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Biomedical subjects

S O'Brien

Publications and source records attributed to S O'Brien.

At least 199 records · Page 11Linked to original sources
PubMed1996

Secondary acute promyelocytic leukemia. Characteristics and prognosis of 14 patients from a single institution.

The aims of this study were to analyze the characteristics and outcome of patients with secondary acute promyelocytic leukemia (APL) and compare them to those with primary APL. One hundred and thirteen patients referred to our service with a diagnosis of APL were reviewed. Fourteen were classified as secondary APL. Nine were induced with chemotherapy, and five with all-trans retinoic acid plus chemotherapy. Pretreatment characteristics, response to therapy and outcome of primary vs secondary APL were compared by standard statistical methods. Secondary APL constituted 12% of all APL cases. Patients with secondary APL were significantly older (median age 56 vs 36 years; P < 0.01) and had a lower incidence of hypofibrinogenemia (P < 0.01) than those with primary APL. The complete response (CR) rates were similar with secondary vs primary APL (CR rates 79 vs 69%), as were CR duration and survival. The CR rates at 5 years were 57 and 45%, respectively(P not significant), and the survival rates 37 and 35%, respectively (P not significant). The incidence of secondary APL within APL disease (12%) was similar to the incidence of secondary acute myeloid leukemia (AML) in karyotypes not known to be therapy-related (diploid, t(8;21), inversion 16: incidences 9 to 12%), but was significantly lower than in karyotypes known to be therapy-related (chromosome 5 or 7 abnormalities, 11q; incidences 30 and 33%). We conclude that secondary APL has general characteristics and outcome similar to primary APL. it is more likely a second primary rather than therapy-related AML, and should be treated in a manner similar to primary APL.

Adult↗
PubMed1996

Causes of initial remission induction failure in patients with acute myeloid leukemia and myelodysplastic syndromes.

We analyzed 144 of 475 previously untreated patients with acute myeloid leukemia (AML, n = 87) and 'high-risk' myelodysplastic syndromes (MDS, n = 57) who failed to achieve a complete remission with fludarabine- and high-dose cytarabine-containing regimens between 1991 and 1994. The AML and MDS groups were comparable with regard to age, major prognostic indicators, supportive care received, type of antileukemia response and causes of death and were considered together. The causes of death of 118 evaluable patients were compared to a series of 123 AML initial remission induction failures previously reported from our institution. The induction failure rate was significantly lower (30 vs 43% P <0.001). We found a significant decrease in fatal infections (autopsied patients, P = 0.001) and a reduction in bacterial (autopsied and non-autopsied patients, P <0.005) but not fungal (non-autopsied patients, P = 0.93; autopsied patients P = 0.15) infections as causes of induction death. Pulmonary hemorrhage was twice as common in the present report (P < 0.005, with pulmonary hemorrhage almost three times as common as fatal cerebral hemorrhage. A comparison restricted to the AML patients in the present study yielded similar results. We conclude that the mortality profile in AML remission induction has undergone substantial changes at our institution since our last report, probably as a consequence of the introduction of new chemotherapy regimens and supportive care modalities.

Acute Disease↗
PubMed1996

Engraftment of chronic prolymphocytic and T cell leukemia in SCID mice.

