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Deborah Thomas

Publications and source records attributed to Deborah Thomas.

62 records · Page 4Linked to original sources
PubMed2002

Recombinant human soluble tumor necrosis factor (TNF) receptor (p75) fusion protein Enbrel in patients with refractory hematologic malignancies.

PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) is an important effector and regulatory cytokine involved in the pathophysiology of hematologic malignancies, including hairy cell leukemia (HCL), chronic lymphocytic leukemia (CLL), agnogenic myeloid metaplasia (AMM) and Philadelphia-negative myeloproliferative disorders (MPD). We conducted a pilot study to assess the safety of the soluble TNF receptor, etanercept (p75 TNFR:Fc; Enbrel) in patients with refractory hematologic malignancies. METHODS: Patients were eligible if they had refractory HCL, CLL, AMM, or Philadelphia-negative MPD. Enbrel was administered twice weekly at a dose of 25 mg subcutaneously for a minimum of eight doses, and was continued in patients without overt progression. RESULTS: Among the 26 patients enrolled on study, 25 patients were evaluable. Nine patients had AMM, eight CLL, three HCL, and five Philadelphia-negative MPD. Their median age was 60 years (range 30-83 years). A total of 70 courses consisting of 486 doses of Enbrel were administered. Enbrel was well tolerated, without any overt increase in infectious episodes. Stable disease/no objective response was seen in 22 patients (88%) and progression in 3 patients (12%). Three patients with AMM improved (two showed hematologic improvement, and one showed a reduction in liver and spleen size), and two patients (one with CLL and one with Philadelphia-negative MPD) showed improvement in disease-related symptoms. CONCLUSIONS: Enbrel was well tolerated, but no responses were noted in these immunosuppressed patients with refractory hematologic malignancies.

Adult↗
PubMed2002

Simultaneous homoharringtonine and interferon-alpha in the treatment of patients with chronic-phase chronic myelogenous leukemia.

BACKGROUND: Homoharringtonine (HHT) has antileukemic activity in patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML). Combinations of HHT, interferon-alpha (IFN-alpha), and cytarabine (ara-C) have been studied in various CML phases. The objectives of this study were to evaluate the efficacy and toxicity profiles of a combination regimen of simultaneous HHT and IFN-alpha therapy in patients with chronic-phase CML who were not exposed previously to either agent. METHODS: Forty-seven patients were treated: 37 patients with early chronic-phase CML (2 patients with clonal evolution) and 10 patients with late chronic-phase CML. Their median age was 62 years (range, 23-73 years). HHT was given at a dose of 2.5 mg/m(2) by continuous intravenous infusion over 24 hours daily for 5 days every month, and IFN-alpha was given daily at a target dose of 5 x 10(6) units/m(2) subcutaneously. Response, survival, and treatment toxicity were analyzed. RESULTS: Overall, the complete hematologic response (CHR) rate was 85%; the cytogenetic response rate was 66%, with major cytogenetic responses (Ph positive in < 35% of metaphases) in 49% of patients and complete cytogenetic responses in 21% of patients. The CHR rate, cytogenetic response rate, and major cytogenetic response rate were 84%, 69%, and 52%, respectively, in patients with early chronic-phase CML. Among the 10 patients with late chronic-phase CML, the CHR rate, cytogenetic response rate, and major cytogenetic response rate were 80%, 50%, and 40%, respectively. Response rates in patients age > 60 years were 84%, 62%, and 49% for CHR, cytogenetic response, and major cytogenetic response. Myelosuppression was frequent but manageable: Anemia with hemoglobin < 8.0 g/dL occurred in 36% of patients, requiring dose adjustments and erythropoietin therapy. Nonhematologic toxicities were mainly fatigue, aches, and gastrointestinal disturbances. Dose reductions with multiple courses were significant and were due to myelosuppression: After 6-24 courses, the median daily IFN-alpha dose was 1 MU/m(2), and the median number of days on HHT per month was 2 days. With a median follow-up of 26 months, the estimated 2-year survival rate was 90% (95% confidence interval, 79-100%). CONCLUSIONS: The simultaneous combination of HHT and IFN-alpha is safe and effective, but the dose schedules that actually were delivered were significantly lower than the planned dose schedules. With the availability of signal-transduction inhibitor 571 (imatinib mesylate), studies of combination of HHT and IFN-alpha chemotherapy in patients with CML who have disease that fails to respond to imatinib mesylate and of combinations with imatinib mesylate need to be explored.

