Allogeneic bone marrow transplantation versus chemotherapy for childhood acute lymphoblastic leukemia in second remission: an update.
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Adolescent↗
Biomedical subjects
M T van Lint
Publications and source records attributed to M T van Lint.
The effect of total body irradiation dose and chronic graft-versus-host disease on leukaemic relapse after allogeneic bone marrow transplantation.
One-hundred and five patients undergoing allogeneic bone marrow transplantation (BMT) for acute myeloid leukaemia (AML) (n = 61) and chronic myeloid leukaemia (n = 44) were analysed for risk factors associated with relapse. All patients received marrow from an HLA identical sibling after preparation with cyclophosphamide 120 mg/kg and total body irradiation (TBI) 330 cGy on each of the three days prior to transplantation. There was a difference of +/- 18% between the nominal total dose of 990 cGy and the actual dose received as indicated by dosimetric recordings. While interstitial pneumonitis had minimal impact on survival (4%) there was a considerable difference in the incidence of relapses. The incidence of relapse was 55% versus 11% in patients receiving less or more than 990 cGy respectively and this had a major impact on survival (38% v. 74% at 7 years) since transplant-related mortality was comparable in the two groups. A multivariate Cox analysis indicated that a lower TBI dose (less than 990 cGy) was the most significant factor associated with relapse and the second most important factor associated with recurrence of leukaemia was the absence of chronic graft-versus-host-disease (cGvHD). Actuarial relapse incidence was 62%. 28% and 18% for patients with no, limited or extensive chronic GvHD respectively. However, chronic GVHD had no significant impact on survival. Combined stratification for TBI dose and cGvHD showed that the dose effect of TBI on relapse was evident both in patients with and without cGvHD. Chronic GvHD influenced the risk of relapse only in patients receiving less than 990 cGy. These results suggest that a higher dose of TBI, within this schedule, produced long-term disease-free survival in the majority of AMLs and CMLs. Minor radiobiological side effects were experienced but a small reduction of the dose may significantly increase the risk of relapse.
Adolescent↗
Bone marrow transplantation for secondary (therapy-related) acute non-lymphoblastic leukaemia: report of a case associated with adoptive beta-thalassaemia.
A female patient with therapy-related acute non-lymphoblastic leukaemia occurring after intensive combined modality treatment for IIIB Hodgkin's disease was transplanted from her HLA-identical brother. No attempt was made to induce a remission and the transplant was performed with standard chemoradiotherapeutic conditioning. Three years after the transplant the patient is alive in complete remission with a 46,XY karyotype. The donor has a mild, heterozygous beta-thalassaemia ('thalassaemia minima'). The recipient has much more pronounced thalassaemic features, similar to so-called thalassaemia intermedia, with peripheral blood smears indistinguishable from thalassaemia major. The erythrocytic alterations are undoubtedly due to the splenectomy which was performed during a staging procedure, but the marked difference between donor and recipient haemoglobin values cannot be attributed solely to the asplenic state.
Bone Marrow Transplantation↗
Bone marrow transplantation in multiple myeloma: report from the European Cooperative Group for Bone Marrow Transplantation.
Of 14 patients who received an allogeneic bone marrow graft from HLA-compatible sibling donors, 10 have survived for 6 to 34 months posttransplantation (median, 12 months). Four patients have died, two of relapse at extramedullary sites, one of severe acute GVHD, and one from GI bleeding and pericardial effusion. One patient is alive in relapse and four patients have signs of minimal persistent disease. Five patients are well without signs of active disease. Minor improvement in osteolytic lesions on X-ray were seen in three patients, but the X-ray bone structure was mainly unchanged in most patients. Bone marrow transplantation appears promising for treatment of certain patients with multiple myeloma.
Adult↗
Intravenous monoclonal antibody (BT 5/9) for the treatment of acute graft-versus-host disease.
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Adolescent↗
Cyclosporin A in marrow transplantation for leukemia and aplastic anemia.
