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J M Rowe

Publications and source records attributed to J M Rowe.

At least 73 records · Page 4Linked to original sources
PubMed1997

Long-term survival in acute myeloid leukemia: the Eastern Cooperative Oncology Group experience.

BACKGROUND: The data base of the Eastern Cooperative Oncology Group (ECOG) provides access to data on a large adult patient population drawn from more than 25 major university institutions and hundreds of participating hospitals. Extensive medical files are maintained at the ECOG Coordinating Center and are updated regularly. METHODS: Data on 1414 eligible patients with acute myeloid leukemia (AML), treated on 6 ECOG protocols during the period 1976-1994, were reviewed to determine the number of long-term survivors (LTS) and to identify factors that predicted LTS. Disease free survival and factors impacting quality of life were examined as well. RESULTS: Of the 1414 patients, 274 survived for > or = 3 years and were considered LTS. A logistic regression analysis revealed that factors predicting LTS included age < 55 years, female gender, treatment between 1985 and 1990, white blood cell count < 10,000 cells/mm3, and hemoglobin > 10 g/dL. Disease free survival improved with escalating intensity of therapy. Quality-of-life data showed that infections were fairly common. Significant graft-versus-host disease occurred in 6 of 40 patients who received allogeneic bone marrow transplantation and contributed to the deaths of 4 individuals. Information on employment, insurance, social or marital difficulties, and psychosocial issues was more difficult to obtain. CONCLUSIONS: Prognosis in AML is a complex interaction involving the cellular origin of the malignant clone, morphology, and evolving therapeutic strategies. The most recent ECOG studies incorporate these variables and should provide additional insights into factors affecting LTS in patients with AML.

Acute Disease↗
PubMed1997

All-trans-retinoic acid in acute promyelocytic leukemia.

BACKGROUND: All-trans-retinoic acid induces complete remission in acute promyelocytic leukemia. However, it is not clear whether induction therapy with all-trans-retinoic acid is superior to chemotherapy alone or whether maintenance treatment with all-trans-retinoic acid improves outcome. METHODS: Three hundred forty-six patients with previously untreated acute promyelocytic leukemia were randomly assigned to receive all-trans-retinoic acid or daunorubicin plus cytarabine as induction treatment. Patients who had a complete remission received consolidation therapy consisting of one cycle of treatment identical to the induction chemotherapy, then high-dose cytarabine plus daunorubicin. Patients still in complete remission after two cycles of consolidation therapy were then randomly assigned to maintenance treatment with all-trans-retinoic acid or to observation. RESULTS: Of the 174 patients treated with chemotherapy, 120 (69 percent) had a complete remission, as did 124 of the 172 (72 percent) given all-trans-retinoic acid (P=0.56). When both induction and maintenance treatments were taken into account, the estimated rates of disease-free survival at one, two, and three years were 77, 61, and 55 percent, respectively, for patients assigned to chemotherapy then all-trans-retinoic acid; 86, 75, and 75 percent for all-trans-retinoic acid then all-trans-retinoic acid; 75, 60, and 60 percent for all-trans-retinoic acid then observation; and 29, 18, and 18 percent for chemotherapy then observation. By intention-to-treat analysis, the rates of overall survival at one, two, and three years after entry into the study were 75, 57, and 50 percent, respectively, among patients assigned to chemotherapy, and 82, 72, and 67 percent among those assigned to all-trans-retinoic acid (P= 0.003). CONCLUSIONS: All-trans-retinoic acid as induction or maintenance treatment improves disease-free and overall survival as compared with chemotherapy alone and should be included in the treatment of acute promyelocytic leukemia.

Adolescent↗
PubMed1997

S-HAM induction chemotherapy with or without GM-CSF in patients with high-risk myelodysplastic syndromes.

Thirty-one adult patients with high-risk myelodysplastic syndromes (MDS) were enrolled in a prospective randomized double-blind placebo-controlled trial evaluating the efficacy of sequential high-dose Ara C/mitoxantrone chemotherapy with or without GM-CSF. GM-CSF or placebo was given subcutaneously once daily at a dose of 250 micrograms/m2 starting 48 h prior to chemotherapy and continued until neutrophil recovery. This design allowed us to investigate the role of GM-CSF as a priming factor for the leukemic clone, as well as its effect on the recovery of normal hematopoiesis. Twenty-eight patients are currently evaluable for response. The patients reached a complete remission (36%), eight patients had persistent MDS (29%), and ten patients died within 6 weeks after the onset of treatment (early death). Infectious complications during cytopenia were the major cause of death (8/10). Median time to complete hematologic recovery (neutrophils > 500/microliter and platelets 20,000/microliter) and time to neutrophil recovery above 1500/microliter was 29 and 35 days, respectively. Median remission duration was 190 days (6.4 months). Analysis of prognostic subgroups showed a low CR rate (25%) and a high early-death rate (44%) in patients > 55 years of age, suggesting that the intensified treatment approach should be limited to younger patients. No data concerning the influence of GM-CSF on response to chemotherapy or duration of neutropenia are presently available.

