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)

Seventeen patients and their family donors HLA 2 - 3 antigen mismatched of 2 - 3 loci were enrolled in the study of haploidentical transplants from February 1999 to March 2001. Among patients with leukemia, most patients were classified as high risk. Eleven patients with ALL were all in more than second remission but one was in relapse. Patients with AML were one in CR1, one in CR2 while 4 patients with CML were two in CP and two in AP. The male-to-female ratio was 14:3 and the median age was 15 (range from 8 to 35). Conditioning regimens included Ara-C 3.0 g/m(2), 2 times per day x 3 d, on day 7, 6 and 5 pre-transplantation, CTX 45 mg/(kg per d) x 2 d on day 5 and 4 pretransplantation. TBI with 1000 cGy by 2 fractions on day 2 and 1 pretransplantation. The fresh and unmanipulated marrow was infused on day 0. Donors were received G-CSF (Lenograstim) at 3 - 4 microg/(kg per d) x 7 d. The BM cells were collected on eighth day. In GVHD prophylaxis, CSA, MTX, ATG (Antithymocyte globulin, Rabbit Fresenius S) and MMF (mycophenolate mofetic) were used in different periods. The dose of CSA was 1.5 mg/(kg per d) on day 7 to 1 pretransplantation, then 3 mg/(kg per d) from day 1 pretransplantation. MTX was 15 mg/m(2) on day 1 and 10 mg/m(2) on day 3, 6 and 11 posttransplantation. ATG was administered day 4 to 1 pretransplantation at 5 mg/(kg per d) and MMF dose was 1.0 g/d from day 7 posttransplantation. All patients established successful engraftment after initial transplantation. The median days of neutrophil exceeding 0.5 x 10(9)/L and platelet exceeding 20 x 10(9)/L were 18 (range 13 - 23) and 20 (range 16 - 32) days, respectively. Patients were monitored up to day 100 for the sign of aGVHD. The established grades II to IV aGVHD occurred in 5 out of 17 patients (29.4%). Eleven patients were surviving at a median follow-up of 13 months (range 3 - 27 months). Six out of the 17 patients died those 3 of them died of severe aGVHD, 2 of infection and 1 of leukemia relapse. Severe regimen-related toxicities were not experienced in all patients. The median follow-up period was 13 (range 3 - 27) months. Eleven patients were alive in disease-free situation with a Karnofsky performance status of 100%. This could be caused by the low overall incidence of aGVHD as a result of BM primed with G-CSF. The four-agent of immunosuppressive combined prophylaxis against GVHD in different periods may be highly effective.
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PMID:[Successful engraftment of T-cell undepleted haploidentical transplants by donor primed with G-CSF and additional use of ATG and MMF for recipients]. 1251 19

The aim of study was to investigate the pharmacokinetics and distribution of antithymocyte globulin (ATG) in recipients of partially HLA-matched hematopoietic stem cell transplantation. Fifteen patients with hematological disorders were received hematopoietic stem cell transplantation from partially HLA-matched related donor between October 2003 and October 2004 in the Institute of Hematology and People Hospital, Peking University. All patients including 5 cases of AML, 6 cases of CML, 3 cases of ALL, 1 case of AA were consecutively enrolled in the present study after providing written informed consent. Antithymocyte globulin was administered before allogeneic hematopoietic stem cell transplantation at a dose of 2.5 mg/kg daily for 4 consecutive days (total dose of 10 mg/kg) in the conditioning regimen. The concentration of rabbit ATG in the serum of 15 patients was measured using a new enzyme-linked immunoabsorbent assay (ELISA) for the Fc portion of rabbit IgG. The results showed that the washout phase of ATG elimination was analyzed over 0 - 120 days, results were well-fitted by a single exponential decay giving a mean elimination half-life (t(1/2) beta) of 29.67 +/- 2.60 days. A mean value for the apparent volume of distribution of ATG (V) obtained by analysis of data was 0.12 +/- 0.02 L/kg body weight. The serum concentration of ATG increased up to 44.8% at 5 day before transplantation, peak concentration of ATG was 136.0 +/- 10.3 mg/L, its concentration slowly descend at 0 day, fall up to 7.1 +/- 0.06 microg/ml at 90 day after dosing; t(max) 4.8 +/- 0.7 days; According to AIC (Akaike's information criterion), two compartment model of ATG was estimated. It is concluded that the conditioning regimen containing the dosage of 10 mg/kg of ATG is effective and safely in recipients of partially HLA-matched hematopoietic stem cell transplantation. There is no racial difference in the pharmacokinetics of ATG.
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PMID:[Pharmacokinetics of antithymocyte globulin in recipients under-going HLA partially matched hematopoietic stem cell transplantation]. 1749 May 43

Graft failure is associated with a high mortality rate. To date, regimens invoked for second transplants have resulted in inconsistent engraftment with high transplant-related mortality (TRM). We here report 16 consecutive patients, aged 4-59 years, who received second HSCT (HSCT-2) at a median of 45 days following primary or secondary failure of an initial unmodified (N = 3) or T cell-depleted (TCD) (N = 13) HSCT (HSCT-1). HSCT-1 was administered after myeloablative total body irradiation (TBI)- or alkylator-based conditioning for acute leukemias (N = 7), MDS (N = 6), CML (N = 2), and Fanconi anemia (N = 1). All patients experienced 1 or more infectious complications between HSCT-1 and HSCT-2, and 10 patients had active infections at the time of HSCT-2. Cytoreduction regimens used for HSCT-2 included fludarabine (Flu) in combination with cyclophosphamide (CTX) (N = 9), or thiotepa (Thio) (N = 5). In addition, 1 patient received Flu alone and 1 patient Thio combined with CTX. Antithymocyte globulin (ATG) (N = 11) or Alemtuzumab (N = 3) was added pretransplant to prevent rejection. For HSCT-2, donors included HLA-matched (N = 3) or mismatched (N = 8) related, or matched (N = 2) or mismatched (N = 3) unrelated donors. The primary graft donor was used in 6 of 16 cases. The grafts administered were unmodified peripheral blood stem cell transplantation (PBSCT) (N = 5) or bone marrow transplantation (BMT) (N = 3), TCD PBSCT (N = 8). All patients achieved engraftment at a median of 12 days and evaluable patients achieved complete donor chimerism. Six patients are alive with a median follow-up of 49 months, including 4/9 conditioned with Flu/CTX. In this series, outcome was statistically superior for younger patients (<or=20 years). In summary, second HSCT using the combination of a fludarabine- and ATG-based, nonmyeloablative regimen and higher numbers of CD34+ progenitor cells has been associated with acceptable toxicity and allowed consistent engraftment with hematopoietic reconstitution in patients with previous graft failure.
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PMID:Fludarabine-based conditioning secures engraftment of second hematopoietic stem cell allografts (HSCT) in the treatment of initial graft failure. 1795 Sep 18