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Biomedical subjects

J Szer

Publications and source records attributed to J Szer.

At least 109 records · Page 6Linked to original sources
PubMed1993

Busulphan and melphalan prior to autologous bone marrow transplantation.

Twenty-four patients with a variety of malignant diseases (13 lymphoma, 4 myeloma, 1 ALL, 6 solid tumours) were treated with the alkylating agents busulphan and melphalan as a preparative regimen for autologous BMT. Thirteen males and 11 females, aged 27-53 years (median 39.5 years) received oral busulphan 1 mg/kg q6 h on days -6 to -3, followed by i.v. melphalan 140 mg/m2 on day -2 and infusion of cryopreserved haemopoietic cells on day 0. The major toxicity seen was gastrointestinal with nausea, vomiting and diarrhoea in 17 patients and severe mucositis in 22. There was no evidence of cardiotoxicity, nephrotoxicity, haemorrhagic cystitis or clinical signs of hepatic veno-occlusive disease. Twenty-three patients engrafted with the median duration of neutropenia (< 0.05 x 10(9)/l) 10 days (range 5-63 days) and thrombocytopenia (< 50 x 10(9)/l) 43 days (range 5-350 days). Three patients died of transplant-related complications. Of 15 evaluable patients with active disease at BMT, 9 responded and 6 were refractory. Sixteen evaluable patients were in CR after BMT. Seven relapsed, 1 died in remission and 8 remain in CR 12-46 months (median 29 months) later. Of the group of 13 lymphomas, overall and relapse-free actuarial survival at 36 months was 64% and 58%, respectively, while for the entire group of 24 patients these values were 39% and 34%. Busulphan and melphalan is a safe and inexpensive conditioning regimen for autologous BMT with acceptable toxicity and substantial antitumour activity particularly against lymphomas.

Actuarial Analysis↗
PubMed1993

Effect of peripheral blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy.

The haematopoietic growth factor (HGF), granulocyte colony stimulating factor (G-CSF; filgrastim) substantially shortens the period of severe neutropenia that follows high-dose chemotherapy and autologous bone marrow infusion by stimulating granulopoiesis. Filgrastim also increases numbers of circulating progenitor cells. We have studied the ability of filgrastim to mobilise peripheral blood progenitor cells (PBPC) and assessed their efficacy when infused after chemotherapy on recovery of neutrophil and platelet counts. Seventeen patients with non-myeloid malignant disorders received filgrastim (12 micrograms/kg daily for six days) by continuous subcutaneous infusion. Numbers of granulocyte-macrophage progenitors in peripheral blood increased a median of 58-fold over pretreatment values, and numbers of erythroid progenitors increased a median of 24-fold. Three leukapheresis procedures collected a mean total of 33 (SEM 5.7) x 10(4) granulocyte-macrophage progenitors per kg body weight. 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. Platelet recovery was significantly faster in these patients than in controls who received the same treatment apart from the infusion of peripheral blood progenitors; the platelet count reached 50 x 10(9)/L a median of 15 days after infusion of haematopoietic cells in the study patients compared with 39 days in controls (p = 0.0006). The accelerated neutrophil recovery associated with filgrastim treatment after chemotherapy was maintained. Subsequently, 10 patients received filgrastim-mobilised PBPC without marrow after high-dose chemotherapy. The rate of platelet and neutrophil recovery in these patients was at least equal to that observed in the patients receiving PBPC and bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Treatment of chronic myelogenous leukemia with allogeneic bone marrow transplantation after preparation with busulfan and cyclophosphamide (BuCy2): an update.

Allogeneic bone marrow transplantation (BMT) has been shown to result in long-term disease-free survival in patients with leukemia. However, the utility of this treatment approach is limited by treatment-related morbidity and mortality. We present an update of a study in which a BMT preparative regimen consisting of a 4-day course of busulfan and a 2-day course of cyclophosphamide (BuCy2) was used in patients with chronic myelogenous leukemia. Patient survival depended on disease stage, with a 58% survival rate for patients in first chronic phase, 41% for those in accelerated phase, and 25% for those in the blast transformation stage. There was a significant difference in patient survival between those who received transplants within 1 year of diagnosis and those who received transplants more than 1 year after diagnosis (70% v 40%). This difference appeared to be due to the extent of previous exposure to busulfan. The overall mortality rate in this study was 46%. We conclude that the BuCy2 preparative regimen is similar in effectiveness to regimens that include total body irradiation and results in comparable levels of transplant-related mortality. Our results strongly indicate that patients with chronic myelogenous leukemia who receive BMT within the first year after diagnosis have a significantly better clinical outcome than those who receive BMT later in the course of the disease.

