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H G Sayer

Publications and source records attributed to H G Sayer.

34 records · Page 2Linked to original sources
PubMed2001

Dose-reduced conditioning for allografting in 44 patients with chronic myeloid leukaemia: a retrospective analysis.

This retrospective study describes the outcome of patients with chronic myeloid leukaemia after allografting using dose-reduced conditioning with fludarabine and busulphan. Forty-four Philadelphia chromosome (Ph)-positive patients were transplanted in nine German centres; 26 patients were in chronic phase, 11 in accelerated phase and seven in blast crisis. Thirty-four patients achieved complete remission, with 18 alive and disease-free at a median follow-up of 562 d (range 244-922 d). Grade II-IV acute graft-versus-host disease (GVHD) incidence was 43%. Twenty patients died, 15 of causes unrelated to relapse. Risk factors predisposing to graft failure by univariate analysis were an unrelated donor (8/23 compared with a related donor 2/21, P = 0.07) and interferon therapy within 90 d of transplant (4/6 versus 3/17, P = 0.025). At the last follow-up, of 31 patients for whom molecular or cytogenetic data were available, 16 (52%) were polymerase chain reaction-negative, and seven (23%) were Ph-negative by fluorescent in situ hybridization. These findings demonstrate that dose-reduced conditioning with fludarabine and busulphan provides durable engraftment and a low rate of relapse. However, in this population, many of whom were not eligible for high-dose conditioning due to age, reduced performance status, previous complications or extensive pre-treatment, these data highlight the need for effective anti-infectious and GVHD prophylaxis. In addition, this study supports the discontinuation of interferon therapy at least 90 d before transplant

Adult↗
PubMed1998

Correlation between granulocyte/macrophage-colony-forming units and CD34+ cells in apheresis products from patients treated with different chemotherapy regimens and granulocyte-colony-stimulating factor to mobilize peripheral blood progenitor cells.

We examined the efficiency of disease-specific "standard" chemotherapies epirubicin, cyclophosphamide (EC); cyclophosphamide, vincristine, doxorubicin, etoposide, prednisolone (CHOEP); epirubicin, ifosfamide (EPI/IFOS) for peripheral blood progenitor cell (PBPC) mobilization in comparison to well-characterized mobilization protocols, i.e. etoposide, ifosfamide, cisplatin, epirubicin (VIPE) and dexamethasone, carmustine, etoposide, cytarabine, melphalan (DexaBEAM). Twenty-seven patients with various malignancies underwent 75 apheresis procedures for PBPC collection. Median cell yields from all 75 aphereses were 1.18 x 10(5) mononuclear cells/kg [range (0.28-3.7) x 10)8)], 1.4 x 10(5) granulocyte/macrophage-colony-forming units (CFU-GM)/kg [range (0.2-11) x 10(5)] and 3.3 x 10(6) CD34+cells/kg [range (0.35-17.7) x 10(6). CD34+/ CD90+ cells could be mobilized by all mobilization regimens used. The difference observed in the mobilization of CD34+ cells was only of low significance when the mobilization regimens were compared, whereas the mobilizations of MNC and CFU-GM were significantly different between the groups. Breast cancer patients treated with the VIPE regimen (including pretreated women) had a significantly higher CFU-GM rate than patients treated with EC (P=0.0005). Mobilized CD34+ PBPC were correlated with CFU-GM in all apheresis products. The linear correlation coefficients differed for the various mobilization groups: DexaBEAM (r=0.9, P < 0.0001), VIPE (r=0.68, P=0.0024), CHOEP (r=0.52, P=0.022), EPI/ IFOS (r=0.34, P=0.11) and EC (r=0.23, P=0.2). We conclude that clonogenic assays can provide additional information about the autotransplant quality, particularly when alternative or new mobilization regimens are being investigated.

Antigens, CD34↗
PubMed1997

[High dose chemotherapy of solid tumors].

