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1.
Ann Oncol ; 22(7): 1614-1621, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21245159

ABSTRACT

BACKGROUND: Outcomes of Ewing tumor (ET) patients treated with allogeneic stem cell transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. PATIENTS AND METHODS: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts. RESULTS: Median overall survival was 7.9 months [±1.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (±1.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE). CONCLUSIONS: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocols.


Subject(s)
Bone Neoplasms/mortality , Bone Neoplasms/therapy , Graft vs Host Disease/therapy , Sarcoma, Ewing/mortality , Sarcoma, Ewing/therapy , Stem Cell Transplantation , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Survival Rate , Transplantation Conditioning , Transplantation, Homologous , Treatment Outcome , Young Adult
2.
Cell Prolif ; 43(6): 579-83, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21039996

ABSTRACT

OBJECTIVES: Proliferating cell nuclear antigen (PCNA) has often been used as a marker to aid assessment of tumour growth fraction. This paper addresses the question of whether it can be used as an S-phase marker, when the non-chromatin-bound form of the protein is removed by pepsin treatment. MATERIALS AND METHODS: Cytofluorometric measurements were carried out after immunofluorescence staining of PCNA and counterstaining of DNA. S-phase fraction was determined with the help of windows on PCNA versus DNA scattergrams, or mathematically from DNA histograms. RESULTS: S-phase fractions obtained using the two methods correlated well, but did not always agree, exact discrepancies depending on the mathematical model used for histogram analysis. CONCLUSIONS: Determination of S-phase fractions with the help of PCNA immunofluorescence staining is possible, and probably more reliable than calculation of S-fractions from DNA histograms. It thus offers an alternative to assays involving BrdU labelling in vivo.


Subject(s)
Chromatin/metabolism , Leukocytes, Mononuclear/metabolism , Multiple Myeloma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Proliferating Cell Nuclear Antigen/analysis , Proliferating Cell Nuclear Antigen/metabolism , S Phase/physiology , Adolescent , Adult , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Child , Child, Preschool , Female , Fluorescent Antibody Technique , Fluorescent Dyes/chemistry , Humans , Infant , Leukocytes, Mononuclear/pathology , Male , Middle Aged , Models, Biological , Multiple Myeloma/diagnosis , Multiple Myeloma/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Staining and Labeling
3.
Water Res ; 39(17): 4220-8, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16202441

ABSTRACT

The impact of a support material on an integrated biofilter-membrane system, simulating a difficult-to-treat surface water, was examined in terms of membrane fouling rate and water quality parameters. The support media in the membrane tanks did not generally affect any of the water quality parameters measured; however, there was an observable difference in the membrane fouling rates between the two processes with the support media system fouling at least two times slower than the non-support system. Total organic carbon (TOC) removals at around 60% were observed for two integrated biofilter-immersed membrane processes with the majority of the TOC removal occurring in the biofilters. One of the membrane tanks contained a support media (Process A) while the other did not (Process B). The feedwater contained humic acid (65% w/w) and readily biodegradable carbons (35% w/w) in the forms of acetic acid, formic acid and formaldehyde. The influent TOC values were between 3.35 and 3.94 mg/L. Acetate removals varied between 66 and 83%, while over 90% of the formate was removed and the formaldehyde was completely removed in the biofilters. There was a decrease in the UV absorbance values by over 70% for both processes.


Subject(s)
Filtration/instrumentation , Membranes, Artificial , Biodegradation, Environmental , Carbon , Microscopy, Electron, Scanning
4.
Methods Inf Med ; 43(2): 171-83, 2004.
Article in English | MEDLINE | ID: mdl-15136867

