addition of metronidazole to ciprofloxacin for gastrointestinal bacterial decontamination significantly reduces the incidence of grades II-IV aGVHD by reduction of the anaerobic intestinal bacterial flora. Here, we found that the combined use of ciprofloxacin, metronidazole and fluconazole as antifungal prophylaxis increased intestinal yeast colonization when compared to ciprofloxacin and fluconazole alone (P < 0.01). Based on the EORTC criteria, a total of 18 out of 134 study patients developed IFI: seven of 68 (10%) patients who received metronidazole compared to 11 of the 66 (17%) patients decontaminated without metronidazole developed IFI (log-rank P = 0.36). Lethal IFI occurred in two of seven patients receiving metronidazole and in four of 11 patients without anaerobic decontamination. In conclusion, bacterial intestinal decontamination using metronidazole as an antibiotic with activity against most anaerobic intestinal bacteria significantly increases the intestinal yeast burden without influencing the incidence of IFI in patients undergoing allogeneic BMT.

Adolescent↗
PubMed2000

Erythropoietic reconstitution, macrophages and reticulin fibrosis in bone marrow specimens of CML patients following allogeneic transplantation.

A clinicopathological study was conducted on 351 bone marrow trephine biopsies derived from 124 patients with chronic myeloid leukemia (CML) at standardized endpoints before and after allogeneic bone marrow transplantation (BMT). The purpose was to investigate quantitative changes of the nucleated erythroid precursor cell population and other associated features such as resident bone marrow macrophages and myelofibrosis and to elucidate their relevance on engraftment parameters. Monoclonal antibodies were applied for the identification of erythroid precursors and the labeling of mature macrophages; argyrophilic (reticulin-collagen) fibers were demonstrated by a silver impregnation technique. Following morphometric analysis of the pregraft bone marrow specimens statistical evaluation was in line with an adverse correlation between early to moderate reticulin fibrosis and amount of erythropoiesis. Moreover, a significant relationship was calculable between numbers of erythroid precursors and CD68+ macrophages. After myelo-ablative therapy and BMT a pronounced decrease in cellularity and in the quantity of erythropoiesis was found. Comparable with the pregraft samples, a significant association between erythroid precursors and macrophages could be determined in the regenerating donor bone marrow. A pretransplant relevant reduction of the red cell lineage and a manifest (reticulin) myelofibrosis indicating an advanced stage of disease were accompanied by a significant delay to reach transfusion independence. This result was further supported by comparable findings in trephine biopsies performed in the early post-transplant period (second month after BMT). Corresponding examinations revealed an enhancement of fiber density and a decrease in erythropoiesis in those patients who did not conform with the usually accepted criteria for successful engraftment. In conclusion, compelling evidence has been produced that a significantly reduced amount of erythroid precursors, which is usually associated with myelofibrosis in the pretransplant bone marrow, exerts an impairment to undisturbed hematopoietic reconstitution. Moreover, a close spatial and numerical relationship between the erythroid lineage and resident (mature) macrophages is observable, in particular in the state of regeneration after BMT.

Adolescent↗
PubMed2000

Haematopoietic stem cell transplantation for amegakaryocytic thrombocytopenia.

Congenital amegakaryocytic thrombocytopenia (CAT), a rare syndrome with failure of megakaryopoiesis, cannot be cured by immunoglobulins, steroids or cyclosporin, but only by allogeneic bone marrow transplantation (BMT). We report on eight patients with CAT, all of whom were dependent at the time of BMT on platelet transfusion. Sources of haematopoietic progenitor cells were bone marrow (n = 5), peripheral stem cells (n = 2) and cord blood (n = 1). Seven patients engrafted. Both patients with matched unrelated donor transplants died, six patients are well with stable platelet counts 3-27 months after transplantation. BMT represents a curative option for CAT. The benefit of using alternative marrow donors should be carefully evaluated.

Bone Marrow Cells↗
PubMed2000

Is there a graft-versus-leukaemia effect in the absence of graft-versus-host disease in patients undergoing bone marrow transplantation for acute leukaemia?

During a 13-year period, 5200 autografts, 1039 HLA-identical sibling transplants without acute or chronic graft-vs.-host disease (GVHD) and 67 twins were reported to the European Group for Blood and Marrow Transplantation EBMT. Follow-up time was a median of 32 months. Diagnoses were acute myeloid leukaemia (AML, 4521) and acute lymphoblastic leukaemia (ALL, 1785) in first complete remission. The probability of relapse at 5 years was 51 +/- 1% in the autografts, 45 +/- 8% in the twins and 34 +/- 2% among the HLA-identical siblings (auto vs. sibs, P < 0.0001). In multivariate analyses, the following factors were significantly associated with an increased risk of relapse: ALL vs. AML M3 [relapse rate (RR) 2.29, P < 0.0001], AML non-M3 vs. AML M3 (RR 1.8, P < 0.0001), autograft vs. sibling transplant (RR 1.76, P < 0.0001), interval diagnosis to transplantation < 261 d (RR 1.45, P < 0.001) and other conditioning vs. total body irradiation (RR 1.16, P = 0.001). Transplant-related mortality was the same in the three groups at approximately 10% at 2 years. Five-year leukaemia-free survival was 42 +/- 1% in the autografts, 44 +/- 8% in the twins and 58 +/- 2% among the siblings (auto vs. sibs, P < 0.0001). The factors significant for relapse were also significant in multivariate analyses for leukaemia-free survival. In addition, children had a significantly better leukaemia-free survival than adults (RR 0.82, P < 0.0001). Recipients of bone marrow from HLA-identical siblings without GVHD had a lower risk of relapse and a better leukaemia-free survival than recipients of autografts. This may be as a result of a graft-vs.-leukaemia effect in the absence of GVHD.