BACKGROUND: The availability of hemopoetic growth factors and the retransfusion of autologous peripheral blood stem cells (PBSC) have enabled high-dose chemotherapy (HDT) options for the treatment of advanced solid tumours, during recent years. Though the transfusion of PBSC can manage the myelosuppression, dose-escalation ist still limited by non-haematological toxicity. METHOD: Usually, HDT has been given after a proceeding dose-intense chemotherapy that allowed the evaluation of chemosensitivity of the disease and resulted in a stem cell mobilization into the peripheral blood. The autologous bone marrow transplantation has almost completely been replaced by retransfusion of PBSC together with hemopoietic growth factors as specific supportive treatment. The PBSC are harvested by apheresis using a blood cell separator. RESULTS: Results on the efficacy of HDT are available for breast, testicular, ovarian, small cell lung cancer as well as melanoma, glioblastoma and soft-tissue sarcoma. The studies showed the feasibility and efficacy of HDT with tolerable toxicity. CONCLUSION: High-dose chemotherapy will be of increasing importance in the treatment strategies of primary solid tumors, in the near future.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Increased risk of infection in marrow transplant patients receiving methylprednisolone for graft-versus-host disease prevention.

One hundred forty-seven patients with hematologic diseases and treated by allogeneic marrow transplants received graft-versus-host disease (GVHD) prevention with methotrexate and cyclosporine. In addition, 73 of the 147 patients were randomized to receive methylprednisolone during the first 35 days after transplant to improve GVHD prevention, whereas 74 patients were randomized not to receive methylprednisolone. The randomized trial enabled us to examine whether methylprednisolone increased the risk of infection after marrow grafting. Charts of study patients were analyzed retrospectively for infection events including bacteremia, septicemia, and fungemia. The randomization was stratified by diagnosis, patient age, genotypic HLA identity, and assignment to laminar airflow room isolation. All patients were given a short course of methotrexate (no longer than 11 days) and cyclosporine for no longer than 180 days after marrow transplantation. Methylprednisolone was begun on the day of marrow grafting at a dose of 1 mg/kg body weight intravenously in divided AM and PM doses through day 22. Methylprednisolone was administered at a dose of 0.5 mg/kg in divided doses from days 22 through 35, and then discontinued. Infections were analyzed for the time interval ending on day 65 after transplantation, which included the period of methylprednisolone administration and 1 month thereafter. Seventy-one episodes of first infection events were observed in patients receiving methylprednisolone compared with 47 episodes in patients not receiving the drug. Predominant infections were bacteremias, followed in descending order by fungemias and septicemias. The most prevalent organisms cultured were gram-positive bacteria, especially coagulase-negative Staphylococcus and Streptococcus species. Pseudomonas species were the most common gram negative bacteria, and the most prevalent fungus was Candida albicans. Multivariable Cox regression analysis showed that patients receiving methylprednisolone had a 1.5 times higher risk of infection (P = .03), with acute GVHD being another independent risk factor for infections (P = .005). Methylprednisolone, when added to GVHD prevention by methotrexate and cyclosporine, increases the risk of infection during the early posttransplantation period.

Anemia, Aplastic↗
PubMed1993

Constant intravenous pentoxifylline infusions in allogeneic marrow transplant recipients: results of a dose escalation study.

An uncontrolled open prospective dose escalation study of daily constant-rate 24-h i.v. pentoxifylline (PTX) infusions was performed in 24 consecutive adult patients with hematologic malignancies undergoing allogeneic BMT. The objective of this study was to determine the maximum tolerable dose and to evaluate steady-state plasma concentrations of PTX and its major active 5-hydroxylated metabolite (MI) with this application route. On each of three dose levels of PTX (10, 15 and 20 mg/kg/day), eight patients were enrolled in this study. The prominent dose-dependent and dose-limiting adverse effect attributable to PTX infusions was moderate to severe nausea and vomiting which occurred on the 15 mg/kg and 20 mg/kg dose levels. In addition, one patient on each of the higher doses developed central nervous system toxicity which manifested as acute obtundation and myoclonias. Monitoring of steady-state plasma concentrations revealed that metabolite MI contributed 70-80% to both active compounds with a dose-dependent increase of parent drug and metabolite MI concentrations. In patients pretreated by high-dose busulfan and cyclophosphamide (CY), steady-state plasma concentrations of metabolite MI were significantly increased on all dose levels over those of patients who received total body irradiation and CY as a preparative regimen. Furthermore, impairment of excretory liver function led to significant accumulation of parent drug and metabolite MI. In conclusion, constant i.v. PTX infusions in allogeneic marrow transplant recipients are limited by dose-dependent nausea and vomiting with an estimated maximum tolerable dose in the range of 10 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Evidence that sustained growth suppression of intestinal anaerobic bacteria reduces the risk of acute graft-versus-host disease after sibling marrow transplantation.