ABSTRACT

OBJECTIVE: Chemotherapy planning in pediatric oncology is complex and time-consuming. The correctness of the calculation according to state-of-the-art research is crucial for curing the child. Computer-assistance can be of great value. The objective of our research was to work out a meta-model of chemotherapy planning based on the Unified Modeling Language (UML). The meta-model is used for the development of an application system which serves as a knowledge-acquisition tool for chemotherapy protocols in pediatric oncology as well as for providing protocol-based care. METHODS: We applied evolutionary prototyping, software reengineering techniques and grounded theory, a qualitative method in social research. We repeated the following steps several times over the years: Based on a requirements analysis (i) a meta-model was developed or adapted, respectively (ii). The meta-model served as a basis for implementing evolutionary prototypes (iii). Further requirements were identified (i) from clinical use of the systems. RESULTS: We developed a comprehensive UML-based meta-model for chemotherapy planning in pediatric oncology (chemoMM). We implemented it and introduced evolutionary prototypes (CATIPO and DOSPO) in several medical centers. Systematic validation of the prototypes enabled us to derive a final meta-model which covers the requirements that have turned out to be necessary in clinical routine. CONCLUSIONS: We have developed an application system that fits well into clinical routine of pediatric oncology in Germany. Validation results have shown that the implementation of the meta-model chemoMM can adequately support the knowledge acquisition process for protocol-based care.


Subject(s)
Antineoplastic Agents/administration & dosage , Multi-Institutional Systems/organization & administration , Oncology Service, Hospital/organization & administration , Pediatrics , Therapy, Computer-Assisted , Germany , Humans
5.
Water Res ; 38(3): 655-62, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14723934

ABSTRACT

An integrated biofilter-immersed membrane study was conducted to determine the effect of placing a biofilter before or after a membrane for the treatment of a humic type water. The parameters measured included total organic carbon (TOC), organic acids, and specific ultraviolet absorbance (SUVA). The difference in membrane fouling and microbial growth for the two configurations was also examined. Greater TOC and organic acid removal occurred when the biofilter was located ahead of the membrane. The greatest decrease in SUVA values was associated with the membrane. The membrane located after the biofilter fouled at a slower rate than the membrane ahead of the biofilter. Fouling was slower when turbidity was present in the synthetic feedwater. A new method is proposed for determining the operational cleaning frequency of membranes, using an empirical model.


Subject(s)
Humic Substances , Models, Theoretical , Waste Disposal, Fluid/methods , Water Purification/methods , Bacteria , Filtration , Membranes, Artificial , Organic Chemicals/isolation & purification , Population Dynamics , Water Pollutants/isolation & purification
6.
Bone Marrow Transplant ; 33(2): 189-95, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14661036

ABSTRACT

Veno-occlusive disease (VOD) of the liver is a complication observed particularly in patients undergoing hematopoietic stem cell transplantation (HSCT). Defibrotide (DF) is a polydeoxyribonucleotide with aptameric activity on endothelium. We evaluated in a retrospective analysis the efficacy of DF in pediatric patients developing hepatic VOD after HSCT.A total of 45 patients between 0.2 and 20 years (median age: 8.2 years) with hepatic VOD were treated with DF: 22 patients (49%) met risk criteria for severe or progressive disease and 23 (51%) for moderately severe and mild disease. The median duration of DF treatment was 17 days. In all, 34 patients (76%) achieved complete response (CR) with a survival rate of 64% at day 100. CR rate in patients with severe disease was 50% with long-term survival of 36%. The average DF dose in the CR group was 45 mg/kg/day and in the no responder (NR) group 27 mg/kg/day. The use of additional drugs besides DF to treat VOD made no difference in the outcome compared to DF alone. The average interval from diagnosis to start of DF was 1 day in the CR and 5.5 days in NR group. In multivariate analysis, early intervention remained the only significant factor for a CR.


Subject(s)
Hematopoietic Stem Cell Transplantation , Hepatic Veno-Occlusive Disease/drug therapy , Platelet Aggregation Inhibitors/administration & dosage , Polydeoxyribonucleotides/administration & dosage , Adolescent , Adult , Child , Child, Preschool , Female , Hepatic Veno-Occlusive Disease/epidemiology , Humans , Infant , Infant, Newborn , Male , Platelet Aggregation Inhibitors/adverse effects , Polydeoxyribonucleotides/adverse effects , Retrospective Studies , Risk Factors , Severity of Illness Index , Transplantation Conditioning , Treatment Outcome
7.
Pediatr Hematol Oncol ; 21(8): 697-705, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15739624

ABSTRACT

Hepatic complications associated with cholestasis occur frequently in hematopoietic stem cell transplant recipients. Since bile acid seems to be a sensitive indicator of beginning cholestasis, the authors monitored total serum bile acid levels in addition to the standard liver function tests in 23 recipients of allogeneic transplants between June 1999 and September 2000. The observations suggest that bile acid is an early and sensitive marker of hepatic GvHD but not as specific as bilirubin. For cholestasis in absence of hepatic GvHD bile acid seems to be more sensitive than bilirubin. Routinely monitoring of bile acid after hematopoietic stem cell transplantation is not indicated.


