Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between 1995 and 1997 twenty two patients with different hematological diseases ( CML n=10, AML n=6, ALL n=l, NHL n=3, SAA n=1,solid tumor n=1 ) and a median age of 37 (range, 20 to 55) years received unmanipulated peripheral blood stem cell (PBSC) transplants from HLA-identical sibling donors at our institution. Myeloablative chemotherapy consisted of cyclophosphamide (CY) and total body irradiation in 11, and chemotherapy alone in 11 patients. For graft-versus host-disease (GVHD) prophylaxis all patients were given cyclosporine A and methotrexate according to the Seattle protocol. PBSC were mobilized by granulocyte colony-stimulating factor (G-CSF) given at 10 microg/kg body weight (b.w.)/day for four days. Harvest of PBSC was started on day 5 and continued on day 6 if necessary. A median of 1 leukapheresis (range, 1 to 2) was performed and a median of 5.7 x 10(6) CD34+cells/kg b.w. (1.34 to 21.5) were obtained. Ten patients received G-CSF (5 microg/kg b.w.) starting on day one after PBSCT until neutrophil recovery. Absolute neutrophil counts >0.5 x 10(9)/L and ANC >1.0 x 10(9)/L were reached after a median of 13 (range 8 to 18) and 15 (range 9 to 19) days after PBSCT. Unsupported platelet counts >20 x 10(9)/L and 50 x 10(9)/L were reached after 17 (range 8 to 32) and 22 (range 13 to 40) days after PBSCT, respectively. Incidence of acute GVHD grade I to IV was 52%, extensive chronic GVHD occurred in 25% of patients. After a median observation time of 11 (range, 3 to 34) months twelve patients (55%) are alive and well. In summary, infusion of allogeneic PBSC after myeloablative therapy allows rapid and sustained hematologic reconstitution. Incidence of acute GVHD is not increased, for assessment of chronic GVHD longer observation times and larger patient numbers are required.
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PMID:Experience with allogeneic and syngeneic blood stem cell transplantation in patients with hematological malignancies. 991 35

Among 290 BMT procedures: 74 AML, 78 ALL, 34 CML, 6 SAA, 3 MDS, 42 HD, 35 NHL, 11 MM, and 7 solid tumours (breast or testis cancer) Allogeneic BMT was performed in 76 patients and ABMT/APBCT in 214 patients. Survival, DFS and relapse curves were calculated using the Kaplan-Meier product limit method. Variables potentially affecting survival and DFS were assessed in a multivariate analysis by the Cox proportional hazard model in a stepwise regression. The promising results were obtained in high risk adult ALL in the first CR. DFS in CR1 patients transplanted after full dose induction and high dose consolidation was significantly longer if compared to those who received dose/time reduced or postponed treatment. For CR> or =2 patients and with CNS involvement at diagnosis ABMT offers a salvage therapy that needs further improvement. In relapsed and refractory HD better results are obtained in patients relapsing > 1 year after first CR and in patients with entirely nodal localisation of this relapse. In NHL bone marrow and spleen infiltration at diagnosis appear to be an unfavourable prognostic factor.
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PMID:Allogeneic and autologous bone marrow transplantation in single centre experience. 991 50

Data on 73,070 patients for seven major haematological malignancies diagnosed in Europe between 1985 and 1989 from 39 population-based cancer registries in 17 countries are included in the EUROCARE database. Relative survival was analysed by country and age between 1985 and 1989 and time trends were analysed from 1978-1989 for 13 countries which collaborated in EUROCARE for this entire period. The European weighted age-standardised 5-year relative survival rate was 72% for patients with Hodgkin's disease (HD, ranging from 45 to 76% in 13 countries), 63% for chronic lymphocytic leukaemia (CLL, range 51-79%, 14 countries), 46% for patients with non-Hodgkin's lymphoma (NHL, range 25-63%, 17 countries), 31% for patients with chronic myelocytic leukaemia (CML, range 8-40%, 13 countries), 28% for patients with multiple myeloma (MM, range 18-36%, 14 countries), 25% for patients with acute lymphoblastic leukaemia (ALL, range 19-33%, 7 countries) and 10% for patients with acute myeloblastic leukaemia (AML, range 4-15%, 11 countries). In all countries, relative survival declined with age, most markedly for patients with acute leukaemias. Patients in Northern and Western Europe had better survival rates, particularly in younger patients (15-45 years of age), whilst those in Eastern European countries tended to have poorer rates. Compared with 1978-1979, relative 5-year survival improved in 1987-1989 for most haematological malignancies (relative risk (RR) of death for CLL 0.65, AML 0.75, HD 0.76, ALL 0.79, NHL 0.82), with only CML (RR 0.95) and MM (RR 1.00) showing little or no change. These results suggest that generally and particularly in Eastern Europe there is room for improvement in the diagnosis and treatment of haematological malignancies. The intercountry differences also highlight the importance of socio-economic conditions to health status.
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PMID:Variation in survival of adult patients with haematological malignancies in Europe since 1978. EUROCARE Working Group. 1007 Feb 96

