PubMed Health⌕ Search

Biomedical subjects

J Szer

Publications and source records attributed to J Szer.

At least 37 records · Page 2Linked to original sources
PubMed2003

Prior and concurrent administration of recombinant human megakaryocyte growth and development factor in patients receiving consolidation chemotherapy for de novo acute myeloid leukemia--a randomized, placebo-controlled, double-blind safety and efficacy study.

Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) administered after acute myeloid leukemia (AML) chemotherapy (CT) failed to shorten the time of transfusion-dependent thrombocytopenia in a previous study. In this multicenter, randomized, placebo-controlled, double-blind study we determined the effect of administration of PEG-rHuMGDF prior to CT and of administration prior, concurrent, and 1 day post CT on platelet recovery and transfusion requirements in patients receiving consolidation CT for de novo AML. Patients were randomized to receive either 30 microk/kg PEG-rHuMGDF as a single dose on day -6 ( n=37), placebo as a single dose on day -6 ( n=9), 30 microk/kg PEG-rHuMGDF administered on day -6 followed by 10 microg/kg on days -5 to day 6 (through CT and including the day after CT, n=35), or placebo administered on day -6 to day 6 ( n=9). The median times to transfusion-independent platelet recovery to >20x10(9)/l were 24.5 and 24.0 days in the PEG-rHuMGDF day -6 group and PEG-rHuMGDF day -6 to 6, respectively, compared to 21.0 days in the placebo group. There were no significant differences in the number of days of platelet transfusions between either PEG-rHuMGDF schedule or placebo. The PEG-rHuMGDF day -6 to 6 group had a delayed absolute neutrophil count (ANC) recovery compared to either placebo or PEG-rHuMGDF day -6 treated patients. Thus, alteration of the scheduling of PEG-rHuMGDF in terms of earlier dosing before and during chemotherapy did not improve platelet recovery but rather delayed hematopoietic reconstitution. Although unexpected, these observations may be of major relevance for the design of future clinical trials with recombinant thrombopoietins.

Adult↗
PubMed2003

The incidence, pathogenesis and natural history of steatorrhea after bone marrow transplantation.

A small number of case reports of steatorrhoea after allogenic BMT have been published, but the incidence and natural history of this complication have not been defined. We reviewed the incidence of steatorrhoea in 184 consecutive allograft recipients surviving at least 100 days. Steatorrhoea was documented in five patients, a median of 5.5 months (range 4-14) post-transplant. All patients had recent or concomitant acute gut or liver graft versus host disease (GVHD). The probability of developing steatorrhoea by 2 years post-transplant was 3.3% (95% confidence interval (CI) +/- 2.9% in the group overall, rising to 4.8% (CI +/- 4.2%) in patients with acute and/or extensive chronic GVHD. All patients responded clinically to pancreatic enzyme supplements. While these observations are consistent with previously reported autopsy data suggesting that GVHD of the exocrine pancreas is likely to be predominant underlying pathological process, in two patients concomitant small bowel or hepatic dysfunction may have contributed to the severity of steatorrhoea. Enzyme supplements were subsequently ceased in three patients without return of steatorrhoea, suggesting that the process is usually reversible. Our data demonstrate that steatorrhoea is not infrequent complication in the 2 years postallograft, particularly in patients with GVHD.

Adult↗
PubMed2003

Differences between graft product and donor side effects following bone marrow or stem cell donation.

We report graft product stem cell yields and donor safety results of a randomized multicenter study comparing allogeneic peripheral blood stem cell (PBSC) PBSC transplantation with BM transplantation. Matched HLA-identical sibling donors (n=329) were randomized to filgrastim-mobilized PBSC or bone marrow (BM) donation groups. Median yields per kg recipient weight of CD34(+) cells, T cells, and natural killer (NK) cells, respectively, were approximately two-fold, eight-fold, and greater than eight-fold in the PBSC group than in the BM group (CD34(+) cells, 5.8 x 10(6)/kg vs 2.7 x 10(6)/kg; T cells, 300.1 x 10(6)/kg vs 35.7 x 10(6)/kg; NK cells, 28.2 x 10(6)/kg vs 3.6 x 10(6)/kg; P<0.001 for each). In connection with the cell collection procedures, PBSC donors spent a shorter median time in hospital than BM donors (0 vs 2 days; median difference -2 days, 95% CI -2 to 2) and had fewer median days of restricted activity (2 vs 6 days; median difference -3 days, 95% CI -4 to 2). Overall, 65% of PBSC donors and 57% of BM donors reported at least one adverse event (AE), most of which were transient, mild-moderate in severity, and without clinical sequelae. PBSC donors experienced predominantly filgrastim-related AEs, while BM donors experienced predominantly harvest-related AEs.