Engraftment of human acute leukemia cells in immunocompromised (SCID) mice has resulted in in vivo models for exploration of human tumor biology. Attempts at engraftment of chronic leukemia cells have been generally unsuccessful. We have engrafted cells from three human chronic leukemias in SCID mice. Cell populations were from two patients with chronic lymphocytic leukemia (CLL) and either increased proolymphocytes (CLL-Pro; patient 1), or prolymphocytic transformation (PLL; patient 2) and from a third patient with newly diagnosed T cell CLL. Both fresh and cryopreserved cells were used and were injected intravenously, intraperitoneally, or both, after conditioning with cyclophosphamide. In addition, cells derived from a mouse spleen engrafted with human leukemia were passaged into another mouse. The animals were observed daily for signs of disease or appearance of tumors and sacrificed when terminally ill. At intervals blood samples were obtained and analyzed for the presence of human cells or DNA. Human leukemic cells were demonstrated by polymerase chain reaction (PCR) analysis of the human DQalpha gene or positive staining for human leukocyte common antigen (LCA). The presence of Epstein-Barr virus (EBV)-positive cells was also investigated by PCR analysis. Disseminated tumors developed in most mice inoculated with cells from the first patient, and this was associated with shortened survival times. The methods of administration, use of fresh or frozen samples, or the size of the inoculum had no effect on the development of leukemia. Survival of the mouse receiving passaged cells was similar to mice inoculated with fresh cells. Extensive histologic, immunophenotypic, and DNA studies were performed on organs from mice engrafting with cells from patient 1. PCR analysis for EBV sequences was negative in the mice engrafting from all three cases. The successful engraftment of human CLL-Pro PLL and T cell CLL in SCID mice, and the reproducibility of this effect using frozen cells, will provide a model for exploration of disease biology and for investigations of new drugs or combinations that may be useful in the treatment of CLL.

Aged↗
PubMed1996

Evaluation of CI-973, a platinum analogue, in refractory or relapsed acute leukemia.

The purpose of the study was to define the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of CI-973 a new platinum analogue, in patients with refractory or relapsed acute leukemia. CI-973 was given as a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or relapsed acute leukemia, at doses ranging from 150 mg/m2 to 1350 mg/m2 per course. Thirty-six patients were treated including 18 patients with acute myelogenous leukemia (AML), four with acute lymphocytic leukemia (ALL) and 14 with chronic myelogenous leukemia in blastic phase (CML-BP). Severe gastrointestinal and renal side-effects were the dose-limiting toxicities occurring in four of five patients treated with CI-973 1200 to 1350 mg/m2 per course. At the MTD of 1000 mg/m2 per course, three of 13 patients treated (23%) had moderate to severe nausea and vomiting, three (23%) had moderate diarrhea and one had moderate mucositis. Among 21 patients treated at > or = 1000 mg/m2 (15 AML, 6 CML-BP) no objective complete or partial responses were observed. Twelve of 18 patients (66%) with evaluable marrows on day 14 showed significant suppression of marrow blasts percentage and marrow leukemic infiltrate percentage. Tests for measurement of DNA adduct formation in leukemic cells in vivo after CI-973 therapy, and in vitro following exposure of leukemic cells to CI-973 were developed. This study defined the MTD of CI-973 to be 1000 mg/m2 by continuous infusion over 5 days every 3 to 4 weeks in patients with refractory or relapsed acute leukemia. Gastrointestinal and renal side-effects were dose-limiting. No objective responses were noted in this heavily resistant population. Correlations between CI-973-induced DNA adduct formation and individual patient response to CI-973 will help to define its role in leukemia subsets.

Acute Disease↗
PubMed1996

Factors predicting complete remission and subsequent disease-free survival after a second course of induction therapy in patients with acute myelogenous leukemia resistant to the first.

Patients with newly diagnosed acute myelogenous leukemia (AML) with persistent leukemia after their first course (CO1) of induction chemotherapy are generally given a second similar course, although their outcome is known to be worse than CO1 responders even when a complete remission (CR) is achieved. To identify specific patients who should or should not receive a second induction course identical to the first we analyzed outcome in 370 patients with persistent AML after CO1 who received a second identical course. One hundred and forty-two (38%) achieved CR on this course; median subsequent disease-free survival (DFS) in these 142 was 29 weeks and 10% were alive in CR at 5 years. The 5-year DFS of CO2 responders was significantly lower than that of CO1 responders (10 vs 24%, P < 0.001). Logistic regression identified pretreatment cytogenetic abnormalities (except inv 16, t(8;21), or t(15;17)), presence of an antecedent hematologic disorder or secondary AML as each having unfavorable prognostic import similar to the case in untreated patients. Treatment with "high-dose' rather than standard-dose cytarabine increased the probability of 2nd course CR. The occurrence of pneumonia, sepsis, or major hemorrhage were prognostically unfavorable, primarily in the high-dose cytarabine group, and, once in CR, DFS was shorter in this group. Equations predicting probability of 2nd course CR were derived. If validated prospectively these could be used to assign patients to either receive a second course of initial induction therapy or to change to salvage or investigational therapy after the first course. Alternatively, they could be used to stratify patients entering a prospective randomized trial comparing these two strategies.

