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Biomedical subjects

W Sizoo

Publications and source records attributed to W Sizoo.

At least 37 records · Page 2Linked to original sources
PubMed1988

Comparison of total nodal irradiation versus combined sequence of mantle irradiation with mechlorethamine, vincristine, procarbazine, and prednisone in clinical stages I and II Hodgkin's disease: experience of the European Organization for Research and Treatment of Cancer.

The H5 study of supradiaphragmatic Hodgkin's disease in clinical stages I-II consisted of two controlled trials adapted to patients considered to have either favorable or unfavorable characteristics, based on prognostic factors identified in two former studies by the European Organization for Research and Treatment of Cancer. Of 494 patients, 257 who were classified as having unfavorable prognosis qualified for the more intensive treatment and consequently were spared a staging laparotomy. They were randomized either to total nodal irradiation (TNI) (132 patients) or to treatment with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternated with mantle irradiation (MOPP X 3-mantle irradiation-MOPP X 3; 3M) (125 patients). In complete responders (96%), the 6-year relapse-free survival was 77% in the TNI arm and 91% in the 3M arm (P = .02). Relapses in the initially involved and irradiated mantle area were less frequent in patients started on MOPP. The 6-year actuarial total survival (TS) (TNI, 82%, and 3M, 89%; P = .05) appeared to favor the 3M arm, but this difference disappeared when patients dying from causes unrelated to cancer were excluded from analysis. In men less than or equal to 40 years old, there was no difference in relapse-free survival, freedom from disease progression, or TS between the groups receiving TNI and 3M. Thus, TNI is a short and appealing treatment, especially because it preserves fertility. The same observation was true in women less than or equal to 40 years old. In addition, even irradiation less than TNI, which is meant to spare the ovaries, provided a TS similar to that for 3M.

Adult↗
PubMed1987

Concentrations of ciclosporin in allogeneic bone marrow recipients. Comparison of assay methods.

Thirteen patients in complete remission from acute nonlymphoblastic leukaemia or in chronic phase of chronic myelocytic leukaemia were treated with total body irradiation, cyclophosphamide and allogeneic bone marrow transplantation (BMT). Ciclosporin (CS) was administered for the prevention and the treatment of Graft versus Host Disease. Blood concentrations of CS were determined by Radioimmunoassay (RIA) and by High Performance Liquid Chromatography (HPLC). Trough levels of CS in peripheral blood as measured by RIA exceeded HPLC derived levels in nearly all (56/58) samples with a ratio of RIA:HPLC ranging from 2.43 +/- 1.42 at day 12 to 3.65 +/- 1.86 at day 26 after BMT (means +/- SD). A comparable ratio was found as regards the peak concentrations of CS in peripheral blood. Neither the dose of CS (0.5-3.0 mg/kg/day intravenously; 3.0-5.0 mg/kg/day per os) nor the duration of treatment (12, 19, 26 or 33 days after start of CS) were a significant factor as regards the ratio between HPLC and RIA. Concentrations of CS were also determined in bone marrow nucleated cells at 1 hour after the drug infusion had started. Here the ratio of RIA versus HPLC varied upon the duration of CS treatment with a highest ratio of 8.75 +/- 8.74 at day 12 after BMT. Bone marrow levels corresponded well with blood trough concentrations (p less than 0.01). It is concluded that the concentrations of CS in blood and bone marrow as determined by RIA and HPLC differ significantly, though consistently. At present, no advantage can be attributed to either method of analysis for routine clinical monitoring, as long as detailed information on the immunosuppressive and the toxic characteristics of CS metabolites in humans is lacking.

Acute Disease↗
PubMed1987

Rapid clearance of cytomegalovirus-specific IgG after repeated intravenous infusions of human immunoglobulin into allogeneic bone marrow transplant recipients.

We studied the kinetics of the disappearance of CMV-specific IgG from the serum of 18 allogeneic bone marrow transplant recipients who were receiving repeated intravenous infusions of immunoglobulin. Peak serum titers occurred 24-48 hr after infusion. The mean half-life of IgG to CMV varied from 30 to 70 hr. Additional studies showed that this unexpectedly short half-life was not specific for either the preparation used or the type of patient studied. Repeated treatment did not prevent patients from developing CMV infections (incidence, 50%); however, none of the patients developed CMV interstitial pneumonitis. Treatment had to be discontinued for one patient because of a serum sickness-like syndrome. Our results suggest that rational, time-sequential passive immunization regimens should be developed.