Adolescent↗
PubMed2003

Morphological effects of imatinib mesylate (STI571) on the bone marrow and blood of patients with Philadelphia chromosome (Ph) positive chronic myeloid leukaemia.

There have been few reports on the morphological findings in patients with chronic myeloid leukaemia (CML) undergoing treatment with imatinib mesylate. We examined morphological changes in the marrow and peripheral blood of 27 patients with chronic phase (CP), accelerated phase (AP) and blastic phase (BP) CML, 3 and 6 months after treatment with imatinib. At 3 months there was a significant clearance of leukaemic cells as evidenced by a complete haematological response (CHR) in the peripheral blood in 25 patients, together with reduced marrow cellularity in 25 (median reduction CP 42%; AP/BP 68%) and a reduction in the number of megakaryocytes (13 of 18 CP: five of six AP/BP; three patients did not have an assessable marrow) with an increase in the amount of normal megakaryopoiesis. After 6 months, there was continued morphological improvement in eight of 17 CP patients (one patient died after 3 months) with continued cytogenetic response (7 out of 15 patients with assessable metaphases had no abnormal Ph+ cells and three had <35% Ph+ cells) and maintenance of haematologic response in all patients. After an initial response to treatment at 3 months in the AP/BP group, with CHR and a reduction in cellularity in all patients, we found morphological evidence of a loss of response to treatment, with an increase in leukaemic cells, as evidenced by loss of CHR in three of nine and an increase in median cellularity in five patients. No patient in this group achieved a complete cytogenetic response. In summary, in CML-CP patients treated with 6 months of imatinib, there was a significant reduction in leukaemic cells as evidenced by a haematolological response in the peripheral blood, together with reduced marrow cellularity, restoration of morphologically normal haemopoiesis and a meaningful cytogenetic response. Maintaining a response to treatment appeared less likely to occur in the AP/BP group patients, especially those who did not achieve any cytogenetic response to treatment.

Antineoplastic Agents↗
PubMed2002

A phase I dose-escalation study of etoposide continuous infusion added to busulphan/cyclophosphamide as conditioning prior to autologous or allogeneic stem cell transplantation.

Relapse of the primary disease remains the predominant cause of death following bone marrow transplantation for high-risk haematological malignancies. Improved supportive care and patient selection have resulted significant improvements in toxicity with standard conditioning regimens. Further dose intensification to reduce the risk of relapse may therefore be feasible. We determined the maximal tolerated dose (MTD) of a 5-day continuous infusion (CI) of etoposide when added to oral busulphan 16 mg/kg and intravenous cyclophosphamide 120 mg/kg (Bu/Cy) as conditioning in 44 autograft and 18 allograft recipients at high risk of relapse. The major toxicity of escalating doses of etoposide was oral and gastro-intestinal mucositis, reflected by a statistically significant increase in the requirement for total parenteral nutrition in both autografts and allograft recipients. Time to neutrophil and platelet recovery, opiate analgesia requirements, and duration of hospitalization were not affected by etoposide dose escalation. The MTD in autograft recipients was 300 mg/m(2)/day (1500 mg/m(2) total dose), and 100 mg/m(2)/day (500 mg/m(2) total dose) for allograft recipients. Mucositis and hepatotoxicity were more frequent in allograft recipients, suggesting that methotrexate may have contributed to the lower tolerable dose in these patients. As a consequence, further dose escalation may not be possible in heavily pre-treated patients undergoing allogeneic transplantation. Conversely, high dose CI etoposide can be added with relative safety to Bu/Cy in autograft recipients.

Adolescent↗
PubMed2002

Sequential transformation of t(8;13)-related disease: a case report.

We report a case of an atypical myeloproliferative disorder with t(8;13) that presented as B-lineage acute lymphoblastic leukaemia (B-ALL). Following induction chemotherapy, the disease manifested as chronic myeloproliferative state, which responded to hydroxyurea. Terminally, the disease transformed into acute myeloid leukaemia (AML) with additional chromosomal abnormalities including monosomy 7. To our knowledge, this is the first case of this rare atypical myeloproliferative disorder with t(8;13) that presented as B-ALL and terminally transformed to AML with additional chromosomal abnormalities.

Acute Disease↗
PubMed2001

Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is characterized by formation of the BCR-ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. Large deletions on the derivative chromosome 9 have recently been reported, but it was unclear whether deletions arose during disease progression or at the time of the Ph translocation. Fluorescence in situ hybridization (FISH) analysis was used to assess the deletion status of 253 patients with CML. The strength of deletion status as a prognostic indicator was then compared to the Sokal and Hasford scoring systems. The frequency of deletions was similar at diagnosis and after disease progression but was significantly increased in patients with variant Ph translocations. In patients with a deletion, all Ph(+) metaphases carried the deletion. The median survival of patients with and without deletions was 38 months and 88 months, respectively (P =.0001). By contrast the survival difference between Sokal or Hasford high-risk and non-high-risk patients was of only borderline significance (P =.057 and P =.034). The results indicate that deletions occur at the time of the Ph translocation. An apparently simple reciprocal translocation may therefore result in considerable genetic heterogeneity ab initio, a concept that is likely to apply to other malignancies associated with translocations. Deletion status is also a powerful and independent prognostic factor for patients with CML. The prognostic significance of deletion status should now be studied prospectively and, if confirmed, should be incorporated into management decisions and the analysis of clinical trials.