Adult↗
PubMed1996

The knowledge and attitudes of experience oncology nurses regarding the management of cancer-related pain.

PURPOSE/OBJECTIVES: To describe the knowledge and attitudes of North Carolina nurses toward the management of cancer-related pain. The analysis focused on knowledge, attitude, and perception of barriers to pain management. DESIGN: Exploratory, descriptive. SETTING: North Carolina. SAMPLE: A survey of 1,400 RNs were stratified by educational background and Area Health Education Center regions of the state; the response rate was 24%. METHODS: An adapted version of The Wisconsin Pain Initiative Survey mailed to participants. MAIN RESEARCH VARIABLES: Nurses' knowledge, attitudes, and perception of perceived barriers to managing cancer-related pain. FINDINGS: Nurses who have cared for patients with cancer are more knowledgeable and have more liberal attitudes toward pain management from nurses who have not cared for patients with cancer. North Carolina nurses report knowledge and perception of barriers to pain management similar to those of Wisconsin nurses. CONCLUSIONS: The experience of caring for patients who have cancer and pain influences nurses to report more liberal attitudes toward pain management. IMPLICATIONS FOR NURSING PRACTICE: Although nurses report increased knowledge of pain management in general, deficits continue to exist. Further research is needed to more fully understand the effect of educational and experience on practice.

Adult↗
PubMed1996

Clinical and laboratory studies of 2-chlorodeoxyadenosine +/- cytosine arabinoside for relapsed or refractory acute myelogenous leukemia in adults.

Previous studies in pediatric patients with acute myelogenous leukemia (AML) have suggested that 2-chlorodeoxyadenosine (2CdA) is an effective therapeutic agent. Santana et al (J Clin Oncol 1992; 10: 364-370) reported a CR rate of 8/17 (95% Cl 23-72%) in children with relapsed AML and a median first CR of 21 months. The activity of 2CdA in adults with relapsed or refractory leukemia was therefore investigated in a phase I study. In the phase II study, based on biochemical modulation rationale, 2CdA was combined with Ara-C for adults with relapsed AML to test the effectiveness of this combination therapy. In the phase I study 27 patients (25 AML and two MDS) with a median first CR duration of 21 weeks, received 2CdA at doses ranging from 5 to 13 mg/m2/day by continuous infusion (CI) for 7 days. In vitro and ex vivo pharmacologic studies performed to determine the effect of pretreatment with 2CdA on Ara-CTP accumulation in leukemic blasts demonstrated a 50-65% increase in the rate of Ara-CTP accumulation. Based on this biochemical modulation, 2CdA (12 mg/m2/day x 5 days by CI) was combined with Ara-C (1 g/m2/day over 2 h) in a phase II study. Seventeen patients (15 AML, two MDS) with relapsed AML (median 1st CR of 19 weeks) were treated. In the phase I study two patients died before the day 14 marrow (ED). Marrow hypoplasia developed in 16 of the remaining 25. Leukemic regrowth occurred in nine after a median hypoplastic period of 2 weeks (range 1-3 weeks). The other seven patients died with aplastic marrows, median duration of hypoplasia was 2 weeks, range 1-4 weeks. None achieved CR and the median survival was 10.5 weeks. Toxicity generally was mild except for three late occurring cases of grade III or IV renal dysfunction and two cases of tumor lysis syndrome. The MTD was 10.8 mg/m2/day x 7 days. In the phase II study two patients, both with AML, achieved CR (95% CI 1-33%). In both cases leukemia relapsed after 10 weeks and 17 weeks. There was one ED. Most (11/16) cleared their marrow although leukemic infiltrate regrew in six cases. Toxicity was generally mild, with two episodes of grade 2 GI bleeding, one episode of severe renal dysfunction and one case of grade 2 CNS toxicity. We conclude that as a single agent 2CdA at the MTD is a cytoreductive agent but is not sufficient to achieve CR in adults with relapsed AML. While combination of Ara-C with 2CdA increases the Ara-CTP uptake in these heavily treated patients this regimen does not appear to be an improvement over existing modalities.