Antibodies, Viral↗
PubMed1987

Different repopulation kinetics of erythroid (BFU-E), myeloid (CFU-GM) and T lymphocyte (TL-CFU) progenitor cells after autologous and allogeneic bone marrow transplantation.

Marrow recovery of erythroid (BFU-E), myeloid (CFU-GM) and T-lymphocyte (TL-CFU) progenitor cells was studied at various time intervals after autologous bone marrow transplantation in 10 patients with acute myeloid leukaemia in remission. These data were compared with those in 14 recipients of T-cell depleted allogeneic marrow grafts. The results indicate markedly different repopulation kinetics of BFU-E, CFU-GM and TL-CFU after autologous and allogeneic bone marrow transplantation. Following autografting reduced numbers of BFU-E and CFU-GM were always present at 2 months after transplantation. Between 2-6 and 6-24 months a gradual increase occurred, although reduced BFU-E and CFU-GM values were still noted in 50% of the cases in spite of normal bone marrow cellularity and restoration of peripheral blood counts. In contrast, in the allograft recipients normal BFU-E numbers appeared within 2 months after transplantation. In addition, CFU-GM values had become normal in 35% of the tests performed at 1-2 months and respectively in 66% and 100% at 2-6 and 6-24 months. The recovery pattern of TL-CFU differed from that of the other haemopoietic progenitor cells. TL-CFU showed a fast recovery, i.e. within 1 month after autologous bone marrow transplantation which was much more rapid than that of BFU-E and CFU-GM. After allografting, however, TL-CFU regenerated at a slower rate and reached normal levels between 2 and 6 months after transplantation. We suggest that the delayed restoration of myeloid and erythroid progenitor cells after autologous transplantation is related to a proliferative defect of the graft as a result of the preceding cytotoxic chemotherapy, the underlying malignant disease and/or cryopreservation. The slower recovery of the T lymphocyte precursors after allografting might be due to the immunological interactions between graft and host, the immuno-suppressive therapy and/or the in vitro T cell depletion of the graft.

Blood Cell Count↗
PubMed1987

Characterization of the blast cells in acute leukemia with translocation (4;11): report of eight additional cases and of one case with a variant translocation.

Eight new cases (five adults and three children) of acute leukemia characterized by the presence in bone marrow cells of a t(4;11)(q21;q23)and one similar case, a child, with a t(1;11)(p32;q23) are reported. All patients were diagnosed as having acute lymphoblastic leukemia (ALL) with high-risk features. Immunologically the blast cells of the nine cases showed a strikingly consistent immature lymphoid phenotype, i.e., TdT+, HLA-DR+, B4(CD19)+, CALLA(CD10)-, Smlg-, cmu-, BA-2(CD9)+ corresponding to a "null ALL." In addition, six of nine cases expressed the myeloid marker VIM-D5(CD15). By double immunofluorescence staining it was determined that the VIM-D5(CD15) antigen was expressed by terminal deoxynucleotidyl transferase-positive blast cells, excluding the possibility of double leukemia. In five cases investigation of the Ig heavy chain genes by Southern blot analysis showed clonal rearrangement of both Ig heavy chain gene alleles. These data suggest that the blast cells involved in t(4;11) leukemia represent early B-cell progenitors with "aberrant" expression of myelomonocytic features, possibly related to the 11q23 breakpoint.

Adolescent↗
PubMed1986

Simultaneous occurrence of acute monoblastic leukemia and an abnormal B-cell clone with both cell types characterized by specific cytogenetic and immunological markers.

2 different, unrelated, abnormal clones of cells were found in a patient with acute leukemia, each clone being characterized by specific cytogenetic abnormalities and a distinct immunological phenotype. Bone marrow morphology and cytochemistry indicated an acute monoblastic leukemia, a diagnosis supported by the finding of a t(9;11) in bone marrow cells. In PHA-stimulated blood culture, another abnormal karyotype was found in 16% of the metaphases: 47,XY, + 12, inv(13), t(14;18). Immunologically, the blood contained 3 types of mononucleated cells (MNC): 1) large cells (about 70% of the MNC) with a phenotype consistent with monoblastic/monocytic leukemic cells (My7+, My8+, My906+, My4+, Leu-M3+); 2) small lymphocytic cells with either T-cell characteristics (6% of the MNC); or 3) B-cell monoclonal features (24% of the MNC). The monoclonal B-cell population was Sm kappa +, mu +, delta +, BA-1+, B1+, Y29/55+ and FMC7+. The possible origin of this abnormal (malignant) B-cell population is discussed. However, this B-cell clone was clinically silent and the patient' death precluded further observations.