Adolescent↗
PubMed1993

Allogeneic bone marrow transplantation for acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma following preparation with busulfan and cyclophosphamide (BuCy2).

The combination of busulfan (Bu) and cyclophosphamide (Cy) has been found to be effective preparative therapy for patients treated with allogeneic bone marrow transplantation (BMT). We developed the BuCy2 regimen, which contains a lower dose of cyclophosphamide than the original BuCy regimen, in the hope of reducing regimen-related toxicities. We have studied the use of BuCy2 as preparation for allogeneic BMT in patients with acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma. In patients with acute myelogenous leukemia, the leukemia-free survival and regimen-related toxicity rates obtained in our study appear similar to those achieved with other preparative regimens, including those containing Cy and total body irradiation (TBI). BuCy2 is also an effective BMT preparative regimen in patients with acute lymphocytic leukemia and multiple myeloma. Treatment with BuCy2 results in a lower incidence of severe stomatitis and probably of interstitial pneumonia than does treatment with Cy/TBI, but hepatic veno-occlusive disease occurs more frequently in BuCy-treated patients. The incidence of veno-occlusive disease appears to be affected by agents used as prophylaxis for graft-versus-host disease. Compared with Cy/TBI regimens, BuCy treatment is likely to result in fewer delayed effects of treatment, such as impairment of fertility and second malignancies. Current clinical efforts are focusing on ways to improve the antileukemic activity of the BuCy preparative regimen and to reduce regimen-related toxicities.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Donor leucocyte infusions after chemotherapy for patients relapsing with acute leukaemia following allogeneic BMT.

Four patients with acute myeloid leukaemia relapsed within 6 months of allogeneic BMT. Three patients were treated with cytosine arabinoside and amsacrine while the fourth received no chemotherapy. All patients received infusions of leucocytes obtained by repeated leukapheresis from the original bone marrow donor. Three patients developed GVHD requiring immunosuppressive therapy. One of these achieved a complete remission which has been sustained for more than 1 year with 100% donor haematopoiesis. The other patients died with persistent leukaemia 45-134 days after the infusions of donor cells. We conclude that the addition of marrow donor leucocytes to salvage chemotherapy may produce durable remissions in patients with acute myeloid leukaemia relapsing after BMT and that this may be due to a graft-versus-leukaemia effect.

Adult↗
PubMed1992

Treatment of chronic myeloid leukemia with allogeneic bone marrow transplantation after preparation with BuCy2.

One hundred fifteen patients with chronic myelocytic leukemia (CML) were administered busulphan 4 mg/kg for 4 days and cyclophosphamide 60 mg/kg on each of 2 days (BuCy2) followed by allogeneic bone marrow transplantation from histocompatible sibling donors. For 62 patients in chronic phase, 26 in accelerated phase, and 27 in blast transformation, the actuarial survival at 3 years was 58%, 41%, and 25%, respectively. Actuarial probability of relapse was 3%, 12%, and 27%, respectively. Only two patients in chronic phase showed a transient cytogenetic relapse and one of these died from subsequent transplant-related complications, whereas the other remains cytogenetically normal 697 days posttransplant. Patients who were transplanted within 1 year of diagnosis in chronic phase had a survival of 70% compared with 40% when transplanted beyond 1 year from diagnosis. This significant difference in survival was due to transplant-related complications and was correlated with previous exposure to high doses of busulphan. This study indicates that BuCy2 is a useful conditioning regimen for marrow transplantation in patients with CML and results in similar survival statistics and transplant-related mortality as would be expected with conditioning regimens containing total body irradiation. It is possible that relapse after BuCy2 may be lower than expected with regimens containing total body irradiation, but larger analyses are required.

Adolescent↗
PubMed1992

Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy.