Adult↗
PubMed1996

Pneumonia during remission induction chemotherapy in patients with AML or MDS.

We analyzed the 67 of 278 patients with newly-diagnosed AML or 'high-risk' MDS, treated in 1994 and 1995, who developed pneumonia during course 1 of their induction therapy. Pneumonia responded to treatment in 66%, but outcome depended on when pneumonia was diagnosed. Patients with pneumonia diagnosed during week 1 or 2 (group 2 patients) had the lowest response rate (43%). Patients who developed pneumonia in the 3rd week after treatment initiation had the best outcome with all 16 patients recovering. Patients presenting with pneumonia had an intermediate response rate (75%). The different patient groups were comparable with regard to age, underlying disease, prophylactic therapy, and G-CSF application. Although a lower CR rate was not entirely responsible for the lower response rate in group 2, failure to achieve CR predicted unsuccessful treatment of pneumonia in all groups. Fungal pathogens appeared more common in group 2 patients. However, in these patients, administration of amphotericin B was associated with a significantly higher failure rate (15/21 failures vs 2/9 who received no amphotericin B). We conclude that patients who develop pneumonia during week 1 or 2 are a high-risk group, and that use of amphotericin B indicates a particularly poor prognosis, although we present data suggesting that earlier use of amphotericin might be beneficial. Furthermore, since achievement of CR was an important prognostic factor in all groups, WBC transfusions particularly from donors given G-CSF should be considered as a therapeutic option. Finally, since time to failure of induction therapy and time to CR were similar in high-risk patients, new chemotherapy regimens could potentially improve both the CR rate and the outcome of pneumonia.

Acute Disease↗
PubMed1996

Clinical experience with fludarabine in hemato-oncology.

Fludarabine monophosphate (Fludara) is a purine analogue which entered clinical trials in 1982. Although inactive in solid tumors, Fludara has marked activity in indolent lymphoproliferative disorders. The exact mechanism of action of Fludara is uncertain. Fludara has been established as the most active single agent in chronic lymphocytic leukemia (CLL) in single arm and comparative clinical trials. The activity has been demonstrated in both previously treated and initially treated patients. Marked activity has been noted in patients with low grade lymphoma, in particular, those with a follicular morphology and in Waldenstrom's macroglobulinemia. Combinations of fludarabine with alkylating agents, anthracyclines, and anthraquinones have led to clinically useful combination approaches. The ability of fludarabine to modulate the levels of the triphosphate form of cytosine arabinoside (ara-C) in acute leukemia cells has led to the development of combinations of fludarabine and ara-C. These combinations have demonstrated marked activity in treatment of relapsed and previously untreated patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The ability to modulate the activity of pyrimidines and to inhibit repair of DNA damage caused by alkylating agents, anthracyclines, and other DNA active drugs suggest that the future of fludarabine will be in combination approaches to modulate the activity of other agents. These activities may extend its role to use in solid tumors.

