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Biomedical subjects

C Haanen

Publications and source records attributed to C Haanen.

At least 73 records · Page 4Linked to original sources
PubMed1990

Intensive antileukemic treatment of patients younger than 65 years with myelodysplastic syndromes and secondary acute myelogenous leukemia.

Intensive antileukemic treatment was evaluated in 22 patients with secondary acute myelogenous leukemia (sAML) and 14 patients with myelodysplastic syndrome (MDS). Results of combination remission-induction chemotherapy were compared with 126 patients contemporarily treated for primary AML. The duration of hypoplasia, induced by remission induction chemotherapy, tended to be longer in the sAML and MDS patients when compared to de novo AML, but reached significance only for the duration of thrombocytopenia: 26 days versus 18 days (P less than 0.01). The number of hypoplastic deaths during remission-induction chemotherapy of patients with sAML and MDS was low. Four of the 36 patients treated for sAML or MDS died during hypoplastic phases induced by remission-induction chemotherapy. The complete remission (CR) rates were similar in primary AML (67%), sAML (62%), and MDS (64%). The CR rates of patients younger than 45 years were 75% for de novo AML, 75% for sAML, and 71% for MDS. Remission rates in patients older than 45 years were identical in the three subgroups but significantly (P less than 0.005) inferior to those obtained in younger patients: 56%, 50%, and 57%, in de novo AML, sAML, and MDS, respectively. The remission duration without bone marrow transplant (BMT) was significantly shorter (P less than 0.01) in MDS and sAML when compared with primary AML. Long-lasting CR in MDS and sAML was only obtained in three of the six patients treated with allogeneic BMT. Intensive antileukemic therapy could be considered in young patients with MDS and life-threatening cytopenias or patients with sAML.

Adult↗
PubMed1990

Simultaneous measurement of DNA content and cell-surface immunofluorescence of human bone marrow cells using a single laser flow cytometer.

This paper describes the measurement of S phase DNA content in human bone marrow subpopulations using a single laser method for bivariate analysis of DNA content and cell-surface immunofluorescence (s-IF). Low density (less than 1.077 g/ml) bone marrow cells were labeled with a panel of unconjugated monoclonal antibodies (MoAb) for the lymphoid (CD2 + CD19), T-lymphoid (CD2), B-lymphoid (CD19), erythroid (anti-glycophorin-A), myelomonocytic (CD13, CD33; single and as cocktail) and monocytic (CD14) lineages. A fluorescein isothiocyanate (FITC)-conjugated goat anti-mouse label was used as second step. Unfixed, MoAb-labeled cells were incubated for 24 h with a hypotonic propidium iodide solution for DNA staining. Cells were analysed on a single-laser flow cytometer, operating at 488 nm. The effect of the combined staining protocol upon both s-IF and DNA stainability was evaluated. Only a slight decrease (mean: 29.0%) in s-IF intensity was observed after DNA staining. The percentages of immunofluorescent cells in the bone marrow samples of 10 normal individuals before and after DNA staining were essentially unchanged for all the MoAbs used. The DNA histograms of the immunophenotypically defined subpopulations were of excellent quality with a mean coefficient or variation of 1.8%. This procedure allows the assessment of very low levels of S-phase DNA content, as measured in normal low density blood cells of 8 healthy volunteers (mean 0.07%).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1990

A randomized comparison of intensive maintenance treatment for adult acute myelogenous leukemia using either cyclic alternating drugs or repeated courses of the induction-type chemotherapy: AML-6 trial of the EORTC Leukemia Cooperative Group.