Adult↗
PubMed1997

Prevention and treatment of acute graft-versus-host disease: the old and the new. A report from the Eastern Cooperative Oncology Group (ECOG).

There have been many advances in the prevention and treatment of GVHD, including cyclosporine, FK506, and combination therapies. This syndrome, however, continues to account for significant morbidity and mortality after allogeneic transplantation. With the expanded use of matched unrelated as well as mismatched related donors, the increase in incidence and severity of GVHD poses a new clinical challenge. Many of the newer agents discussed in this paper may have a role in the future as therapy for acute GVHD. The evaluation of these new agents and the approach to be taken is hampered by the realization that most patients have received and are relatively refractory to standard therapies. Clinical trials must be performed earlier in the course of the syndrome to establish the role of these compounds. Newer strategies are likely to include the use of sequential therapy directed at blocking endogenous cytokines followed by blocking alloreactive donor cells, and immunologic advances such as the induction of tolerance. What impact, if any, such therapy may have on amelioration of a graft-versus-leukemia effect remains unknown.

Acute Disease↗
PubMed1997

Autotransplantation for relapsed or refractory non-Hodgkin's lymphoma (NHL): long-term follow-up and analysis of prognostic factors.

One hundred and thirty-six patients autografted for relapsed or refractory non-Hodgkin's lymphoma (NHL) were evaluated to assess long-term event-free survival and to identify important prognostic factors. High-dose therapy consisted primarily of carmustine (BCNU), etoposide, cytarabine, and cyclophosphamide (BEAC) followed by unpurged autologous stem cell rescue. The 5-year Kaplan-Meier event-free survival (EFS) for the entire cohort was 34% (95% confidence interval: 24-44%) with a median follow-up of approximately 3 years (range 0-7.5 years). For patients entering with minimal disease (defined as all areas < or = 2 cm), the 5-year EFS was 40 vs 26% for those entering with bulky disease (P = 0.0004). In the multivariate analysis, minimal disease on entry and administration of involved-field XRT post-transplant were significantly associated with improved EFS; the latter association was observed mainly in the cohort of patients with bulky disease. The overall 100-day treatment-related mortality rate was 4.4% (3% for the last 71 patients). New strategies are needed to reduce the high rate of relapse (50-60%) following auto-transplantation for relapsed or refractory NHL.

Adolescent↗
PubMed1997

Hematopoietic growth factors in acute leukemia.

The hematopoietic growth factors are glycoproteins that can be produced by recombinant DNA technology. They have many potential clinical uses in acute leukemia; several areas have been explored extensively and much data are available from clinical trials. Other areas are of potential interest, but have a paucity of clinical information. The past decade has seen major strides in the development and clinical application of cytokines in acute leukemia and it is expected that this trend will continue over the next decade as further areas are explored and results of clinical trials mature to enable us to determine the precise role of cytokines in the clinical setting.

Clinical Trials as Topic↗
PubMed1997

Expression of CD25 (interleukin-2 receptor alpha chain) in adult acute lymphoblastic leukemia predicts for the presence of BCR/ABL fusion transcripts: results of a preliminary laboratory analysis of ECOG/MRC Intergroup Study E2993. Eastern Cooperative Oncology Group/Medical Research Council.

Of 144 adult Eastern Cooperative Oncology Group (ECOG) patients with acute lymphoblastic leukemia (ALL) entered on study E2993 at the time of analysis, 104 had informative immunophenotypes and molecular analysis by polymerase chain reaction for BCR/ABL fusion transcripts. In 23 patients (22%), BCR/ABL transcripts were detected: the ALL-typical e1a2 alone in 12, e1a2 + b2a2/b3a2 in five, and b2a2 and/or b3a2 in six. Of BCR/ABL-positive patients, 83% had early pre-B ALL, one patient had pre-T ALL, while half of the BCR/ABL-negative patients had early pre-B ALL, 18% had CD10-negative pro-B ALL and 21% were pre-T. When antibodies to both the interleukin-2 receptor alpha (CD25) and beta chain (CD122) were tested, CD25 was expressed significantly more frequently in BCR/ABL-positive (median 23% positive blast cells, range 1-84%) than BCR/ABL-negative patients (median 3%, range 0-69%) (P = 0.00006). There was no corelation with CD122 expression. Therefore, CD25 expression may serve as a surrogate marker for BCR/ABL positivity (Philadelphia chromosome), the major poor prognostic parameter in adult ALL.