Acute Disease↗
PubMed1986

Characterization of normal and regenerating bone marrow cells with a panel of monoclonal antibodies.

To obtain baseline data for the diagnosis of residual leukaemia or lymphoma in bone marrow (BM), BM samples of 12 normal adults, 6 patients treated with chemotherapy for solid tumours and 6 patients treated with chemotherapy for leukaemia or lymphoma during remission were assessed with a panel of monoclonal antibodies by fluorescence microscopy immediately following chemotherapy. A large variability between normal individuals was found concerning the percentages of T lymphocytes and T cell subsets, B lymphocytes, HLA-DR+ and OKT10+ cells, due to variation in BM composition and, presumably, peripheral blood contamination. The regenerating BM cells also showed a large variability and, in addition, sometimes very high percentages (up to 19%) of CALLA+, c mu + s mu-, c mu + kappa lambda- and TdT+ cells were found. The interpretation of data on individual BM samples of patients assessed for leukaemia or lymphoma should therefore be related to: the amount of contaminating peripheral blood cells; the cellular composition of the BM samples as determined by May-Grünwald Giemsa staining; baseline data of age-matched normal controls and of regenerating BM of patients without haematological diseases.

Adolescent↗
PubMed1986

Graft-versus-host disease following transplantation of 'one log' versus 'two log' T-lymphocyte-depleted bone marrow from HLA-identical donors.

Prevention of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation, requires the depletion of mature T-lymphocytes from bone marrow grafts. The optimal degree of T-cell reduction is still an open question. We compared two procedures of T-cell separation in 18 consecutive recipients of genotypically HLA-matched bone marrow, who also received cyclosporin A for 6 months. The first method (A) was based on a discontinuous albumin gradient fractionation and resulted in an average T-lymphocyte content of 50 X 10(5)/kg body weight (n = 9 patients); the second method (B) was based on E-rosette sedimentation and reduced the contamination to 15 X 10(4) grafted T-lymphocytes/kg body weight on the average (n = 9 patients). Thus, approximately 90 and 99% of the original T-lymphocytes were removed from the marrow grafts respectively. Of the seven patients of the first group who were at risk of GVHD (excluding two cases of early death), five developed a minimal-to-moderately severe acute GVHD and in two cases chronic GVHD ensued. Lethal GVHD was not seen. Of group B, all recipients engrafted and none developed GVHD (0/9). The difference in the frequency of GVHD between the two groups was highly significant (P less than 0.0025). These data confirm our preclinical studies. They demonstrate that a one-log T-lymphocyte reduction of the marrow inoculum, when combined with cyclosporin A prophylaxis after major histocompatibility complex (MHC)-matched transplantation, is still associated with a considerable incidence of GVHD, whereas a two-log reduction of T-lymphocytes may provide full protection against acute GVHD.

Adolescent↗
PubMed1985

High-dose methotrexate with leucovorin rescue: effectiveness in relapsed hairy cell leukemia.

Six patients with relapsed hairy cell leukemia after splenectomy were treated with high-dose methotrexate and leucovorin rescue. Five patients had objective responses as determined by improved blood counts. In two of them, the response has continued for more than 14 and 44 months, respectively. Intensive treatment with high-dose methotrexate and leucovorin rescue was well tolerated and no significant myelosuppression was seen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Transplantation of non-purified autologous bone marrow in patients with AML in first remission.

Four patients with acute myeloid leukemia (AML) were treated with high-dose cyclophosphamide and total body irradiation followed by reinfusion of a portion of their own bone marrow collected during remission. This procedure was applied when the patients were in complete remission. They did not receive further maintenance chemotherapy after grafting. The use of bone marrow for grafting that had been pre-exposed to high-dose chemotherapy for remission induction did not preclude good hematologic regeneration. All patients showed stable remissions that lasted for 64+, 21, 40+, and 19+ months, respectively. Death in the second patient was due to a medullary relapse of the leukemia. Autologous bone marrow transplantation in patients with AML in remission may permit lasting remissions, even when applied without additional chemotherapy and attempts to purify the marrow of neoplastic cells.

Adolescent↗