Acute Disease↗
PubMed1999

The risk of residual molecular and cytogenetic disease in patients with Philadelphia-chromosome positive first chronic phase chronic myelogenous leukemia is reduced after transplantation of allogeneic peripheral blood stem cells compared with bone marrow.

The detection of residual molecular and cytogenetic disease was prospectively compared in patients with Philadelphia-chromosome (Ph1) positive first chronic phase chronic myelogenous leukemia (CML) who underwent allogeneic transplantation of unmanipulated peripheral blood stem cells (PBSCT) (n = 29) or bone marrow (BM) (n = 62) using genotypically HLA-identical sibling donors or partially HLA-matched extended family donors. A molecular relapse (MR), as defined by two consecutive positive polymerase chain reaction (PCR) assays for the detection of M-bcr-abl transcripts in a 4-week interval, was found in two of 29 (7%) patients after PBSCT compared with 20 of 62 (32%) patients after bone marrow transplantation (BMT). This corresponds to a 4-year molecular relapse estimate (+/- standard error) of 7% +/- 5% after PBSCT and of 44% +/- 8% after BMT (P <.009). With identical follow-up periods of survivors in both patient subsets between 6 and 55 months (median, 28 months), 14 of the 20 patients with MR after BMT progressed to an isolated cytogenetic (n = 10) or a hematologic (n = 4) disease recurrence, resulting in a 4-year cytogenetic relapse estimate of 47% +/- 11%, while none of the patients after PBSCT has so far relapsed (P <.006). Multivariate analysis including all potential influencial factors of posttransplant disease recurrence identified the source of stem cells (P <.02) as the only independent predictor of molecular relapse. In conclusion, this prospective comparison of molecular and cytogenetic residual disease demonstrates that peripheral blood stem cell transplants have a more pronounced activity against residual CML cells than bone marrow transplants. Prospective randomized trials comparing PBSCT and BMT in patients with first chronic phase Ph1-positive CML are strictly required to further substantiate differences in the antileukemic activity of the two stem cell sources.

Adolescent↗
PubMed1999

Influence of intestinal bacterial decontamination using metronidazole and ciprofloxacin or ciprofloxacin alone on the development of acute graft-versus-host disease after marrow transplantation in patients with hematologic malignancies: final results and long-term follow-up of an open-label prospective randomized trial.

In a single-center open-label prospective study, a total of 134 marrow transplant recipients with hematologic malignancies were randomly assigned to a bacterial decontamination medication using metronidazole and ciprofloxacin (n = 68) or ciprofloxacin alone (n = 66) during 5 weeks posttransplant. The development of grades II to IV acute graft-versus-host disease (GVHD) was defined as the primary study endpoint. According to the intention-to-treat, 17 patients (25%) randomized to the combined decontamination medication and 33 patients (50%) randomized to ciprofloxacin alone developed grades II to IV GVHD (P <.002). The higher frequency of grades II to IV acute GVHD in patients randomized to ciprofloxacin alone resulted from a more than twofold increased number of patients developing liver or intestinal involvement with acute GVHD compared with patients randomized to the combined decontamination medication (P <.003). The influence of the study medication on grades II to IV acute GVHD was significant only in recipients of transplants from genotypically HLA-identical sibling donors (n = 80), whereas in recipients of transplants from donors other than HLA-identical siblings (n = 54), grades II to IV acute GVHD frequencies between the study arms were not significantly different. The combined decontamination was associated with a significant reduction of culture growth of intestinal anaerobic bacteria during 5 weeks posttransplant (P <. 00001). In addition, the number of cultures with growth of anaerobic bacteria (P <.005) as well as the median concentrations of anaerobic bacteria in the posttransplant period (P <.0001) were higher in patients contracting grades II to IV acute GVHD. Neither chronic GVHD nor overall survival was significantly different between the two study arms. In patients with HLA-identical sibling donors who were treated in early disease stages, the 5-year survival estimate was slightly, but not significant, higher after the combined decontamination medication (60% +/- 11%) compared with ciprofloxacin alone (46% +/- 9%). In conclusion, the present study provides evidence that antimicrobial chemotherapy targeted to intestinal anaerobic bacteria in marrow transplant recipients significantly reduces the severity of acute GVHD and supports the theory that the intestinal anaerobic bacterial microflora plays a role in the pathogenesis of acute GVHD after human marrow transplantation.

Adolescent↗