Antineoplastic Agents↗
PubMed1995

Growth and biologic properties of karyotypically defined subcategories of adult acute lymphocytic leukemia in mice with severe combined immunodeficiency.

Modest progress has been achieved over the past two decades in the treatment of adult acute lymphocytic leukemia (ALL). With modern therapy, response rates are 70% to 80%, but cure rates only average 25% to 30%. Improved in vivo models are needed to investigate the biology of adult ALL and to test new treatment concepts. Fresh leukemia samples from children with ALL have been successfully transplanted into mice with severe combined immunodeficiency (SCID), but no experience exists for adult ALL. We treated SCID mice with 2 mg cyclophosphamide 24 hours before intravenously injecting 20 x 10(6) viable leukemia cells obtained from 13 patients with newly diagnosed adult ALL within five defined phenotype/karyotype subcategories. Ten (76%) of 13 injected leukemia specimens representing all five categories engrafted. The median survival duration of mice was 20 weeks from the time of leukemia cell injection. The rate of engraftment by ALL subset was as follows: two of two T-cell, two of three t(11q23), two of two hyperdiploid, two of three t(9;22), and two of three diploid ALL. The pattern of organ involvement by leukemia in the mice was similar to that of the human disease. Immunohistochemistry and flow cytometry documented the stability of each leukemic phenotype after passage through SCID mice. Cells transplanted from the spleen and bone marrow of mice engrafted with ALL into recipient mice resulted in consistent engraftment. The survival duration in passage groups was similar to that in groups injected with primary cells. The high frequency of engraftment, availability of frozen original specimens, and successful passages in SCID mice provide an in vivo model of adult ALL suitable for further studies of the disease biology and for design of drug studies for the different subtypes of previously untreated adult ALL.

Adolescent↗
PubMed1995

Homoharringtonine therapy induces responses in patients with chronic myelogenous leukemia in late chronic phase.

Homoharringtonine (HHT) is a plant alkaloid with potent myelosuppressive activity and little toxicity when used in a continuous infusion schedule. The antileukemic efficacy of HHT has been shown in acute myeloid leukemia, but has not been investigated in chronic myelogenous leukemia (CML). Seventy-one patients with Philadelphia chromosome-positive (Ph+) CML in late chronic phase (time from diagnosis to therapy longer than 12 months) were treated with a continuous infusion of HHT at a daily dose of 2.5 mg/m2 for 14 days for remission induction and for 7 days every month for maintenance. The median number of courses given was 6 (range, 1 to 35) and 21 patients (30%) continue on treatment. Forty-two of 58 patients (72%) evaluable for hematologic response achieved a complete hematologic remission, and 9 (16%) had a partial hematologic remission. Twenty-two of 71 patients (31%) developed a cytogenetic response; it was major (Ph+ cells less than 35%) in 11 (15%) and complete (Ph+ cells 0%) in 5 (7%). Significant myelosuppression occurred in 39% of induction courses and 9% of maintenance courses. Fever or documented infection was present in 26% of induction courses and in only 8% of maintenance courses. Nonmyelosuppressive toxicity was minimal. Homoharringtonine produced hematologic remissions in the majority of patients with advanced chronic-phase CML. Cytogenetic response occurred in some patients without an association with myelosuppression, and these responses may be prolonged. Future studies investigating homoharringtonine in combination with other active agents in CML, such as interferon, are warranted.

Adult↗
PubMed1995

The breakpoint cluster region site in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. Clinical, laboratory, and prognostic correlations.