Subject(s)
Cholestasis/diagnosis , Hematopoietic Stem Cell Transplantation/adverse effects , Adolescent , Bile Acids and Salts/blood , Bilirubin/blood , Biomarkers/blood , Child , Child, Preschool , Diagnosis, Differential , Female , Graft vs Host Disease/pathology , Hematologic Diseases/complications , Hematologic Diseases/therapy , Humans , Infant , Liver Diseases/etiology , Liver Function Tests , Male , Prospective Studies , Sensitivity and Specificity , Transplantation, Homologous
8.
J Clin Apher ; 18(3): 111-4, 2003.
Article in English | MEDLINE | ID: mdl-14569600

ABSTRACT

When harvesting peripheral progenitor cells (PPC) in children, the special situation of their circulatory system has to be taken into account. Therefore, extracorporeal blood volume and product volume should be small to avoid side effects. Nine children (age 2-14 years, weight 12.8-58.5 kg) with malignancies underwent 10 PPC collections with the MNC programme of the Amicus blood cell separator. The disposable kit was primed with red blood cells (RBCs) or human albumin to avoid circulatory side effects. The children were monitored for blood pressure and heart rate during the whole apheresis procedure. A median blood volume of 4,577 ml (range 3,536-8,596 ml) was processed in a separation time of 270 min (range 176-331 min). The median product weight was 81 g (range 53-107 g) and the yield of CD 34 antigen expressing cells was 12.5 x 10(6)/kg body weight (range 1.8-26 x 10(6)/kg body weight). Only one child had to undergo a second apheresis to collect the desired transplantation dose. The median platelet contamination of the product was 0.32 x 10(11) (0.13-0.85 x 10(11)). No circulatory side effects were observed. Blood flow alarms occurred in seven of ten aphereses and one collection had to be terminated due to insufficient flow. PPC can be efficiently collected in children with the MNC programme without circulatory side effects. The platelet contamination of the product was low due to the elutriation principle of the collection process, thereby avoiding thrombocytopenic bleeding episodes in the patients.


Subject(s)
Blood Component Removal/methods , Leukapheresis/methods , Leukocytes/cytology , Stem Cells/cytology , Adolescent , Albumins/metabolism , Antigens, CD34/biosynthesis , Antigens, CD34/metabolism , Blood Platelets/metabolism , Body Weight , Child , Child, Preschool , Erythrocytes/cytology , Humans , Neoplasms/therapy , Time Factors
9.
Bone Marrow Transplant ; 29(1): 9-13, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11840138

ABSTRACT

Allogeneic peripheral stem cell transplantation in six children with non-malignant hematologic or metabolic diseases which are eventually fatal was carried out with parental donors. Given three to five HLA mismatches, all grafts underwent CD34+ cell selection as graft-versus-host prophylaxis. The patients received median doses of 16.7 x 10(6) CD34+ cells/kg and 1.2 x 10(4) CD3+ cells/kg. All transplants engrafted. Neutrophils >0.5/nl were reached on day 11 (9-19) and platelets >50/nl on day 13 (10-25). Acute GVHD responding to steriods occured in three of six patients; it was restricted to the skin and overall did not exceed grade I. Two patients died of viral infections and four are alive with stable blood counts for 13, 15, 25 and 26 months. For children with non-malignant diseases which will eventually be fatal and which can be cured or ameliorated by allogeneic BMT, CD34+-selected stem cell transplants from mismatched or even haploidentical parents can be used if no other suitable donor is available. With high CD34+ cell doses and low CD3+ cell numbers, engraftment and avoidance of acute GVHD can be expected. Infections after transplantation remain the primary threat to survival.