Adult↗
PubMed1997

Economic analyses of phase III cooperative cancer group clinical trials: are they feasible?

Both economic and clinical evaluations of new pharmaceutical agents are important to physicians who practice in the current health care environment. While cooperative cancer groups carry out large-scale phase III clinical evaluations of these agents, few cooperative group studies incorporate economic analyses because of concerns over overburdening of data management, investigators, and statistical center personnel. In this study, we describe the results and operational considerations of one of the first completed economic analyses of a phase III cooperative group trial of the Eastern Cooperative Oncology Group (ECOG). We developed an economic model estimating economic benefits of yeast-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjunct therapy for adult patients (56-70 years) with acute myelogenous leukemia. Clinical data were based on prospectively collected information from a recently reported double-blind phase III multi-institutional study carried out by ECOG. Retrospective economic data were obtained from financial information systems at our hospital, one of the study sites. The cost-minimization analyses were based on the perspective of a third-party payer. Indirect costs related to loss of earnings by patients and caregivers as well as quality-of-life adjustments were not incorporated into the model. Clinical trial results indicated that patients treated with GM-CSF had shorter times to recovery of absolute neutrophil count of 500 cells/mm3 and 1000 cells/mm3 and fewer serious infections than patients who received placebo following induction chemotherapy, while no significant differences were noted in red blood cell and platelet transfusion dependency, toxicities, and duration of hospitalization. The economic model estimated that the group treated with GM-CSF was estimated to have lower costs of care, associated with lower frequencies of serious infections and lower overall infection-related costs. Sensitivity analyses indicated that these results held true over a wide range of estimates of costs and infection rates. Prospective economic analyses of phase III cooperative cancer group clinical trials have not been completed to date. Strategies that are not likely to overburden data managers and statistical center personnel are possible to devise. However, these studies require careful planning and coordination between clinical trialists, economists, and health services researchers.

Adult↗
PubMed1997

Bone marrow transplantation in first remission.

The allogeneic bone marrow transplant experience for acute myeloid leukemia (AML) is broader than that for acute lymphocytic leukemia (ALL). However, data describing disease-free survival in AML in first remission in the range of 40% to 65% are almost identical to the data from larger studies of ALL in first remission. Similarly, the published allogeneic transplant data for ALL in second remission are comparable to those in the AML experience. The efficacy of autologous stem-cell transplantation for ALL, while promising, remains unproven in first remission, and larger multicenter studies are underway to answer this question. Until prospective randomized trials of bone marrow or peripheral-blood stem-cell purging have been performed, a conclusion that ex vivo bone marrow transplantation is of clinical benefit for any patient with ALL will be impossible. Such studies will be difficult to conduct and, in an autologous setting, should include genetic marking to help determine whether reinfused leukemic cells will lead to relapse.

Bone Marrow Purging↗
PubMed1996

Treatment of the neutropenia of Felty syndrome.

This review sets out to synthesize and critically evaluate the current reported data regarding therapeutic options for the neutropenia associated with Felty syndrome (Felty neutropenia). A MEDLINE search and bibliographies from recent reviews were used to identify trials and case reports that provided sufficient data to evaluate the effect of various interventions on both the neutropenia and the clinical course of patients with Felty syndrome. Data were obtained on baseline hematologic profiles, bone-marrow biopsies, and patient characteristics; length of follow-up; hematologic and clinical responses to the various interventions; and side-effect profiles. Treatment with hemopoietic growth factors or methotrexate can produce sustained hematologic and clinical responses with an acceptable side-effect profile. Splenectomy produces a long-term hematologic response in 80% of patients. Patients who do not respond hematologically have a higher incidence of non-fatal infections, but a significant minority (46%) do not experience any infections; the incidence of fatal infections is 12%, regardless of whether a hematologic response occurs. Of the patients who had infections prior to surgery, 55% did not experience further infections after splenectomy. Initial treatment of Felty neutropenia should consist of hemopoietic growth factors because of their rapid onset of action and relatively low incidence of side-effects. Splenectomy is a reasonable option if growth factors are ineffective and rapid amelioration of neutropenia is needed. Methotrexate offers a potentially promising alternative for the treatment of both the rheumatologic and the hematologic manifestations of Felty syndrome.

Felty Syndrome↗
PubMed1996

Treatment and prognostic factors in acute myeloid leukaemia.

