Disease relevance of Myleran

• Survival of patients with polycythemia vera on busulfan or 32P [1].
• Fifty-one patients with acute nonlymphocytic leukemia (16 with end-stage disease, 17 in second or third remission or in early relapse, and 18 in first remission) were given infusions of HLA-identical sibling marrow after cytoreduction with high doses of busulfan and cyclophosphamide [2].
• Endocardial fibrosis following busulfan treatment [3].
• Sicca syndrome in a patient with toxic reaction to busulfan [4].
• Effect of busulfan on oncornavirus-like activity in platelets and chromosomes in polycythemia vera and essential thrombocythemia [5].

Psychiatry related information on Myleran

• PURPOSE: In an attempt to intensify conditioning therapy for bone marrow transplantation of hematologic malignancies, a retrospective three center evaluation of escalating doses of etoposide added to cyclophosphamide and either total body irradiation or busulfan was undertaken [6].
• The time response was investigated by examining bone-marrow samples 1, 2, 4 or 10 days after i.p. injection of 40 mg of Myleran [7].

High impact information on Myleran

• We conclude that high-dose chemotherapy with busulfan and cyclophosphamide, followed by allogeneic-marrow transplantation, can produce long-term remission of acute leukemia [2].
• Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide [2].
• The effect of busulfan therapy on the activity of oncornavirus-like particles and chromosome patterns in patients with polycythemia vera and essential thrombocythemia was studied [5].
• Mice treated with BU and EP and having HT-induced polycythemia were inoculated with the polycythemia-inducing strain of Friend virus (FVP) and determinations were made for the presence of tumor colony-forming units (tCFU) [8].
• Furthermore, the increased numbers of this FVP target cell in the EP-stimulated, BU-treated mice with HT-induced polycythemia supported the model licating the target for this effect in the EP-responsive cell population [8].

Chemical compound and disease context of Myleran

• 5 patients receiving continuous busulphan and 6-thioguanine for chronic myeloid leukaemia (CML) were found to have oesophageal varices associated with abnormal liver function tests [9].
• Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group [10].
• NST based on the use of fludarabine, low-dose busulfan, and anti-T-lymphocyte globulin (ATG) was employed in 24 patients aged 3 to 63 years with chronic myeloid leukemia (CML) in first chronic phase (CP) [11].
• Forty patients with multiple myeloma received thiotepa (750 mg/m2), busulfan (10 mg/kg), and cyclophosphamide (120 mg/kg) (TBC) followed by autologous bone marrow or blood stem cell support [12].
• Acute graft-versus-host disease prophylaxis with methotrexate and cyclosporine after busulfan and cyclophosphamide in patients with hematologic malignancies [13].

Biological context of Myleran

• Busulfan pharmacokinetics using a single daily high-dose regimen in children with acute leukemia [14].
• Dose (milligrams per kilogram), peak plasma level, and area under the curve (AUC) were all higher in 12 children treated with 150 mg/m2 busulfan than in 9 children treated with 4 mg/kg [14].
• We applied a well-tolerated, nonirradiation-based, allogeneic transplantation protocol using nonmyeloablative preconditioning (low-dose busulfan) and costimulation blockade (CTLA4-Ig and anti-CD40L) to produce mixed chimerism and transplantation tolerance to fully major histocompatibility complex-mismatched donor marrow [15].
• Once engraftment occurred, whether patients had or had not received Busulfan in the conditioning regimen did not influence the kinetics and quality of T-cell function development [16].
• A complete cytogenetic response was induced in seven (8.8%) of 80 patients treated with IFN-alpha and two (2.5%) of 79 patients treated with busulfan, and a partial cytogenetic response was 7.5% (6/80) and 2.5% (2/79), respectively [17].