The haemopoietic growth factor granulocyte colony-stimulating factor (G-CSF; filgrastim) substantially shortens the period of severe neutropenia that follows high-dose chemotherapy and autologous bone-marrow infusion by stimulating granulopoiesis. Filgrastim also increases numbers of circulating progenitor cells. We have studied the ability of filgrastim to mobilise peripheral-blood progenitor cells and assessed their efficacy when infused after chemotherapy on recovery of neutrophil and platelet counts. 17 patients with non-myeloid malignant disorders received filgrastim (12 micrograms/kg daily for 6 days) by continuous subcutaneous infusion. Numbers of granulocyte-macrophage progenitors in peripheral blood increased a median of 58-fold over pretreatment values, and numbers of erythroid progenitors increased a median of 24-fold. Three leucapheresis procedures collected a mean total of 33 (SEM 5.7) x 10(4) granulocyte-macrophage progenitors per kg body weight. 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. Platelet recovery was significantly faster in these patients than in controls who received the same treatment apart from the infusion of peripheral-blood progenitors; the platelet count reached 50 x 10(9)/l a median of 15 days after infusion of haemopoietic cells in the study patients compared with 39 days in controls (p = 0.0006). The accelerated neutrophil recovery associated with filgrastim treatment after chemotherapy was maintained. This method may be widely applicable to aid both neutrophil and platelet recovery after high-dose chemotherapy; it will allow investigation of peripheral-blood progenitor-cell allotransplantation.

Adolescent↗
PubMed1992

Prior chemotherapy does not prevent effective mobilisation by G-CSF of peripheral blood progenitor cells.

In this study we demonstrate that the hemopoietic growth factor, G-CSF successfully mobilised progenitor cell populations into the peripheral blood in a population of patients despite intensive pretreatment with chemotherapy. Administration of G-CSF increased the numbers of peripheral blood progenitor cells (PBPC) by a median of 76-fold above basal levels. Maximal levels of PBPC were observed on days 5 and 6 after G-CSF treatment. In two patients a second cycle of G-CSF mobilised PBPC to levels comparable with those seen after the first cycle of G-CSF treatment. An earlier hemopoietic cell population (pre-CFC's) was also mobilised with levels increased up to 50-fold above basal levels. Using a standard mononuclear cell leukapheresis technique the PBPC were collected extremely efficiently (essentially 100%) and could be further successfully enriched by separation using a Ficoll gradient. For patients who underwent the optimal collection protocol (i.e. leukapheresis on days 5, 6 and 7) a total of 32 +/- 6 x 10(4) GM-CFC kg-1 were collected. The ability to mobilise PBPC using G-CSF alone and to successfully and efficiently harvest these cells has important implications for the future of transplantation and high dose chemotherapy procedures.

Adolescent↗
PubMed1992

Studies of oral neutrophil levels in patients receiving G-CSF after autologous marrow transplantation.

Patients are at risk of mucositis and infections in the oral cavity during the neutropenic period after chemotherapy, which are significant causes of morbidity. In phase I/II studies with the haemopoietic growth factor granulocyte colony stimulating factor (G-CSF), a reduction in post-chemotherapy mucositis has been observed in addition to haematologic effects. To understand this phenomenon better in patients receiving G-CSF following high-dose chemotherapy with autologous bone marrow transplantation (ABMT), we studied the effects of G-CSF on levels of neutrophils recoverable from the oral cavity using a quantitative mouthrinse assay. In normal subjects, mouthrinses contained 472 +/- 329 x 10(3) neutrophils/mouthrinse. After chemotherapy followed by ABMT, mouthrinse neutrophil levels decreased to undetectable levels during the neutropenic period, but recovered 1-2 and 3-9 d before circulating neutrophil levels reached 0.1 and 1 x 10(9)/l respectively, whether or not patients received G-CSF. In patients who received G-CSF, the mean cumulative mucositis score was reduced from 35 +/- 9 to 21 +/- 12 (P < 0.05), and the maximum mean daily mucositis score was reduced from 2.8 +/- 0.5 to 1.7 +/- 0.9 (P < 0.01), compared to patients who did not receive G-CSF after ABMT. These studies provide in vivo evidence that neutrophils produced during G-CSF therapy are available to leave the circulation and enter tissues where their function is required for host defence. Since the usual temporal relationship between oral and peripheral blood neutrophil recovery was preserved during G-CSF administration after ABMT, these data support the hypothesis that the reduction in post-ABMT mucositis observed with G-CSF therapy may reflect a beneficial effect of G-CSF on the kinetics of oral mucosal neutrophil recovery in addition to the effect of G-CSF to accelerate peripheral blood neutrophil recovery.