To circumvent aGVHD in the early phase after allogeneic stem cell transplantation but to provide GVL activity later on, we performed alloPBSCT with CD34+ selected grafts followed by delayed add-back of CD3+ T cells. Ten consecutive patients having an HLA-identical sibling donor were enrolled on to this trial. Four patients were in first CR of high-risk ALL, another four in first CR of AML, one was in second myeloid blast crisis of CML, and one was in PR of relapsed NHL. Conditioning consisted of 2 x 60 mg/kg CY plus 12 Gy TBI. G-CSF (Filgrastim) mobilized peripheral cells were CD34+ selected using the Isolex 300i system in nine patients and the CliniMacs system in one. Median CD34+ purity was 86%. A median of 2.8 x 10(6)/kg CD34+ cells were transplanted. The number of CD3+ cells in the allografts was 5.7 x 10(4)/kg (median) after Isolex 300i, and 0.2 x 10(4)/kg after CliniMacs. All patients received G-CSF (Filgrastim) and engrafted rapidly. Standard-dose CsA was administered, and until day +60 no aGVHD occurred. At that time point, seven patients received 2 x 10(6)/kg CD3+ cells while CsA had been tapered to 50% of the starting dose. One of these patients died after a second T cell boost given on day +90 without concomitant immunosuppression due to grade IV intestinal aGVHD. Three others developed cutaneous cGVHD. Taken together, T cell depletion by CD34+ selection does not impair rapid engraftment in the HLA-identical sibling donor setting. Using standard-dose CsA the risk for acute GVHD seems to be minimized. Add-back of 2 x 10(6)/kg CD3+ cells on day +60 with CsA protection is feasible. However, whether this is the optimal time point and number of T cells remain to be further elucidated.
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PMID:CD34 selected alloPBSCT and adoptive immunotherapy. 1093 76

Peripheral blood stem cell transplants (PBSCT) from unrelated donors (n = 37) were compared with bone marrow transplants (BM, bone marrow group, n = 37) in a matched pair analysis. Ten patients (2, class 1) in the alloPBSCT group and seven patients (2, class 1) in the BM group had one HLA locus mismatch donor, respectively. The following factors were matched: HLA-compatibility, diagnosis, disease stage, age and gender. The median age in the PBSC group was 37 years (19-56, excluding one 6-year-old child) and in the BM group 37 years (18-53). The BM group consisted of 12 females and 25 males, 17 females and 20 males were in the PBSC group. Twelve patients in the BM and 11 patients in the PBSC group were diagnosed with AMI,; 7/7, ALL; 15/15, CML; 2/3, MDS; 1/1, NHL. Thirty-four (14/20) of the 74 patients (45%) were considered as high risk patients. The conditioning regimen was BU/CY for standard risk patients with myeloid diseases (31 patients) and TBI/CY for ALL and NHL patients (36 patients); six patients received intensified conditioning with VP16 (2 patients), thiotepa (2 patients) or melphalan (1 patient). The GVHD prophylaxis regimen was used according to the Seattle protocol. DFS was 51% (19 patients) with a median of 352 days and 59% (21 patients) with a median of 760 days, in PBSC and BM transplants, respectively. The median time to leukocyte engraftment in PBSC patients was 14 days (range 6-26 days) and in the BM group 19 days (range 9-29 days; P < 0.02). The time of platelet engraftment did not differ significantly between the groups. The incidence of grade II-IV acute GVHD was 40% (four patients died, 13%) in the PBSC group and 20)% (three patients died, 8%) in the BM group, respectively (P < 0.05, log-rank). No signs of aGVHD were found in 19% of the patients in the PBSC and 27% in the BM group. Our results indicate that allogeneic PBSCT does lead to a significantly faster leukocyte engraftment. The significant increase with regard to the incidence and shorter time of onset of severe aGVHD in PBSC patients, compared to marrow transplant patients, need to be confirmed in a randomised trial.
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PMID:A comparative study of peripheral blood stem cell vs bone marrow transplantation from unrelated donors (MUD): a single center study. 1093 83