Anatomical context of Myleran

• A single injection of Myleran reduced the pluripotent hematopoietic stem cell, i.e., colony forming unit(s) (CFU), and the erythropoietin-responsive cell (ERC) in polycythemic mice to around 0.5% that of the controls [18].
• After high-dose chemotherapy in 14 of the patients (busulphan and cyclophosphamide), these cells were used to augment autologous bone-marrow rescue and post-transplant filgrastim treatment [19].
• To test this possibility 587 patients with CML in chronic phase were randomly allocated to receive lymphoblastoid cell-line interferon-alpha n1 (IFN-alpha, n = 293) or chemotherapy with busulphan or hydroxyurea (no IFN-alpha, n = 294) as maintenance after initial induction treatment with cytotoxic drugs [20].
• The rate of decrease of the elevated leukocyte count was more rapid with DBM, but prolonged disease control off treatment occurred in only three of 14 cases as opposed to nine of fifteen busulfan-treated patients who required a median delay of 12 mo before maintenance could be initiated [21].
• Despite slower early reconstitution after lower doses of busulfan, donor lymphocytes exceeded 90% to 95% by 90 to 120 days after HCT in all mice given at least 20 mg/kg [22].

Associations of Myleran with other chemical compounds

• Clobazam for seizure prophylaxis during busulfan chemotherapy [23].
• We, the European Working Group on Childhood MDS (EWOG-MDS) and the European Blood and Marrow Transplantation (EBMT) Group, report the outcome of 100 children (67 boys and 33 girls) with JMML given unmanipulated HSCT after a preparative regimen including busulfan, cyclophosphamide, and melphalan [24].
• The first 21 patients received busulfan 8 mg/kg, fludarabine 200 mg/m2, and 200 cGy of total body irradiation (Bu/Flu/TBI) [25].
• The effects of pretransplant conditioning with high-dose busulfan, a myeloablative but nonimmunosuppressive alkylating agent, on reconstitution of lymphoid tissues by donor cells after bone marrow transplantation (BMT) has not been extensively examined [22].
• Erythroid progenitors (B-8, B-4, CFU-e) in the femoral marrow of polycythemic mice were measured by in vitro culture assays after a single administration of BCNU or Myleran [26].

Gene context of Myleran

• We conclude that GSTA1-1 is the major isoform catalyzing busulfan conjugation, whereas GSTM1-1 and GSTP1-1 may be important in the protection of specific cells [27].
• We conclude that the GSTM1-null genotype predisposes to HVOD, and the sinusoidal endothelial cells and hepatocyte damage may be mediated by metabolites of busulfan through depletion of the cellular GSH pool [28].
• Hematopoietic cell transplantation in the twitcher mouse. The effects of pretransplant conditioning with graded doses of busulfan [29].
• After cryptorchidism or busulfan treatment, mEP17 levels were either greatly diminished or not detected [30].
• Three and four weeks after busulfan treatment, RAD51 and FasL expression decreased to nearly undetectable levels, indicating that meiotic spermatocytes and post-meiotic cells, respectively, were lost [31].

Analytical, diagnostic and therapeutic context of Myleran

• Splenectomy during chronic-phase chronic myeloid leukemia permits easier control of the disease in patients who are thrombocytopenic due to busulfan toxicity or sensitivity [32].
• In addition, for patients with CML receiving 0.2 x 10(6)/kg or less CD3(+) cells, total body irradiation might be better than busulphan-based regimens [33].
• Most transplant recipients were children (n = 25), received a myeloablative busulphan-based regimen (n = 23), and had unmodified marrow allografts (n = 23) from human leukocyte antigen (HLA)-identical sibling donors (n = 25) [34].
• Therapeutic drug monitoring of busulfan and pharmacokinetic dose adjustments appear to be useful in reducing the incidence of VOD in patients receiving this agent [35].
• Exposure to P32, busulphan, and pipobroman (HR, 5.46; 95% CI, 1.84-16.25; P = .0023), but not to hydroxyurea (HU) alone (HR, 0.86; 95% CI, 0.26-2.88; P = .8021), had an independent role in producing an excess risk for progression to AML/MDS compared with treatment with phlebotomy or interferon [36].

References