A total of 29 consecutive patients with leukemia or aplastic anemia who received an HLA-identical marrow graft were given cyclosporin A (CyA) to prevent graft-versus-host disease (GvHD). These patients were compared with an historic group of 25 similar patients with leukemia or AA given methotrexate (MTX) for GvHD prophylaxis at this institution. Engraftment was faster in patients given CyA when compared with MTX patients, with less days of granulocytopenia (P = 0.04), a shorter interval before reaching a platelet count of 70 X 10(9)/l (P = 0.04), fewer major infections (P = 0.01), and fewer days on intravenous antibiotics (P = 0.02). There were no graft failures in CyA patients compared with four of 25 in MTX patients (P = 0.01). Early mortality was lower in CyA patients but not significantly (P = 0.06). The incidence of pulmonary complications was comparable, five of 29 and seven of 25 in CyA and MTX patients, respectively, but the clinical features of such complications differed. Interstitial pneumonia developing after day 30 was seen in MTX patients, whereas an acute respiratory distress syndrome developing between day +8 and day +18 was seen in CyA patients. Acute GvHD was less severe in CyA patients (P = 0.04), but chronic GvHD was comparable (P = 0.3). The actual one-year survival is currently 72% and 52% in CyA and MTX patients, respectively (P = 0.1). Although our initial experience with CyA is encouraging with regard to engraftment and acute GvHD, optimization of CyA protocols will probably be needed for it to be proven as having a definite advantage over MTX.
Adolescent↗
High dose bolus methylprednisolone for the treatment of acute graft versus host disease.
Nineteen patients with acute graft versus host disease (GvHD) following bone marrow transplantation (BMT) were treated with high dose bolus 6-methylprednisolone (BMPr), at the dose of 20 mg/kg/day i.v. for the first 3 days, 10 mg/kg/day i.v. for the following 4 days, and then at doses gradually tapered down to 1 mg/kg/day. All patients except one, who was given preventive BMPr 5 mg/kg/day i.v. on alternate days, were placed on preventive methotrexate therapy after BMT. Sixteen patients were grafted with an HLA matched, and three patients with an HLA mismatched marrow. Overall complete response rate in the HLA matched group was 43%, with an additional 50% showing a partial response. In the HLA mismatched group there were no responses and all three patients proved refractory to BMPr. With respect to organ involvement the complete and partial response rates were respectively 50% and 33% in the skin, 36% and 28% in the liver, 18% and 55% in the gut. Six of sixteen patients in the HLA matched group and none of the three in the HLA mismatched group are surviving. Thirteen patients died: nine patients for causes directly or indirectly related to GvHD, four of other causes (relapse, rejection, hemorrhage and idiopathic interstitial pneumonia). Side effects of BMPr consisted in hyperglicemia, and steroid associated gastritis in 2/3 of the patients, both of which responded well to conventional treatment. This study indicates that high dose BMPr is an effective form of treatment for established acute GvHD, and has no major side effects. The efficacy of BMPr is less clear in recipients of HLA mismatched grafts.
Adolescent↗
GM-CFC growth in chronic granulocytic leukaemia is not affected by a soluble inhibitor released by aplastic anaemia T-cells or mitogen-primed normal T-lymphocytes.
Peripheral blood (PB) and bone marrow (BM) cells were obtained from 12 patients with chronic granulocytic leukaemia (CGL) and cultured in agar for granulocyte macrophage colony formation (GM-CFC). In addition PB and BM CGL cells were co-cultured with T-lymphocytes from patients with immune severe aplastic anaemia (SAA), or with T-cells from healthy donors primed with pokeweed mitogen (PWM). The supernatants of SAA and PWM primed T-cells were also added to CGL cells grown in agar. Normal marrow cells obtained from eight healthy donors were used to set up control cultures and co-cultures. The results of this study indicate that, firstly, T-cells derived from SAA patients and their supernatants suppress GM-CFC growth of normal marrow cells but not of PB nor BM CGL cells, and, secondly, normal T-cells primed with PWM and their supernatants suppress normal marrow GM-CFC but not colony formation of BM nor PB CGL cells. These results provide further evidence that mediators which are effective in regulating normal myeloid progenitor cells fail to inhibit the in vitro growth of GM-CFC from CGL patients.
Adult↗
Generation of CFUC suppressor T cells in vitro. II. Effect of PHA, PWM, and Con-A on bone marrow and peripheral blood lymphocytes from healthy donors.