Adult↗
PubMed2001

Fludarabine and mitoxantrone: effective and well-tolerated salvage therapy in relapsed indolent lymphoproliferative disorders.

BACKGROUND: Prior studies of the combination of fludarabine, mitoxantrone and dexamethasone have yielded high response rates but are associated with a significant risk of opportunistic infections, predominantly Pneumocystis Carinii pneumonia (PCP) requiring routine prophylaxis. PATIENTS AND METHODS: We evaluated the combination of fludarabine (25 mg/m2/day x 3) and mitoxantrone (10 mg/m2 x 1) without corticosteroids or PCP prophylaxis in 29 patients with relapsed or refractory indolent lymphoproliferative disorders; median age 56 years, 62% refractory to preceding chemotherapy. RESULTS: A median of four cycles was administered without cumulative myelosuppression. Neutropenia <0.5 x 10(9/)l was seen in 16% of cycles. Infections complicated 10.4% of cycles. with impaired performance status (> or = ECOG 2) and increased age ( > 56 years) significant risk factors (P < or = 0.01). No cases of PCP were encountered. The response rate was 90%, median remission duration 11.9 months and the median survival 57 months. Peripheral blood progenitor cell mobilization was attempted in 11 patients and yielded > or = 2 x 10(6) CD34+ cells/kg in only 5 cases (45%). CONCLUSIONS: High response rates can be attained with fludarabine and mitoxantrone in combination without corticosteroids, and routine PCP prophylaxis can safely be omitted. Peripheral blood progenitor collections are problematic in these heavily pretreated patients.

Adult↗
PubMed2001

Allogeneic haemopoietic cell transplants in Australia, 1996--a multi-centre retrospective comparison of the use of peripheral blood stem cells with bone marrow.

A retrospective comparison was carried out on adult patients receiving HLA-identical allogeneic haemopoietic stem cell transplants from siblings in Australia in 1996, comparing bone marrow with G-CSF-mobilised peripheral blood stem cells. A total of 131 transplant recipients from nine centres were included in this study, of whom 79 received bone marrow, 44 blood stem cells and eight both. All but three of the 131 patients had cyclosporin and methotrexate as graft-versus-host disease prophylaxis. The minimum follow-up time for surviving patients is 27 months. Comparisons were carried out between the BM and PBSC groups. There were no significant differences between groups in age, sex, diagnosis, donor characteristics or pretransplant conditioning. Median time to neutrophil recovery of 0.5 x 10(9)/l was 14 days for PBSC recipients, compared to 19 days for marrow recipients (P < 0.0005). median time to platelet recovery of 20 x 10(9)/l was 17 days for PBSC recipients, compared to 28 days for marrow recipients (P < 0.0005). there were no significantly increased risks of either acute or chronic GVHD in the PBSC recipients. there were no significant differences between the groups in the incidence of major transplant-related complications, disease-free survival or overall survival.

Adolescent↗
PubMed2001

Acute left ventricular failure following melphalan and fludarabine conditioning.

Cardiotoxicity has rarely been reported as a complication of melphalan or fludarabine administration as single agents. Recently, melphalan and fludarabine have been used in combination as non-myeloablative conditioning chemotherapy prior to allogeneic stem cell transplantation. We have observed the development of severe left ventricular failure in three of 21 patients treated with this combination. Cardiotoxicity in this context has not previously been reported and has implications for the assessment, monitoring and treatment of patients undergoing pre-transplant conditioning with melphalan and fludarabine.

Acute Disease↗
PubMed2001

Abnormal cervical cytology in bone marrow transplant recipients.

Particular human papillomavirus (HPV) subtypes are implicated in the genesis of abnormal cervical cytology and cervical cancer. While most immunocompetent hosts clear HPV infection with no sequelae, some develop premalignant cytological changes of whom a minority subsequently progress to overt carcinoma. Immunocompromised patients, such as renal allograft recipients and HIV-infected individuals, have a higher rate of cytological abnormalities. This is thought to be due to prolonged persistence of virus due to impaired clearance by the immune system. We undertook a retrospective review of the cervical cytology of all women who underwent BMT at two transplant centres and who had cervical smears performed between 1990 and 1998. The rate of cytological abnormalities was significantly higher than in the general population before BMT (age-adjusted odds ratio (OR) 2.2, P = 0.02) and after BMT (OR 7.0, P < 0.0001). After BMT, allogeneic recipients had a higher rate of abnormalities than did autologous patients (OR 2.6, P = 0.02) although only allogeneic recipients had a higher rate of abnormalities post-BMT compared to pre-BMT (allogeneic OR 6.8, P = 0.004). These observations suggest that pre-transplant disease and treatment factors increase the risk of cytologic abnormalities and that transplant-related factors such as conditioning therapy and immunosuppression further increase this risk. These data suggest that more frequent screening may be required in these at-risk groups, especially allogeneic recipients. Prospective studies are required to further evaluate cytological abnormalities and HPV shedding in these populations.