Adult↗
PubMed2002

Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia.

BACKGROUND: Patients with acquired immunodeficiency syndrome (AIDS)-associated lymphoma/leukemia have a poor prognosis and are frequently treated with low-intensity therapy. The authors investigated the feasibility and efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD), a dose-intensive chemotherapy regimen, in patients with AIDS-associated Burkitt lymphoma/leukemia, as well as the possible impact of highly active antiretroviral therapy (HAART) in these patients. METHODS: Thirteen patients with AIDS-associated Burkitt lymphoma (six patients) or leukemia (acute lymphoblastic leukemia; seven patients) were treated with hyper-CVAD alternating with high-dose methotrexate and ara-C for a total of eight cycles. Nine patients received HAART from the start of induction chemotherapy (seven patients) or later in the course of chemotherapy (two patients). The median patient age was 43 years (range, 32-55). Nine patients were diagnosed with human immunodeficiency virus (HIV) infection at the time of diagnosis of Burkitt lymphoma/leukemia; the other 4 patients had been diagnosed with HIV infection for a median of 37 months (range, 18-137) prior to the diagnosis of Burkitt lymphoma/leukemia. The median absolute CD4 count from the 9 patients with evaluable counts was 77 cells/microL (range, 9-544); only one patient had a count > 200/microL. RESULTS: Twelve patients (92%) achieved a complete remission (CR) and one achieved a partial response (PR). Eight patients continued in CR after a median of 31 months (range, 7-45) at the time of writing. Five patients were alive and in CR over two years later. The median survival was 12 months, with 48% of patients alive after 2 years. Six of seven patients who received HAART from the start of chemotherapy were alive and in CR after a median of 29 months (range, 7-45). The four patients who did not receive HAART died. The regimen was universally myelosuppressive, but the toxicity profiles, recoveries from myelosuppression, and incidences of infectious complications were similar to that of non-HIV patients with Burkitt lymphoma/leukemia treated with the same regimen. CONCLUSIONS: Hyper-CVAD is an effective regimen for patients with AIDS-associated Burkitt lymphoma/leukemia, with acceptable toxicity. The combination of hyper-CVAD and HAART is associated with long-term survival in patients with the two diseases, which, until recently, were both considered invariably fatal and almost futile to treat medically.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Central nervous system relapse in adults with acute lymphoblastic leukemia.

BACKGROUND: Recurrence of acute lymphoblastic leukemia (ALL) in the central nervous system (CNS) in adults is considered a poor prognostic feature. Few reports have analyzed this issue. The objective of this study was to analyze the experience with CNS recurrence in adult patients with ALL. METHODS: Between December 1982 and April 2000, the records of 527 consecutive, newly diagnosed patients with ALL who were treated at the M. D. Anderson Cancer Center were reviewed. Patients were treated with one of two published regimens: vincristine, doxorubicin, and dexamethasone (VAD; n = 237 patients) or hyperfractionated cyclophosphamide plus VAD (hyper-CVAD) (n = 290 patients). Among 439 patients (83%) who achieved complete remission (CR), 32 patients (7%) had a CNS recurrence. All patients had received CNS prophylaxis tailored to the risk of CNS recurrence with systemic chemotherapy with or without intrathecal (IT) chemotherapy; none received cranial radiotherapy for prophylaxis. The records of these patients were reviewed. RESULTS: The median age at the time of diagnosis was 33 years. The median CR duration prior to CNS recurrence was 36 weeks (range, 2-185 weeks). Three groups were identified: 1) patients with an isolated CNS recurrence (n = 17 patients), 2) patients with CNS recurrences after bone marrow (BM) recurrence (n = 8 patients), and 3) patients with simultaneous CNS and BM recurrences (n = 7 patients). IT chemotherapy was effective in achieving a CNS CR in 30 patients (94%), but 10 patients (31%) had a second CNS recurrence. The median survival from CNS recurrence was 6 months; 28% of patients were alive at 1 year, and 6% of patients were alive at 4 years. CONCLUSIONS: Adults with ALL and CNS recurrences have a poor prognosis despite effective IT chemotherapy. Future studies should investigate better approaches in the treatment of these patients to improve their long-term survival. Effective CNS prophylaxis remains the single best approach for treating patients with CNS leukemia.