Adolescent↗
PubMed1992

The definition of refractoriness to platelet transfusions.

The relationship between the 1 and 20 h post-transfusion platelet count and three parameters used to define refractory transfusions, namely the corrected increment (CI), platelet increment (PI), and percentage platelet recovery (%REC), was studied in 437 non-HLA matched platelet transfusions given to 102 patients with bone marrow failure. The percentage agreement between common definitions of refractoriness was calculated based on these parameters. As the maintenance of platelet counts above 20 x 10(9)/l is a relevant clinical goal for platelet support, the values of the CI, PI and %REC, which best corresponded to 1- and 20-h post-transfusion counts of 20 x 10(9)/l, were identified. A 1-h post-transfusion CI < 3 (PI < 7 x 10(9)/l or % REC < 8%) corresponded to clinically unsuccessful transfusions with a 1-h platelet count < 20 x 10(9)/l. A 1-h CI > or = 5.5 (PI > or = 12 x 10(9)/l or %REC > or = 14%) corresponded to clinically successful transfusions with a 20-h post-transfusion count of > or = 20 x 10/l. These data tie together the end points reported in the literature for defining refractory transfusions.

Blood Platelets↗
PubMed1992

Radiation-free preparation for allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia.

PURPOSE: The study was undertaken to investigate the effectiveness of allogeneic bone marrow transplantation from HLA-identical siblings after preparation with busulfan and cyclophosphamide in adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Thirty-nine patients aged 15 to 42 years underwent transplantation at three different centers from November 1984 through November 1990. All patients received 16 mg/kg busulfan and 120 mg/kg cyclophosphamide as preparative therapy. Cyclosporine plus methotrexate or cyclosporine plus corticosteroids with or without methotrexate were given for prevention of graft-versus-host disease (GVHD). RESULTS: Twelve patients died of treatment-related complications, 12 patients relapsed, and 15 patients are leukemia-free survivors. For 27 patients in group 1 (first remission, second remission, first relapse), the estimated leukemia-free survival (LFS) rate is 42.3% (95% confidence interval [CI], 22.9% to 71.7%) at 3 years. For 12 patients with more advanced disease (group 2), the 1-year LFS rate is 13.5% (95% CI, 0% to 37.1%). Chronic GVHD occurred at an estimated incidence of 63.3% and developed significantly more frequently among patients who received corticosteroids for prevention of acute GVHD. Chronic GVHD was associated with a significantly lower incidence of relapse and with improved LFS rates. CONCLUSION: LFS rate in this study is comparable to that obtained with radiation-containing regimens; however, the effectiveness of this preparative regimen in ALL requires further study.

Actuarial Analysis↗
PubMed1991

Treatment for acute myelocytic leukemia with allogeneic bone marrow transplantation following preparation with BuCy2.

One hundred twenty-seven patients with acute myelocytic leukemia (AML) were given busulfan 4 mg/kg on each of 4 days and cyclophosphamide 60 mg/kg on each of 2 days (BuCy2) followed by allogeneic bone marrow transplantation from an HLA-identical or one antigen disparate sibling. For 71 patients in first complete remission, 23 in second complete remission or initial relapse, and 33 patients with primary refractory disease, second or subsequent relapse, or a preceding hematologic disorder, the 3-year leukemia-free survival (LFS) is 63.1%, 32.6%, and 24.2% respectively. The actuarial probability of relapse for each group is 14.1%, 40.6%, and 61.0%. In multivariate analyses, relapse and decreased LFS were associated with advanced disease phase and with M4/M5 French-American-British classification. The LFS of first remission patients was adversely associated with a short time interval from diagnosis to transplantation. This study indicates that BuCy2 is an attractive preparative regimen for marrow transplantation in patients with AML and that prognostic factors for relapse and LFS are similar those described for regimens containing total body irradiation.

Adult↗
PubMed1991

Factors influencing 20-hour increments after platelet transfusion.