Adult↗
PubMed2001

Patterns of failure with increasing intensification of induction chemotherapy for acute myeloid leukaemia.

Patterns of failure were studied in two consecutive randomized trials of intensified induction therapy carried out by the Australian Leukaemia Study Group (ALSG) between 1984 and 1991 to determine the impact of dose intensification. Patients received standard dose cytarabine and daunorubicin (7-3), 7-3 plus etoposide (7-3-7) or 7-3 plus high-dose cytarabine (HIDAC-3-7) chemotherapy. Patients with FAB M3 morphology were excluded. Time to failure (TTF) was defined as the time from randomization to induction death or removal from study for non-responders, or to relapse or death in complete response (CR) for complete responders. An estimated 86% of 470 de novo patients with acute myeloid leukaemia failed within 10 years of randomization, as a result of death in induction in 17% of the randomized patients, failure to achieve CR in a further 17%, relapse in 44% and death in CR in 8% of patients. An estimated 66% of patients failed as a result of refractory disease or relapse within that period (disease-related failures). Multifactor analysis identified age and peripheral blast count as the most significant pretreatment factors associated with overall TTF. These factors, together with cytogenetics, were significantly associated with disease-related failures. High-dose cytarabine in induction significantly decreased the disease-related failure rate as did allogeneic transplantation in first CR. The impact of high-dose cytarabine did not depend on the cytogenetic risk group.

Acute Disease↗
PubMed2001

Atypical retinal microvasculopathy after bone marrow transplantation.

OBJECTIVE: Typical early ischaemic retinal microvascular changes with cotton wool spots after allogeneic bone marrow transplantation (BMT) are well recognised. In the study an atypical non-ischaemic late retinopathy is described. METHODS: Sequential cases of late retinal microvasculopathy following allogeneic BMT were reviewed. Demographic features and clinical and angiographic data were collected. RESULTS: Of 399 patients undergoing allogeneic BMT between 1992 and 1999, eight eyes of four patients developed atypical retinopathy. All patients were male and the age range was 27-50 (mean 37.5) years. The indications for BMT were acute lymphoblastic leukaemia (two patients), chronic myeloid leukaemia (one patient) and chronic lymphocytic leukaemia (one patient). Two patients had conditioning regimens including irradiation. All had cyclosporine and methotrexate as graft-versus-host disease prophylaxis. All but one had cyclophosphamide and busulphan as conditioning treatment. One had interferon. No patients had sustained hypertension or diabetes mellitus. Atypical retinopathy was identified 13-62 (mean 50) months after BMT and clinical features consisted of microaneurysms (MA; 4/4), hard exudates (1/4) and macular oedema (1/4). No patient had cotton wool spots. The median acuity was 6/5. Angiographic features were MA (4/4), late leak (2/4) and peripheral (1/4) or central (1/4) ischaemia. One patient underwent focal photocoagulation for macular oedema. CONCLUSION: Retinal microvascular incompetence (without cotton wool spots) with good vision may occur in a small number of patients as a late complication of allogeneic BMT

Adult↗
PubMed2001

Pain language of bone marrow transplantation patients.

Previous studies have shown that hypnosis may be effective in reducing intensity of pain among bone marrow transplantation patients whereas cognitive behavioral intervention without imagery was not effective for this group of patients. Since hypnosis alters patients' perception of pain and cognitive behavioral intervention changes patients' beliefs and improves their coping with pain, we hypothesized that sensory pain is more important than affective pain in understanding the pain experience of patients undergoing bone marrow transplantation. To test this hypothesis we administered the McGill Pain Questionnaire longitudinally to 50 consecutive eligible recipients of bone marrow transplantation during hospitalization to assess the different dimensions of pain they experienced. Consistent with our hypothesis, sensory pain fluctuated with treatment stages, and the pattern was consistent with previous findings. Patients reported significantly higher sensory pain than affective pain at all assessment points. In contrast, affective pain remained low and stable throughout the treatment. Our results contribute to the understanding of the nature of pain in bone marrow transplantation and suggest pain management strategies that focus on sensory pain as in hypnosis are more useful for such patients.

Adaptation, Psychological↗