Subject(s)
Peripheral Blood Stem Cell Transplantation/methods , Transplantation Immunology , Acute Disease , Antigens, CD34 , Blood Cells/transplantation , Blood Donors , Cause of Death , Graft Survival/physiology , Graft vs Host Disease/drug therapy , Parents , Peripheral Blood Stem Cell Transplantation/adverse effects , Peripheral Blood Stem Cell Transplantation/mortality , Survival Rate , Transplantation, Homologous/immunology , Transplantation, Homologous/methods , Transplantation, Homologous/mortality
10.
Bone Marrow Transplant ; 28(1): 51-7, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11498744

ABSTRACT

The incidence of adenovirus (AV) infections following SCT was determined in a prospective multicenter trial. Over 1 year, 130 consecutive patients undergoing allogeneic SCT at Essen University Hospital were included and followed for 6 months. Source of stem cells was blood in 68 cases. Fifty-eight patients had HLA-identical sibling donors. Throat swabs, urine and stool samples were screened weekly for AV antigen and DNA by ELISA and nested PCR, respectively. In 35 cases adenovirus infection was detected. There was no seasonal variation. Throat swabs were positive in 24, urine in 12, and stool in 11 cases, resulting in a cumulative risk of infection of 29%. The incidences of AV infection of the respiratory, gastrointestinal and urinary tract were 19%, 10%, and 9%, respectively, and infections were diagnosed after a median (range) interval of 44 (-2-179), 37 (-2-168), and 53 (17-153) days after transplantation. On multivariate analysis, presence of AV antibody in the donor and acute graft-versus-host disease grade IV were found to be independent risk factors for AV infection. Eleven patients had AV isolated from more than one site and five patients had probable AV disease. We were not able to identify patients in whom AV infection was the leading cause of death. The majority of patients infected with AV suffered from severe acute graft-versus-host disease often accompanied by other opportunistic infections, such as aspergillosis or CMV reactivation. Nineteen out of 36 patients who died during the observation period had AV infection. In summary, AV infection after allogeneic SCT was observed in a substantial number of patients. In addition to well-known risk factors for viral infection after SCT we were able to demonstrate that a positive AV antibody test in the donor is an important risk factor for AV infection. Further studies are needed, however, before final conclusions on the clinical sequelae of AV infection can be made and the role of preventive and therapeutic strategies toward AV infection after allogeneic SCT can be defined.


Subject(s)
Adenovirus Infections, Human/etiology , Transplantation, Homologous/adverse effects , Actuarial Analysis , Adenovirus Infections, Human/diagnosis , Adenovirus Infections, Human/mortality , Adolescent , Adult , Antibodies, Viral , Antigens, Viral/analysis , Blood Donors , Child , Child, Preschool , DNA, Viral/analysis , Female , Gastrointestinal Diseases/etiology , Gastrointestinal Diseases/virology , Hematologic Neoplasms/complications , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Incidence , Infant , Male , Middle Aged , Population Surveillance , Prospective Studies , Respiratory Tract Infections/etiology , Respiratory Tract Infections/virology , Risk Factors , Seasons , Time Factors , Urinary Tract Infections/etiology , Urinary Tract Infections/virology
11.
Bone Marrow Transplant ; 27(1): 111-3, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11244448

ABSTRACT

A 14-year-old girl developed very severe aplastic anemia unresponsive to steroids, cyclosporine, ATG and filgrastim. She experienced repeated bacterial infections, hypermenorrhagia and epistaxis and received numerous transfusions. Lacking a matched family or unrelated donor, she was transplanted 6 months after diagnosis with CD34+ cell-enriched peripheral stem cells from her HLA-haploidentical uncle. Conditioning included fludarabine, cyclophosphamide, 800 cGy TLI and OKT3. Prompt and sustained trilineage engraftment occurred. Acute GVHD grade 1 and herpes esophagitis were successfully treated. Eight months after grafting she was well with stable hematopoiesis. She then succumbed to fulminant hepatic failure due to adenovirus infection.