Out of 515 evaluable patients (median age, 47 years) who entered the study from 1983 to 1986, 67.4% achieved complete remission (CR) after one cycle (256) or two cycles (91) of daunorubicin (DNR) (45 mg/m2 days 1-3), cytosine arabinoside (Ara-C) (200 mg/m2 i.v. days 1-7), and vincristine (VCR) (1 mg/m2 day 2). A partial remission was achieved by 3.7% of patients, 15% were resistant, 11.3% died during hypoplasia, and 2.7% died during induction. Patients achieving CR received one consolidation course in which administration of DNR was limited to 1 day. Two hundred and forty-eight patients were randomized for six courses of maintenance every 6 weeks: either DNR + VRC day 1 + Ara-C s.c. days 1-5, or AMSA 150 mg/m2 day 1 alternating with high-dose (HD)-Ara-C 3 g/m2 q12 h day 1 + 2 or 5-azacytidine 150 mg/m2 days 1-3. Two hundred and thirty-three patients were randomized when bone marrow transplantation (BMT) had not been planned or performed and 15 patients were randomized before the BMT. Sixty patients received BMT, 17 autografts, and 43 allografts. Median time from CR to BMT was 15 weeks. Forty-two patients were not randomized mainly because of toxicity or treatment refusal. Median DFS for both chemotherapy groups was 12 months and 23% were alive at 4 years. Median survival from CR was 22 months, and 34% were alive at 4 years. There was no difference in disease-free interval (DFI) and disease-free survival (DFS) between the two chemotherapy arms. Of 60 transplanted patients, 42% were alive at 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Recombinant interferon-alpha, but not interferon-gamma is effective therapy for essential thrombocythemia.

Recombinant interferon-gamma with a starting dose of 0.5 mg 3x/week subcutaneously, was administered to 6 patients with essential thrombocythemia (median platelet count 1172 X 10(9)/l, range 602-1564). Four of the patients had received alkylating agents previously. Hematological remission, defined as a decrease in platelet counts to less than or equal to 350 X 10(9)/l, was observed in none of these patients. Subsequently 4 of these 6 patients, supplemented by 2 others were treated with interferon-alpha 2c at a dose of 5 X 10(6) U daily subcutaneously. Five patients showed hematological remission. In case of hematological remission the interferon-alpha doses was reduced to 5 X an thereafter to 3 X weekly 5 X 10(6) U. During an observation period ranging from 12-41 weeks platelet counts remained normal in all patients. Side-effects were mild and consisted of fever, myalgias, malaise and itching occurring mainly during the first month of treatment. No dose adaptation was required. The patients treated previously with interferon-gamma experienced the side effects from this drug less tolerably than those from the alpha-compound. These observations suggest that recombinant interferon-alpha may be an effective drug in treating essential thrombocythemia resulting in a sustained response.

Adult↗
PubMed1990

DNA strand breaks in human leukocytes induced by chemotherapy and total body irradiation.

The occurrence of DNA strand breaks and/or DNA alkali-labile sites in peripheral blood leucocytes was demonstrated ex vivo in three patients during and after bone marrow ablative chemotherapy and total body irradiation (TBI) with use of fluorometric analysis of the DNA unwinding rate in alkaline solution (FADU assay). DNA damage was apparent after cyclophosphamide administration and after TBI, related to the amount of the applied dose. In vivo repair occurred within 24 hours, although not to pretreatment values. Demethoxydaunorubicin and busulfan at the dosages used did not induce measurable DNA strand breaks. The experiences described may be developed further to study ex vivo the occurrence of DNA lesions in patients during and after anticancer treatment. Such studies may be of value in comparing the DNA damaging potential of different chemotherapeutic or radiotherapeutic regimens and as a biological assessment of DNA damage after nuclear casualties in cases where the dose is greater than 1-2 Gy and measurement can be made within due time after the ionizing exposure.

Adult↗
PubMed1990

Phenotypic and functional changes of tumour cells from patients treated with monoclonal anti-idiotypic antibodies.

In this paper data are presented indicating that immunotherapy with monoclonal anti-idiotypic antibodies (MoAb anti-id) can provoke different responses in the B-cell tumour concerned. With respect to the course of disease during and after immunotherapy, the in vitro findings may very well explain the in vivo observations in the two patients (D.E.F., B.O.R.) with B-cell chronic lymphocytic leukaemia (B-CLL) who were treated with MoAb anti-id. After initial tumour reduction, there was a recurrence of tumour cells with altered functional and phenotypic properties. In both cases the recurring tumour cells still expressed the same idiotype. In one patient (D.E.F.) the phenotypic changes (a surface Ig change from IgM, IgG, IgA, and IgD to weakly positive IgM and IgD) and functional changes (a 10-fold increase in [3H]thymidine uptake and a decreased idiotype secretion in vitro), together with the in vivo findings with respect to the course of disease--at relapse an impressive tumour regrowth rate with constant serum idiotype level--suggest that immunoselection might have taken place favouring the survival and relapse of a less mature, more aggressive tumour cell population with a lower idiotype expression. In the second patient (B.O.R.), the phenotypic changes (an isotype change from IgM and IgD to IgM with the loss of IgD, and a gradual decrease in expression of CD19 and CD24) and functional changes (a 10-fold increase of idiotype secretion in vitro), together with the in vivo finding that the serum idiotype level had increased 25-fold compared with the preimmunotherapy serum level with comparable tumour load, strongly suggest an immunotherapy-induced differentiation of the malignant B cell. We also describe an increased expression of CD74, detected by MoAb BoM22, on the recurring tumour cells of patient B.O.R., whereas the expression of HLA-DP, -DQ and -DR did not change. The significance of this finding is unclear.