Adolescent↗
PubMed2002

CD56 expression predicts occurrence of CNS disease in acute lymphoblastic leukemia.

We examined the pre-treatment bone marrow samples from 200 consecutive adult patients with acute lymphoblastic leukemia (ALL) treated on various protocols at the University of Texas, M.D. Anderson Cancer Center between 1986 and 1998. Standard MFC techniques were used to determine CD56 expression on the leukemia blasts cells. The expression of CD56 was correlated with clinical characteristics at diagnosis, response to therapy, survival and disease-free survival. Blast expression of CD56 (> or = 20% of leukemic blasts) was seen in 16 (8%) of patients, with a median expression of 67% (range 20-99%). CD56 expression was associated with a higher incidence of central nervous system (CNS) disease at diagnosis (19% versus 4%; P=0.016). Incidence of CNS disease at any time was higher in patients with CD56+ disease (31% versus 14%; P=0.057). Among the 109 patients uniformly treated with the hyperCVAD regimen, CD56 expression was associated with a statistically significant higher incidence of CNS disease (33% versus 9%; P=0.026). CD56 expression in ALL is uncommon but may predict a higher risk for CNS disease. If these results are confirmed, CD56 expression could be used in combination with other high-risk features (e.g. lactate dehydrogenase (LDH), S-phase fraction, mature B-cell phenotype) to design a risk-oriented approach to CNS prophylaxis.

Adolescent↗
PubMed2002

Differences in CD33 intensity between various myeloid neoplasms.

We measured the concentration of CD33 antigen on the surface of cells in 315 bone marrow (BM) samples and 114 corresponding peripheral blood (PB) samples from patients with various leukemias (acute myeloid leukemia [AML], chronic myelogenous leukemia [CML], myeloproliferative disorder [MPD] other than CML, myelodysplastic syndrome [MDS]) and from control subjects. Overall CD33 intensity in total CD33+ cells was significantly higher in BM than in PB. CD33 intensity in total BM CD33+ cells differed significantly with the type of disease. The median number of CD33 molecules per cell was highest in AML, followed by MDS, CML, and control subjects and lowest in MPD. When only CD34+/CD33+ cells were examined, CD33 molecules per cell were highest in CD34+ cells in AML and lowest in MPD (P = .027). Patients with AML or MDS younger than 60 years had significantly higher intensity of CD33 expression on CD34+ cells than patients 60 years or older. Levels of CD33 intensity did not correlate with cytogenetics in patients with AML or MDS. There was no correlation between CD33 intensity and response to therapy or overall survival in 35 patients treated with protocols including Mylotarg. These data demonstrate variation in CD33 intensity between various leukemias.

Aminoglycosides↗
PubMed2002

A phase I study of idarubicin dose escalation with amisfostine and high-dose cytarabine in patients with relapsed acute myelogenous leukemia and myelodysplastic syndromes.

BACKGROUND AND OBJECTIVES: Early studies have suggested that increasing doses of anthracycline improve outcome in younger patients with acute myelogenous leukemia (AML), but dose escalation has been precluded by the acute and chronic toxicities of these agents. Amifostine is a cytoprotective compound that has been shown to protect against the acute cytotoxicities of anthracyclines in animal models. We report the results of a phase I study of dose escalation of idarubicin with amifostine and high-dose ara-C in patients with relapsed or refractory AML or myelodysplastic syndrome (MDS). DESIGN AND METHODS: The continuous reassessment method was used to predict the probability of toxicity. RESULTS: Five patients were treated at an idarubicin dose of 18 mg/m2/day x 3, three of whom developed grade 3 diarrhea or mucositis. Subsequently, three additional patients were treated at a dose of 15 mg/m2 x 3 days, all of whom experienced grade 3 diarrhea or mucositis. One patient achieved complete remission (CR rate 12.5%, 95% CI 0-0.52%). INTERPRETATION AND CONCLUSIONS: The addition of amifostine does not allow dose escalation of idarubicin when combined with high-dose ara-C.

Adult↗