The 20-hour posttransfusion platelet count determines transfusion policy for patients requiring platelet support, and yet factors influencing the 20-hour count have been poorly defined. The clinical factors influencing both the 1- and 20-hour corrected count increment (CCI), were studied in 623 human leukocyte antigen (HLA)-unmatched platelet transfusions in 108 patients. The 1- and 20-hour CCIs were highly correlated (r = 0.67, p less than 0.001). On average, the 20-hour CCI was 64 percent of the 1-hour CCI. Multiple linear regression analyses identified splenectomy, bone marrow transplantation, disseminated intravascular coagulation, administration of amphotericin B, palpable spleen, and HLA antibody grade as the major factors influencing the 20-hour posttransfusion CCI. Platelet-specific antibodies, number of concurrent antibiotics, clinical bleeding, and temperature did not significantly influence the 20-hour posttransfusion CCI. The 1-hour CCI was the only significant factor influencing the 20-hour CCI in a regression model containing the 1-hour CCI and the above factors. Thus, the same clinical factors exert a major influence on the CCI at both 1 and 20 hours after platelet transfusion, with no evidence that any factor has more influence at 20 hours after transfusion than at 1 hour.

Blood Platelets↗
PubMed1991

Treatment of acute promyelocytic leukaemia relapsing after allogeneic bone marrow transplantation with all-trans-retinoic acid: suppression of the leukaemic clone.

We describe the clinical experience of a male patient with acute promyelocytic leukaemia, relapsing after sex-mismatched allogeneic bone marrow transplantation and treated with all-trans-retinoic acid. Resolution of the coagulopathy was observed by day 7 of therapy. A complete remission was achieved by day 47 after a period of pancytopenia, dysplastic myeloid maturation and bone marrow hypocellularity with necrosis and fibrosis. Serial cytogenetic analyses revealed a progressive loss of the male leukaemic clone [46XY,t(15;17)] and emergence of normal female (donor) cells [46XX] which became completely dominant with remission. Adverse effects of all-trans-retinoic acid included bone pain and a prominent leucocytosis requiring leukaphereses and hydroxyurea therapy. All-trans-retinoic acid can induce complete remission of recurrent acute promyelocytic leukaemia following bone marrow transplantation. The data suggest that remission is due to differentiation and suppression of the leukaemic clone while allowing repopulation of the marrow with non-malignant cells.

Adult↗
PubMed1991

The toxicity of busulphan and cyclophosphamide as the preparative regimen for bone marrow transplantation.

The toxicity of the conditioning regimen of high dose busulphan (Bu) (16 mg/kg) and cyclophosphamide (Cy) (120 mg/kg) has been compared to cyclophosphamide (Cy) (120 mg/kg) and fractionated total body irradiation (TBI) 12-14 Gy. Since 1985, 67 patients have received conditioning of Bu and Cy for HLA-identical sibling bone marrow transplants. 166 patients have received Cy and TBI since 1981. Veno-occlusive disease of the liver occurred in 19% in the Bu-Cy group and was fatal in 1/12 cases, but only in 1.3% of Cy-TBI group (P less than 0.0005) and was fatal in 1/2. 30% of evaluable patients developed haemorrhagic cystitis in the Bu-Cy group and 14% in the Cy-TBI group (P = 0.008). A multiple logistic regression analysis demonstrated the preparative regimen as the only significant risk factor for the development of veno-occlusive disease or haemorrhagic cystitis. Interstitial pneumonia was diagnosed in 12/56 evaluable patients (21%) in the Bu-Cy group and was fatal in 75%. It occurred in 39/137 evaluable patients (28%) in the Cy-TBI group with a 54% case mortality. Within the Bu-Cy group, the incidence of veno-occlusive disease and haemorrhagic cystitis was similar in chronic myeloid leukaemia (CML) and acute leukaemia (AL) groups, but there was a significant (P = 0.003) incidence of interstitial pneumonia in the CML group 36% as compared to 7% in the AL group. Preparative regimen and age were significant risk factors in the development of interstitial pneumonia in patients with CML. A flexural and acral rash ranging from pigmentation to severe erosion was noted in the Bu-Cy group, but not in the Cy-TBI group. Thus, veno-occlusive disease, haemorrhagic cystitis and cutaneous changes were more common in patients receiving Bu-Cy. Interstitial pneumonia was more common in patients receiving Bu-Cy for CML than for AL.

Adolescent↗