Antibodies, Anti-Idiotypic↗
PubMed1990

Continuous intravenous administration of daunorubicin and cytarabine for remission induction of poor risk acute myelogenous leukaemias and myelodysplastic syndromes.

Seventeen consecutively admitted poor risk acute myeloid leukaemia (AML) patients and 4 patients with myelodysplastic syndrome (MDS) were treated with a remission-induction regimen consisting of a 7-day continuous intravenous infusion of conventional doses of cytarabine and of three 24-h constant rate infusions of daunorubicin administered intermittently on days 1, 3 and 5. The diagnoses were: relapsed primary AML in 6 patients, secondary AML in 11 patients (9 untreated, 2 relapsed) and MDS in 4 patients. The median age was 50 yr. Five of 6 patients with relapsed primary AML, 3 of 11 patients with secondary AML and 2 of 4 patients with MDS achieved complete remission (CR). The overall CR rate was 48% with a median remission duration of 5 months (range: 0.25-20 months). Few acute toxic side effects were observed thanks to the constant rate of infusion of daunorubicin.

Acute Disease↗
PubMed1989

Autologous transplantation of bone marrow purged in vitro with anti-CD7-(WT1-) ricin A immunotoxin in T-cell lymphoblastic leukemia and lymphoma.

Seven patients with high-risk acute T-cell lymphoblastic leukemia (T-ALL) and six with T cell lymphoma (T-LL) were treated with autologous bone marrow transplantation (ABMT) after in vitro purging of their bone marrow with WT1 (CD7)-ricin A-chain immunotoxin. CD7 expression on the tumor cells showed large variations between the individual patients and was highly related to the specific cytotoxicity of WT1-ricin A. Incubation of bone marrow with up to 10(-8)mol/L WT1-ricin A in the presence of 6 mmol/L NH4Cl did not compromise the growth potential of the hematopoietic progenitors CFU-GM, CFU-GEMM, and BFU-E. Hematologic engraftment (greater than 10(9) leukocytes/L) occurred within a normal time period (median, 17 days). Seven patients are alive and in complete remission (CR) at 48+, 44+, 40+, 26+, 11+, 7+, and 6+ months after ABMT. Four patients relapsed within 6 months after ABMT. Two of them had the lowest CD7 expression on their tumor cells, the other two were transplanted in CR2 and CR3. Two patients died from transplantation related infections. The immunologic reconstitution was delayed, although the numbers of T cells reached normal levels within 1 month. The number of CD7+ cells remained low up to 1 year after transplantation. The T4/T8-ratio was decreased for at least 6 months. The T-cell response to mitogens recovered to normal levels after 1 year. This study shows that ABMT with WT1-ricin A purged bone marrow in high-risk T-cell malignancies results in a complete hematopoietic and a delayed immunologic reconstitution. The actuarial relapse free survival is 61% at 3 years.

Adolescent↗
PubMed1989

Cytotoxic potential of anti-CD7 immunotoxin (WT1-ricin A) to purge ex vivo malignant T cells in bone marrow.