This study retrospectively analyses the experience with an intensive enteral feeding protocol in children undergoing BMT at the National Paediatric BMT Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin. Fifty-three patients were transplanted between January 1996 and December 1998; 42 patients received allogeneic transplants, (19 unrelated) and 11 were autologous. Indications included ALL (21), ANLL (3), CML (3), JCML (1), MPS (5), WAS (2), AA/FA (6), NHL/HD (3) and solid tumours (9). Nasogastric (NG) tubes were inserted electively either during conditioning or within the first week when voluntary oral intake had decreased. Nineteen patients were commenced on a whole protein-based formula, 28 on a semi-elemental preparation and two were commenced on an elemental feed. All were maintained on an elemental formula during the period of maximal gut toxicity. Tubes which were vomited were promptly replaced and morphine infusions were routinely employed until mucositis had resolved. Of 49 evaluable patients, 42 (86%) were maintained exclusively on enteral nutrition and seven required parenteral nutrition. Seven patients weighed <85% ideal body weight (IBW) at discharge (range 75-84), only one of whom was <85% IBW at 3 months. Twenty-two patients continued on NG feeds following discharge (median 41 days). No patient had veno-occlusive disease. The programme was overwhelmingly endorsed by patients and/or parents but required intensive multidisciplinary counselling to ensure success.
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PMID:Intensive enteral nutrition support in paediatric bone marrow transplantation. 1136 Jan 15

CD34+ cell counts in peripheral blood (PB) and corresponding numbers of CD34+ cells and colony-forming units-granulocyte/macrophage (CFU-GM) in 299 leukapheresis products of 209 patients undergoing PB progenitor cell (PBPC) mobilization for autologous transplantation in two different centers were analyzed and compared according to diagnosis: non-Hodgkin lymphoma (NHL, 94 leukaphereses), multiple myeloma (MM, 75), Hodgkin's disease (HD, 37), solid tumors (35), and chronic myeloid leukemia (CML, 32). Without separating disease entities, correlations between PB CD34+ cell counts and leukapheresis content of CD34+ cells (r>0.83, P<0.01) and CFU-GM (r>0.81, P<0.01) were excellent. In both centers, a PB CD34 threshold ensuring a leukapheresis yield > 10(6) CD34/kg was determined. This threshold was higher in center 1 than in center 2, and its predictive accuracy (91.4%, i.e., prediction correct 91.4% of the time) was significantly lower than in center 2 (98.4%, P=0.02). When data were analyzed by pathology, PB CD34+ cell counts and leukapheresis content of CD34+ cells and CFU-GM remained well correlated, and in both centers PB CD34 thresholds predictive of a yield > 10(6) CD34/kg per leukapheresis could be determined for each pathology. For most patients, pathology-specific PB CD34 thresholds could be obtained directly from the equation of the PB CD34/leukapheresis CD34 correlation curve; they varied depending on both pathology and center (range: 7-20 x 10(6) CD34/l). Pathology-specific thresholds predicted a leukapheresis yield > or = 10(6) CD34/kg accurately 100% of the time for MM patients in center 2 and HD and solid tumor patients of both centers, resulting in overall rates of accurate prediction of sufficient graft CD34 content of 96.6% in center 1 and 98.9% in center 2.
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PMID:Use of pathology-specific peripheral blood CD34 thresholds to predict leukapheresis CD34 content with optimal accuracy: a bicentric analysis of 299 leukaphereses. 1175 22

Using red cell phenotyping (RCP) and/or cytogenetics (CYT) we identified 19 patients with persisting mixed chimerism (MC) among 231 patients transplanted with partially T cell-depleted stem cell grafts from HLA-identical siblings. Persisting MC is defined as MC for more than 2 years in patients without any evidence of relapse. Median leukemia-free survival in these patients was 150 (range, 50-218) months. Diagnoses were ALL (n= 10); AML (n = 2); CML (n = 2); NHL (n = 2); MDS (n= 1); MM (n = 1) and SAA (n = 1). Purpose of this study was the long-term follow-up of MC and definition of patterns of chimerism in the various subsets of PBMCs and granulocytes. Using a PCR-STR technique CD3(+)/CD4(+) (T4 lymphocytes), CD3(+)/CD8(+) (T8 lymphocytes), CD45(+)/CD19(+) (B lymphocytes), CD45(+)/CD14(+) (monocytes), CD45(+)/CD15(+) (granulocytes) and CD3(-)/CD56(+) (NK-cells) were analyzed. The majority of patients with persisting MC were conditioned with a less intensive conditioning regimen and had little GVHD. Sequential monitoring of the chimerism resulted in a group of patients (n = 7) with very slow transient mixed chimerism that resulted in complete DC after median 7 years. Another nine patients had a relatively high percentage of persisting autologous cells for a median of 12 years and in three patients we observed a stable low percentage of autologous cells. Only two out of 19 patients (AML-CR1, CML-CP1) relapsed during follow-up. Both patients had a relatively high percentage of autologous cells. Chimerism in granulocytes and PBMC subsets was analyzed at a median of 8 years after SCT in nine patients. In five patients mixed chimerism simultaneously detected by RCP and CYT was associated with MC in all subsets. Within each individual patient the percentages of donor and recipient cells were very different between the different subsets. Two CML-CP1 patients were mixed chimera in only two subsets and in one patient these subsets represented pending relapse. In another two patients mixed chimerism with a very low number of autologous red cells was not found in the PBMCs because of the different sensitivity level of the RCP and the PCR-STR technique. We conclude that in patients with persisting mixed chimerism after partially T cell-depleted SCT a remarkable number of patients had lymphoid malignancies, the majority of the patients were conditioned with less intensive conditioning regimens and the mixed chimerism was not correlated with relapse. Chimerism in granulocytes and PBMC subsets did show great intra-individual differences in the subsets and these data correlated well with RCP and CYT data with the exception of the NK cells.
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PMID:Long-term follow-up of persisting mixed chimerism after partially T cell-depleted allogeneic stem cell transplantation. 1184 Feb 58