Subject(s)
Anemia, Aplastic/therapy , Antigens, CD34/blood , Haplotypes/immunology , Hematopoietic Stem Cell Transplantation , Stem Cells/immunology , Adenoviridae Infections/etiology , Adolescent , Anemia, Aplastic/complications , Female , Graft Survival , Hematopoiesis , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Histocompatibility Testing/standards , Humans , Liver Failure/virology , Transplantation Conditioning
12.
Br J Haematol ; 109(4): 773-5, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10929028

ABSTRACT

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.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Megakaryocytes , Thrombocytopenia/genetics , Thrombocytopenia/surgery , Bone Marrow Cells , Child , Child, Preschool , Female , Fetal Blood , Follow-Up Studies , Humans , Infant , Male , Survival Rate , Thrombocytopenia/mortality , Transplantation, Homologous , Treatment Outcome
13.
Bone Marrow Transplant ; 25 Suppl 2: S6-8, 2000 May.
Article in English | MEDLINE | ID: mdl-10933177

ABSTRACT

Engraftment was achieved in 43/45 (95%) recipients of peripheral blood stem cells (PBSC) from HLA-compatible unrelated donors (n = 45), compared to all 45 patients in matched controls receiving bone marrow and 14/18 (78%) recipients of CD34-selected PBSC (P < 0.01). The time to reach ANC >0.5 x 10(9)/l was a median of 16 days in the PBSC and CD34 groups, compared to 20 days in the bone marrow controls (P < 0.001 vs PBSC). The time to reach platelets >50 x 10(9)/l was a median of 23 days in the PBSC group and 24 days in the CD34 group, which was significantly faster than 29 days in the bone marrow controls (P < 0.01). Acute GVHD grades II-IV developed in 30% in the PBSC group, 20% in the recipients of bone marrow and 18% in the CD34 group. The corresponding figures for chronic GVHD were 59%, 85% and 0% (P < 0.01) in the three groups, respectively. The probability of non-relapse death was 27% in the recipients of PBSC, 21% in the bone marrow controls and 60% in the CD34 group (NS). The 2-year leukaemia-free survival was 46% in the PBSC group, 41% in the bone marrow group and 25% in the CD34 group (NS).


Subject(s)
Blood Platelets/pathology , Bone Marrow Transplantation , Hematopoietic Stem Cell Transplantation , Neutrophils/pathology , Adolescent , Adult , Child , Child, Preschool , Disease-Free Survival , Graft Survival , HLA Antigens , Humans , Leukemia/blood , Leukemia/immunology , Leukemia/therapy , Middle Aged , Time Factors , Transplantation, Homologous
14.
Blood ; 94(2): 455-64, 1999 Jul 15.
Article in English | MEDLINE | ID: mdl-10397713

ABSTRACT

Peripheral blood stem cell (PBSC) transplants from HLA-A, -B, and -DR compatible unrelated donors (n = 45) were compared with bone marrow (BM; BM group, n = 45). Eighteen patients received CD34-selected PBSC (CD34 group). The PBSCs contained more mononuclear cells, CD34(+), CD3(+), and CD56(+) cells compared with marrow (P <.001). Engraftment was achieved in all 45 patients in the BM group, in 43 of 45 (95%) in the PBSC group, and in 14 of 18 (78%) in the CD34 group (P <.01). In multivariate analysis, a short time to absolute neutrophil count (ANC) equal to 0.5 x 10(9)/L was associated with the PBSC/CD34 groups (P <.001) and granulocyte colony-stimulating factor (G-CSF) treatment (P =.017). A short time to platelets equal to 50 x 10(9)/L was associated with PBSC (P =. 003) and no methotrexate (P =.015). Grades II-IV acute graft-versus-host disease (GVHD) was 20% in the BM controls, 30% in the PBSC group, and 18% in the CD34 group (not significant [NS]). The probability of chronic GVHD was 85% in the BM group, 59% in the PBSC group, and 0% in the CD34 group (P <.01). One-year transplant-related mortality was 21% and 27% and survival was 53% and 54% in the BM and PBSC groups, respectively (NS). The 2-year relapse-free survival was 41% and 46% in the two groups, respectively.