With the perspective of bone marrow purging in autologous transplantation, we investigated the cytotoxicity of the anti-T cell immunotoxin (IT) WT1-ricin A (anti-CD7) to malignant T cells obtained from patients with T cell acute lymphoblastic leukaemia or lymphoma. The cytotoxic efficacy of IT was based on the extent of protein synthesis inhibition. Cytotoxicity of IT to malignant T cells showed a dependency on antigen density comparable to the T cell lines GH1, CEM, Jurkat, HSB-2 and HPB-ALL and was enhanced considerably in the presence of 6 mM ammonium chloride. The ultimate proof of cell kill can only be obtained from clonogenic assays; however, culturing of malignant T cells was not feasible. Therefore these assays were performed with the cell line CEM that expresses comparable amounts of CD7 antigen as malignant T cells of most patients. More than 6-logs of CEM appeared to be eliminated after incubation with 10(-8) M WT1-ricin A. Immunotoxins are only effective after entering the target cell. The pattern of internalization of the IT was determined by means of 125I-WT1. After internalization the CD7 antigen was re-expressed on the cell membrane. This enables a long incubation period resulting in an increased elimination of malignant T cells. Even after 16 h the IT was still accumulated intracellularly. This pattern of continuous uptake of IT was reflected in a gradually increasing cytotoxicity with incubation time. Effective bone marrow purging can be carried out without adverse effects on progenitor cells with 10(-8) M WT1-ricin A. At that concentration the antibody binding capacity was saturated. We showed that the protein synthesis inhibition in malignant T cells by WT1-ricin A is comparable to the inhibition in T cell lines and that high amounts of CEM cells can be killed. These data suggest that cell lines can be used to test the efficacy of IT to malignant T cells. WT1-ricin A appears to be very potent for the purging of autologous bone marrow from patients with T cell malignancies.

Ammonium Chloride↗
PubMed1989

Dose intensity of MOPP chemotherapy and survival in Hodgkin's disease.

The association between dose intensity of chemotherapy with the rate of complete remission (CR), the duration of disease-free survival (DFS), and overall survival (OS) was separately analyzed for 67 patients initially treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), and for 75 patients in relapse following radiotherapy who had received MOPP as a salvage regimen. In both groups of patients, the fraction of the total dose of mechlorethamine delivered in all cycles divided by the planned dose for six cycles was strongly associated with OS (P = .002 for patients receiving initial MOPP and P = .02 for the salvage group, respectively). B symptoms were independent of drug-derived variables associated with OS (corresponding P values .03 for initial MOPP and .004 for the salvage group). The predictive value of mechlorethamine dosage with regard to OS was retained in an analysis restricted to the patients receiving greater than or equal to six cycles of chemotherapy. In the initial chemotherapy group, mechlorethamine dosage was associated with attainment of CR but none of the variables tested was predictive of DFS. In the salvage chemotherapy group, mechlorethamine dosage was associated with attainment of CR and duration of DFS as well. The results emphasize that, besides tumor characteristics, optimal dosage of chemotherapy is of great importance for survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Mixed hematopoietic chimerism after allogeneic transplantation with lymphocyte-depleted bone marrow is not associated with a higher incidence of relapse.

Using red cell phenotyping, cytogenetic analysis of blood lymphocytes, chromosome studies of bone marrow cells, and restriction fragment length polymorphism (RFLP) studies of peripheral blood cells, we demonstrated a high number of mixed chimeras after allogeneic bone marrow transplantation (BMT). Donor marrow from HLA-A, -B, and -DR identical, mixed lymphocyte culture (MLC) nonreactive siblings was depleted of 98% of lymphocytes using counterflow centrifugation. Thirty-two of 48 recipients (67%) appeared to be mixed chimeras at 6 months after transplantation. The high number of mixed chimeras is probably a result of lymphocyte depletion of the marrow graft and the high sensitivity of red cell phenotyping for the demonstration of minor cell populations (at levels as low as 0.01%). The probability of relapse-free survival from 6 months to 4 years after BMT was 85% for the mixed chimeras and 65% for the complete donor chimeras. We conclude that in this study, mixed chimerism is not associated with a higher incidence of relapse.

Adolescent↗
PubMed1989

Alternating v repeated postremission treatment in adult acute myelogenous leukemia: a randomized phase III study (AML6) of the EORTC Leukemia Cooperative Group.