T lymphocytes were derived by E-rosetting techniques from the peripheral blood and bone marrow of 12 healthy donors. Following incubation of 18 h with PWM, PHA, Con-A or culture medium (RPMI) alone, the lymphocytes were harvested by centrifugation and washed. Both lymphocytes and culture supernatants were tested for CFUC suppressor activity in semisolid bone marrow cultures. The results of this study indicate that (a) T cells and supernatants from unstimulated cultures contained no CFUC suppressor activity, (b) T cells and supernatants from cultures stimulated with PHA, PWM or Con-A significantly suppressed autologous and allogeneic bone marrow CFUC, (c) there was no significant difference between the ability of bone marrow or peripheral blood T cells to inhibit CFUC, and (d) mitogens alone had either no effect or a moderate enhancing activity on marrow CFUC. These findings suggest that generation of CFUC suppressor T cells occurs normally within a few hours of polyclonal T cell stimulation.
Bone Marrow Cells↗
T cell subpopulations after allogeneic bone marrow transplantation.
T-cell subpopulations were studied in six patients after allogeneic bone marrow transplantation for aplastic anemia and acute leukaemia, by means of receptors for IgG (TG-cells) and IgM (TM-cells). Significant modifications of TM-TG levels were found: a 2 to 10 fold increase of TG cells and a 2 to 10 fold decrease of TM cells from pre-transplant levels could be observed. The TM-TG imbalance appeared together with the clinical signs of GVHD: the level of TM-depression (but not the level of TG increase) correlated with the severity of GVHD. The TM-TG modifications were observed as long as 3 years after transplantation, also in the absence of signs of GVHD. In addition, all six patients were found to have severely impaired pokeweed-induced B-cell differentiation. The clinical implications and the possible lack of T-helper activity are discussed.
Acute Disease↗
Lymphoid antigens on blast cells in the agranular metamorphosis of chronic myelogenous leukaemia.
Undifferentiated blasts from a Ph'-positive chronic myelogenous leukaemia (CML) in terminal metamorphosis were reacted in an indirect immunofluorescence test with antilymphocytic globulins (AHLGs), raised against cultured lymphoblasts, thoracic duct and peripheral blood lymphocytes from healthy donors. After proper myeloid and/or monocytic absorptions the AHLGs interacted strongly with the undifferentiated blasts of CML, while this was not true for parallel controls with non-lymphoid leukaemias, both acute and chronic. The intensity of fluorescence, as determined by the use of a microfluorimeter, on these agranular blasts was comparable to the positivity of lymphoid cells from acute and chonic lymphatic leukaemias. These findings lend further support to the conception of a lymphoblast-like variety of terminal blastic crisis in chronic myelogenous leukaemia.
Antigens, Surface↗
Cytogenetic abnormalities in patients with severe aplastic anemia.
BACKGROUND: Cytogenetic abnormalities have been described in a few patients with otherwise typical severe aplastic anemia (SAA), and the possible clonal nature of this disease is a controversial issue. MATERIALS AND METHODS: Sixty-nine patients with acquired severe aplastic anemia underwent cytogenetic examination on bone marrow cells at the time of diagnosis (n = 34) and/or at least twice after immunosuppressive therapy (IS) (n = 35). RESULTS: We identified 2 major groups. Group A: 51 patients (74%) were normal and remained normal. Group B: 18 patients (26%) had at least one abnormal cytogenetic analysis. This second group could be further subdivided as follows: (B1) chromosomal abnormalities not present at first examination and acquired in the course of the disease (n = 7); (B2) clonal cytogenetic abnormalities present at first examination and persisting (n = 3); (B3) reversible cytogenetic abnormalities (n = 8). The most frequent abnormality was trisomy 8 (n = 8) followed by monosomy 7 (n = 2); 82% of patients are alive in group A and 61% in group B. Three patients developed acute leukemia, all from group B. This represents 4% of all patients or 17% of those with at least one abnormal cytogenetic test. CONCLUSIONS: Thus the majority of SAA patients have normal karyotypes in marrow cells at presentation and at follow-up. Patients with abnormal karyotypes exist and can be further subdivided into those with reversible and those with persistent abnormalities. The latter are at risk of developing myelodysplasia or acute leukemia.
Adolescent↗