We describe the toxicity and efficacy of donor lymphocyte infusions (DLIs) given to 81 patients (median age, 50 years) after reduced-intensity conditioning (RIC) transplantations performed at 16 centers in the United Kingdom. The diseases treated included non-Hodgkin lymphoma (NHL; n = 29), chronic myeloid leukemia (CML; n = 12), myeloma (n = 11), acute myeloid leukemia (AML; n = 10), and chronic lymphocytic leukemia (CLL; n = 9). Eighty-eight percent received stem cells from sibling donors. The patients received 130 infusions (median, 1; range, 1-4). Indications for DLI were unsatisfactory response/disease progression in 51 patients, mixed chimerism in 18, preemptive in 10, and other in 2. Graft hypoplasia was uncommon (11%). Grade II to IV graft-versus-host disease (GVHD) occurred in 23 of 81 patients (28%) and limited and extensive chronic GVHD in 5 of 69 and 18 of 69 evaluable patients (total incidence 33%). Conversion from mixed to full donor chimerism occurred in 19 of 55 evaluable patients (35%) at a median of 48 days after the DLI; partial responses occurred in 6 patients (total response rate 45%). Eighteen of 51 (35%) patients with measurable disease after stem cell transplantation had a complete response (2 molecular), and 5 a partial response (total response rate 45%). Eleven of 17 evaluable complete responders had full donor chimerism. Eight of 13 patients with follicular NHL had complete responses as did 4 of 12 patients with CML. Clinical and chimeric responses correlated strongly with acute and chronic GVHD. Forty-seven patients (58%) survive at a median of 508 days after transplantation (range, 155-1171 days) with a median Karnofsky score of 90. Thirty-four patients (42%) died at a median of 211 days after transplantation with the major causes being progressive disease (26%) and GVHD (9%). Further systematic studies are required to determine the efficacy and optimum use of DLI for patients with each disease treated by nonmyeloablative stem cell transplantation.
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PMID:The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. 1238 6

The concept of utilizing enhanced immunosuppression rather than myeloablative cytotoxic conditioning has allowed the engraftment of allogeneic stem cells from related and unrelated donors with lower early transplant-related mortality (TRM) and morbidity. This approach shifts tumor eradication to the graft-vs-host immune response directed against minor histocompatibility antigens expressed on tumor cells. This is not without risk, as the long-term effects of graft-versus-host disease (GVHD), it's treatment, or resulting complications and immunodeficiency may be life threatening. However, this approach does allow the application of a potentially curative procedure to elderly or medically infirm patients who would not tolerate high-dose conditioning regimens. Section I, by Dr. Sandmaier, describes the current use of nonmyeloablative regimens and matched related or unrelated donors for the treatment of patients with CLL, CML, acute leukemia, MDS, lymphoma, and myeloma. In Section II, Dr. Maloney discusses the use of cytoreductive autologous followed by planned non-myeloablative allografts as treatment for patients with myeloma or NHL. This tandem transplant approach has a lower TRM than conventional high dose allografting. The nonmyeloablative allograft may allow the graft-versus-tumor (GVT) immune response to eradicate the minimal residual disease that causes nearly all patients with low-grade NHL or myeloma to relapse following autologous transplantation. In Section III, Dr. Mackinnon discusses the risks and benefits of T cell depletion strategies to prevent acute GVHD, while retaining GVT activity by planned donor lymphocyte infusions. Finally, in Section IV, Dr. Shizuru discusses the relationship between GVHD and GVT activity. Future studies, employing a greater understanding of these issues and the separation of GVHD from GVT activity by immunization or T cell cloning, may allow nonmyeloablative allogeneic transplantation to be safer and more effective.
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PMID:Non-myeloablative transplantation. 1244 34


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