The value of a postremission treatment in acute myelogenous leukemia (AML), with alternating combinations of non-cross-resistant drugs, has been prospectively assessed. Of 515 evaluable patients, 347 (67.4%) entered into complete remission (CR), following induction treatment with daunorubicin (DNR), vincristine (VCR), and cytosine arabinoside (ara-C). After one consolidation course, 248 patients were randomized for six courses of intensive maintenance: either repeated treatment with DNR-VCR-ara-C, or alternating treatment where amsacrine (AMSA) was combined with high dose ara-C on cycle 1,3, and 5 and with 5-azacytidine on cycle 2, 4, and 6. Ninety-nine patients were not randomized: 57 were introduced in a bone marrow transplantation (BMT) program, and 42 went off study, mainly for treatment toxicity or refusal. The main prognostic factors for achievement of CR were performance status, cytogenetics, and age, and for the disease-free survival (DFS): age and number of courses to CR. The rate of second remission was fairly high (64%) for patients relapsing off therapy. The DFS appeared identical (median, 53 weeks), in the two randomized arms, the alternating treatment not showing superiority to the repeated one, in spite of an increased toxicity. The median overall survival for patients achieving a CR was 90 weeks. The reason for the failure of alternating maintenance treatment to improve the DFS is probably related to an insufficient dose intensity: five patients who relapsed during maintenance arm B achieved a second CR with a more intensive combination of high-dose ara-C and AMSA. In addition, 60 patients underwent a BMT (43 allogeneic and 17 autologous). The DFS of patients treated with allogeneic BMT tended to be superior to the one obtained with the chemotherapy program. However the overall survival, as well as the event-free survival, seemed equivalent, including patients who relapsed before the planned BMT. Comparisons between allogeneic BMT, autologous BMT, and intensive consolidation during first CR deserve further prospective studies in AML.

Adolescent↗
PubMed1989

Anthracyclines added to the conditioning regimen for allogeneic bone marrow transplantation are associated with a slower haematopoietic recovery.

Factors which may influence haematopoietic recovery after allogeneic bone marrow transplantation were analysed. Forty-six evaluable patients transplanted with lymphocyte-depleted marrow for acute lymphoblastic leukaemia, acute non-lymphoblastic leukaemia, chronic myeloid leukaemia, myelodysplastic syndrome and severe aplastic anaemia were studied. The median time for platelet recovery to greater than or equal to 20 and to greater than or equal to 50 x 10(9)/l was 21 (9-72) and 26 (11-86) days respectively. The neutrophil recovery to greater than or equal to 0.5 x 10(9)/l and the leucocyte recovery to greater than or equal to 1.0 x 10(9)/l was 19 (8-47) and 18 (6-47) days respectively. No relation was found between the number of infused granulocyte-macrophage colony-forming cells, erythroid burst-forming cells, diagnosis, graft-versus-host disease, antibiotic administration and recovery. Addition of a continuous 6-day infusion of anthracyclines to the conditioning regimen delayed the median recovery of platelets, neutrophils and leucocytes by 7-9 days. Fever during aplasia also inhibited haematopoietic recovery. It is speculated that leakage of intracellular anthracyclines after bone marrow infusion or fever secondary to anthracyclines-induced oromucositis is responsible for the delayed bone marrow recovery.

Adolescent↗
PubMed1989

Intensive chemotherapy for patients with myelodysplastic syndromes and acute myelogenous leukaemia younger than 65 years.

Intensive antileukemia treatment was evaluated in 22 patients with untreated secondary acute myelogenous leukemia (sAML) and 14 patients with bad prognosis myelodysplastic syndrome (MDS). Results of combination remission-induction chemotherapy were compared with 126 patients treated for primary AML. The duration of hypoplasia tended to be longer in the sAML and MDS patients when compared to de novo AML, but reached significance only for the duration of thrombocytopenia: 26 days versus 18 days (p less than 0.01). The complete remission (CR) rates were similar in primary AML: 67%, sAML: 62%, and MDS: 64%. The CR rates of patients younger than 45 years were 75% for de novo AML, 75% for sAML, and 71% for MDS. The number of hypoplastic deaths during remission-induction chemotherapy of patients with sAML and MDS was low. Four of the 36 patients treated for sAML or MDS died during subsequent hypoplastic phases induced by remission-induction chemotherapy. The remission duration without bone marrow transplantation (BMT) was significantly shorter (p less than 0.03) in MDS and sAML, when compared with primary AML. Longlasting complete remissions in MDS and sAML were only obtained in 3 of the 6 patients treated with allogeneic BMT. Intensive antileukemic therapy should be considered in young patients with MDS and life-threatening cytopenias or patients with sAML or RAEBt.

Adult↗
PubMed1989

Diabetes insipidus associated with leukaemia.

Three cases of leukaemia complicated by pituitary diabetes insipidus are presented. In one patient diabetes insipidus developed five months before acute myelomonocytic leukaemia became apparent. The two other patients suffered from acute myelomonocytic leukaemia and from a blastic transformation of chronic myeloid leukaemia. In one case a transient cure of diabetes insipidus was obtained after intrathecal chemotherapy and irradiation of the skull.

Adult↗