The influence of intestinal bacterial decontamination on the occurrence of grades II to IV acute graft-versus-host disease (GVHD) was retrospectively analyzed in 194 predominantly adult patients treated by genotypically identical sibling marrow transplantation under conditions of strict protective isolation and intestinal antimicrobial decontamination. Forty-five patients (23%) developed acute GVHD and univariate analysis identified four features that significantly increased the risk for this reaction: chronic myeloid leukemia as the underlying disease, as compared with all other disease categories (P < .0001); female marrow donors for male recipients, as compared with other gender combinations (P < .005); ineffective, as compared with sustained growth suppression of intestinal anaerobic bacteria (P < .006); and methotrexate as the sole immunoprophylactic compound, as compared with cyclosporine containing regimens (P < .05). Using the duration of anaerobic growth suppression as a time-dependent explanatory variable, proportional hazards regression analysis confirmed these features as independent predictors for acute GVHD with relative risk estimates of 1.9 (95% confidence interval [CI], 1.3 to 2.7) for the immunoprophylactic regimen (P < .0004), of 1.8 (95% CI, 1.3 to 2.5) for the underlying disease (P < .0005), of 1.7 (95% CI, 1.2 to 2.5) for anaerobic decontamination (P < .002), and of 1.3 (95% CI, 1.1 to 1.6) for the donor/recipient gender combination (P < .008), respectively. Best subset selection modeling also identified the quality of anaerobic decontamination as the third most important predictor for acute GVHD, when all four significant features were included. Estimates of acute GVHD stratified by the quality of anaerobic bacterial growth suppression showed a strong influence of anaerobic decontamination in patients burdened by at least one of the other unfavorable factors (P < .009). In conclusion, this study provides strong evidence that sustained growth suppression of intestinal anaerobic bacteria after clinical sibling marrow transplantation can independently modulate the occurrence of grades II to IV acute GVHD, which is in concordance with previous results from animal transplantation models. Antimicrobial chemotherapy specifically targeted to the intestinal anaerobic bacterial microflora may be complementarily useful in preventing acute GVHD and should be investigated in a prospective trial.

Adolescent↗
PubMed1991

[Maintenance of remission in acute myeloid leukemia by allogeneic or autologous bone marrow transplantation].

Over a 10-year period 120 patients (58 women, 62 men; median age 33 [14-53] years) with acute myeloid leukaemia were treated by allogenic (n = 90) or autologous bone marrow transplantation to maintain remission. After a median observation time of 41 (11-126) months 64 patients (53%) remain alive without recurrence of leukaemia. Ten years after allogenic transplantation performed during the first complete remission the probability of disease-free survival is 50 +/- 8%, as compared with 50 +/- 9% at 4.5 years after autologous transplantation. Significant factors influencing disease-free survival after allogenic transplantation during the first complete remission were the time interval up to the onset of remission and the length of the remission before transplantation. The chance of disease-free survival after allogenic transplantation in the second complete remission does not so far differ from the results achieved by transplantation in the first complete remission. The risk of recurrence after autologous transplantation in the first complete remission (47 +/- 10%) is significantly higher than that following allogenic transplantation (18 +/- 10%, P less than 0.0001). Acute graft versus host reactions occurred in 16% and chronic reactions in 36% of patients after allogenic transplantation. The mortality was 38% after allogenic transplantation and 7% after autologous transplantation.

Acute Disease↗
PubMed1991

Initial treatment of acute graft-versus-host disease with a murine monoclonal antibody directed to the human alpha/beta T cell receptor.