Current induction chemotherapy regimens afford a complete remission in 60 to 80% of patients less than 60 years of age who are diagnosed with acute myelogenous leukaemia. Patients who undergo consolidation with high dose Ara-C or with autologous or allogeneic bone marrow transplantation can expect a long-term disease free survival of 30 to 45%. Which mode of consolidation is preferable is still being investigated in randomized studies. Many disease characteristics have been put forward as prognostic variables in treatment outcome and as understanding of the biology of AML has continued to expand, cytogenetic and molecular markers have assumed greater importance in disease characterization, but the ultimate role that these play in prognosis remains incompletely defined. Once AML has relapsed, bone marrow transplantation may result in prolonged disease free survival as compared to use of salvage chemotherapy regimens. Because the long-term survival of all patients diagnosed with AML is only in the order of 10 to 20%, new treatment approaches to this disease are required. Current clinical and research efforts have focused on modulation of the immune system, modulation of drug resistance phenotypes, and understanding of the response of leukaemic cells to haematopoietic growth factors.

Acute Disease↗
PubMed1996

Expression and role in growth regulation of tumour necrosis factor receptors p55 and p75 in acute myeloblastic leukaemia cells.

Tumour necrosis factor (TNF)-alpha exerts multiple effects on human acute myeloblastic leukaemia (AML) cells in vitro, including (1) synergistic stimulation of proliferation with interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF); (2) inhibition of granulocyte-CSF (G-CSF) and stem cell factor (SCF)-induced growth; (3) suppression of multiplication of clonogenic leukaemic cells; (4) induction of autocrine growth. Recently, two distinct TNF receptors (TNF-Rs), TNF-Rp55 and TNF-Rp75, have been identified. In this study we show that both receptors are expressed on freshly isolated AML blasts, with p75 being the predominant TNF-receptor type. This study investigates the roles of these two receptors in TNF-alpha-driven growth regulation of AML blasts in vitro. Using a receptor-specific antibody, it is shown that both receptor types participate in TNF-alpha-mediated stimulation of GM-CSF/IL-3-induced proliferation and in TNF-alpha-induced autocrine growth. In contrast, the TNF-alpha-triggered growth inhibition (antiproliferation) and the potent suppression of G-CSF- and SCF-induced proliferation exclusively result from activation of TNF-Rp55. Taken together, these results suggest that the proliferative effects of TNF-alpha on AML blasts are mediated through both p55 and p75 TNF receptors, whereas the TNF-alpha-signalled growth inhibition is exclusively transduced via TNF-Rp55.

Adolescent↗
PubMed1996

Treatment of adult patients with acute lymphocytic leukemia in relapse.

Thirty-eight patients with a diagnosis of relapsed acute lymphocytic leukemia were accrued to a treatment program of reinduction therapy by the Eastern Cooperative Oncology Group (ECOG). A combination of mitoxantrone, etoposide (VP-16), and high-dose cytarabine (ARA-C) were administered over a five day period. Thirty-four patients were eligible for follow-up subsequent to treatment. Twenty-seven patients were in first relapse and seven were in second relapse. Fifteen of the thirty-four patients treated were given two cycles of induction chemotherapy. The complete remission (CR) rate for the entire group treated was 17%. The median duration of the CR was 2.4 months and the estimated median survival for first relapse patients was 4.5 months and 5.0 months for second relapse patient group. There were five deaths attributable to toxicity associated with the chemotherapy. The study emphasizes the difficulty in achieving durable remissions in adult patients with relapsed ALL.

Adolescent↗
PubMed1996

Use of growth factors during induction therapy for acute myeloid leukemia.

The use of colony-stimulating factors (CSFs) in acute myeloid leukemia (AML) remains controversial. Potential uses include shortening the period of neutropenia, inducing leukemic cells into the S-phase of the cell cycle, stem cell protection, inducing differentiation of leukemic cells, interrupting autocrine/paracrine loops, direct inhibition of leukemogenesis, and enhancing antimicrobial function. Data from the nine controlled studies of CSFs that have been reported between 1990 and 1995, with varying patient characteristics and other factors, indicate that growth factors have several uses in AML therapy. The published literature now suggests that the safety of CSFs is no longer a major clinical concern, and significant experience has been gained in reducing the period of neutropenia following induction therapy. Yeast-derived granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor appear to be effective and probably have an important role in the management of older adult patients with AML and for those patients with a significant risk for therapy-related morbidity and mortality. The use of CSFs as priming agents remains experimental; results of further prospective placebo-controlled studies, with laboratory correlates, are awaited.

Acute Disease↗