Subject(s)
Bone Marrow Transplantation , Hematopoietic Stem Cell Transplantation , Tissue Donors , Transplantation, Homologous , Adult , Bone Marrow Transplantation/adverse effects , Bone Marrow Transplantation/mortality , Cause of Death , Disease-Free Survival , Female , Graft Survival , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Granulocyte Colony-Stimulating Factor/pharmacology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Incidence , Leukocyte Count , Male , Methotrexate/pharmacology , Middle Aged , Neutrophils , Prospective Studies , Recurrence , Survival Analysis , Transplantation Conditioning , Transplantation, Homologous/adverse effects , Treatment Outcome
15.
Bone Marrow Transplant ; 21 Suppl 3: S81-4, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9712503

ABSTRACT

Twenty-six patients received peripheral blood progenitor cells (PBPC) from unrelated donors at five European Centres. Twenty-five donors were HLA-A, -B and -DR identical and one had a one antigen mismatch. PBPC were mobilised by treatment with G-CSF for 4-5 days. Eleven patients receiving PBPC were compared to 11 patients receiving unrelated bone marrow with comparable prognostic factors. The median mononuclear cell count, the CD3+ cells and the CD56+ cells were seven to 10 times higher in PBPC, compared to bone marrow (P < 0.001). The median CD34+ cell content was 6.1 x 10(6)/kg recipient weight with PBPC, compared to 4.3 with bone marrow (NS). Time from transplantation to neutrophils >0.5 x 10(9)/l was a median of 11 (range 6-21) days using PBPC vs 15 (10-22) days after transplantation of bone marrow (P = 0.03). Transfusions and time to discharge did not differ between the two groups. All 26 patients receiving PBPC engrafted. Acute GVHD grades II-IV was seen in 8/26 (31%) and chronic GVHD in 8/18 (44%). Overall, 13/26 (50%) of the patients are alive and well with a median follow-up of 9 (2-35) months.


Subject(s)
Bone Marrow Transplantation , Graft Survival , Hematopoietic Stem Cell Transplantation , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Histocompatibility Testing , Humans , Transplantation, Homologous , Treatment Outcome
17.
Blood ; 90(12): 4725-35, 1997 Dec 15.
Article in English | MEDLINE | ID: mdl-9389688

ABSTRACT

The clinical results, cellular immune reconstitution, and hematopoietic chimerism obtained after transplantation of recombinant human granulocyte colony-stimulating factor mobilized allogeneic peripheral blood stem cells (PBSCs) from genotypically human leukocyte antigen (HLA)-identical sibling (n = 36) or alternative family donors (n = 24) were prospectively compared in patients with hematologic malignancies. Thirty-two of 34 evaluable patients with HLA-identical sibling donors and all patients with alternative family donors achieved trilineage engraftment. The median time intervals to reach peripheral neutrophil counts <500/microL (13 v 17 days) or <1,000/microL (16 v 19 days) and unsupported platelet counts <20,000/microL (11 v 15 days) or <50, 000/microL (19 v 24 days) as well as red blood cell and platelet transfusion requirements were not significantly different between both patient subsets. The cumulative probability of grades II through IV acute graft-versus-host disease (GVHD) for the 60 study patients was 48% +/- 10% but ranged between 86% +/- 12% in patients whose donors had at least one HLA-A,B,DR,DQ,DP antigen disparity in direction to acute GVHD, and 25% +/- 9% in recipients of GVHD-matched transplants (P < .003). The 2-year survival estimates were 54% +/- 10% for patients with alternative family donors and 65% +/- 9% for patients with HLA-identical sibling donors. Multivariate analysis identified the pretransplantation disease stage, patient age, and acute GVHD as independent predictors of overall and disease-free survival, whereas alternative family donors alone had no adverse effect on these clinical endpoints. Monthly monitoring of peripheral blood T-helper cell subsets, B cells, and monocytes during the first year posttransplantation showed a nearly identical course of immune cell reconstitution in both patient subsets. In addition, no differences in the proportions of complete chimeric patients were detectable between the two patient subsets by sex chromosome and variable number of tandem repeats analysis up to 12 months posttransplantation. In conclusion, PBSCs from alternative family donors represent an attractive source for allogeneic transplantation in patients lacking HLA-identical sibling donors and should be further evaluated in comparison with marrow transplants from alternative family donors.


Subject(s)
Granulocyte Colony-Stimulating Factor/pharmacology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cell Transplantation , Transplantation, Homologous , Adolescent , Adult , Aged , Child , Child, Preschool , Chimera , Female , Filgrastim , Graft vs Host Disease/etiology , Hematologic Neoplasms/immunology , Hematologic Neoplasms/mortality , Histocompatibility Testing , Humans , Male , Middle Aged , Polymerase Chain Reaction , Prospective Studies , Recombinant Proteins , Survival Rate
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