A murine IgG2b monoclonal antibody directed to the constant part of the human alpha/beta T cell receptor (BMA031) was investigated in a pilot study as an initial treatment for acute graft-versus-host disease (aGvHD) after allogeneic bone marrow transplantation. The treatment protocol consisted of 5 mg BMA031 on 5 consecutive days with continuation of the prophylactic baseline immuno suppression using cyclosporin. Seven patients with grades II-III acute graft-versus-host disease were entered on the protocol and six patients completed the full treatment course. Mild to moderate acute adverse reactions to the first BMA031 infusion occurred in three patients. A nearly complete decline of circulating T lymphocytes was observed during BMA031 therapy, but the T cells returned to pretreatment values within 1 week after the last infusion. Serum pharmacokinetics of free antibody best fitted to a two-compartment open model with a mean initial half-life of 6 h and an estimated mean terminal half-life of 40 h. One patient developed antimurine antibodies of the IgM subclass. In five patients a complete and sustained resolution of all disease manifestations was attained, while in one patient a temporary response of skin involvement with aGvHD was noted. These results indicate that BMA031 can be safely administered as initial treatment of aGvHD. The therapeutic responses observed warrant its further clinical evaluation in this setting.

Acute Disease↗
PubMed1990

Clinical results and the Essen concept of TBI.

Total body irradiation (TBI) prior to bone marrow transplantation (BMT) is applied for treatment of 230 patients in the period 1975-1988. The clinical results of 169 patients treated by four different TBI dosage and treatment techniques are analysed. The risk of leukemic relapse is low after fractionated TBI (9%) as well as after single dose TBI (14%). The lowest frequency of interstitial pneumonitis (21%) occurred when the patient translation technique was used for fractionated homogeneous pa/ap TBI with 10 Gy (8 Gy lung dose) in 4 fractions in 4 days. Prophylaxis of GVHD and the modus of protective environment were two other factors which influence the risk of IP.

Adult↗
PubMed1990

Six weeks of continuous intravenous cyclosporine and short-course methotrexate as prophylaxis for acute graft-versus-host disease after allogeneic bone marrow transplantation.

The feasibility and toxicity of six-week continuous intravenous 3 mg/kg/day cyclosporine (CsA) treatment in conjunction with a short course of methotrexate (MTX) was studied in 69 consecutive patients after HLA genotypically identical bone marrow transplantation. In light of the uncertain efficacy of prolonged oral CsA immunoprophylaxis in preventing de novo chronic graft-versus-host disease (GVHD). CsA treatment was terminated three months after BMT. Sixty-one (88%) patients received the full intravenous regimen and no patient exclusions were necessary due to intolerable adverse effects. Weekly median blood CsA concentrations ranged between 820 ng/ml in the first and 648 ng/ml in the sixth week of treatment. No significant correlation existed between blood CsA concentrations and CsA dosages. Major adverse effects of the regimen included hypertension in 36%, acute nephrotoxicity in 36%, acute hepatotoxicity in 41%, and central nervous system toxicity in 4% of the patients. Since hepatotoxicity occurred predominantly in the early posttransplant period (median onset day 9), the relatively high incidence of this untoward effect might have been additionally caused by MTX and/or the preparative regimen. Blood CsA concentrations and CsA dosages did not significantly correlate with serum creatinine or total and conjugated bilirubin levels. In addition, blood CsA and serum creatinine levels did not differ between hypertensive and normotensive patients. Acute GVHD developed in 16% of the patients. Median CsA doses and blood CsA concentrations were identical for each week after BMT for patients contracting acute GVHD as compared with those without acute GVHD. In 55 patients surviving without acute or secondary chronic GVHD, the cumulative probability of de novo chronic GVHD after termination of CsA treatment was 13%. In conclusion, this regimen was tolerable and provided constant blood CsA concentrations for six posttransplant weeks that were not adversely influenced by the development of acute GVHD. Restriction of CsA treatment to the first three months after BMT appeared not to increase the risk of de novo chronic GVHD, which challenges regimens employing oral CsA immunoprophylaxis for 6-12 months after BMT.

Acute Disease↗
PubMed1989

Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia.

The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI).

Adult↗
PubMed1988

Bone marrow transplantation for myeloblastoma.

A 20-yr-old man with bulky mediastinal and retroperitoneal tumour masses identified as myeloblastoma is described. After a partial remission was induced by aggressive chemotherapy, mediastinal irradiation and retroperitoneal tumour resection, the patient received an allogeneic marrow graft from his HLA-identical sister. The conditioning regimen consisted of high-dose busulfan and cyclophosphamide. The patient has a well-controlled secondary chronic graft-versus-host disease. He is in unmaintained complete remission and in good general condition at 20 months post-transplantation.

Adult↗