BACKGROUND: The breakpoint site of the breakpoint cluster region (bcr) has been correlated with patient characteristics, with the disease phase, and with the prognosis of patients with chronic myelogenous leukemia (CML), but the findings remain controversial. METHODS: Appropriate restriction enzymes and the 3' and universal probes were used to map the breakpoint site by Southern blot analysis into 5' and 3' breakpoints and a breakpoint in zone 3 (or fragment 2) in 362 patients in different phases of CML (238 in early chronic phase, 69 in late chronic phase, 31 in accelerated phase, and 24 in blastic phase). Standard statistical methods were used to evaluate differences in characteristics and in prognosis by the breakpoint site. RESULTS: No correlation was noted between CML phases and breakpoint site. Among patients in the early chronic phase, thrombocytosis was significantly associated with the 3' breakpoint site (P = 0.02), whereas peripheral basophilia occurred more frequently with the 5' breakpoint site (P = 0.05). Other patient and disease characteristics were similar in frequency among the breakpoint-site subgroups. There was no difference in response to alpha-interferon therapy (186 patients treated) by the breakpoint site. Survival, dated from either referral to the authors' institution or from diagnosis, was not significantly different among patients with early chronic phase CML by the breakpoint site. However, patients with a 3' deletion tended to have a shorter survival. CONCLUSION: Determination of the breakpoint site by Southern blot analysis does not help to predict prognosis of patients with CML.

Chromosomes, Human, Pair 22↗
PubMed1995

Interferon maintenance therapy for patients with chronic lymphocytic leukemia in remission after fludarabine therapy.

Many patients with chronic lymphocytic leukemia (CLL) achieve remission after treatment with fludarabine chemotherapy. Most of these patients, however, later experience relapse. In addition, immunologic deficits may persist even in patients in complete remission; lymphopenia, predominantly involving the CD4 population, is universal after fludarabine therapy. We used recombinant alpha interferon (IFN-alpha) maintenance therapy in patients with CLL who achieved remission in response to fludarabine therapy to determine its effect on residual disease, assessed by either bone marrow biopsy or flow cytometry, and on immune restoration. Thirty-one patients were treated with IFN-alpha (3 x 10(6) U by subcutaneous injection three times weekly). Twenty-two patients (71%) were in complete remission (CR) and nine (29%) were in partial remission (PR). Of the 22 patients in CR, 21 (95%) had evidence of residual disease at the start of IFN-alpha therapy. Low CD4 levels were noted in 93% of patients, low IgG levels in 45%, and anergy or hypoergy in 52%. Only one patient in PR achieved a CR on IFN-alpha therapy: the only patient who had had no prior fludarabine but had been treated with chlorambucil and prednisone. All patients in CR with minimal residual disease had persistent disease after IFN-alpha treatment. There were no increases in CD4 counts or IgG levels; three patients with borderline responses to skin testing had an increase in the number of positive tests while on IFN-alpha. The time to progression was no different in patients treated with IFN-alpha than in a historical control group of patients who had received no further therapy after fludarabine. In summary, the use of IFN-alpha maintenance did not eradicate residual disease, restore immune function, or prolong remissions in patients with CLL responsive to fludarabine.

Adult↗
PubMed1995

Relapse of acute myelogenous leukemia during low dose interleukin-2 (IL-2) therapy. Phenotypic evolution associated with strong expression of the IL-2 receptor alpha chain.

BACKGROUND: Interleukin-2 (IL-2) has produced remissions in patients with solid tumors, predominantly malignant melanoma and renal cell carcinoma. Recently, clinical trials have assessed the therapeutic benefit of this cytokine in acute myelogenous leukemia (AML). However, little is known about the potential of IL-2 to promote the growth of leukemic cells in vivo. METHODS: A patient with acute myelocytic leukemia whose leukemic blasts displayed lymphoid (TdT+ and CD4+) and myeloid features (myeloperoxidase [MPO]+ and CD13+) is reported. The IL-2 receptor alpha chain (CD25 antigen) was present on 28.9% of his blasts. After entering complete remission with chemotherapy, he was treated on a protocol using IL-2 maintenance. RESULTS: Six weeks after beginning low-dose IL-2, his leukocyte count increased to 448,000/microliters with 86% blasts. The phenotype of these blasts was different from that at diagnosis with expression of the CD25 antigen and the CD33 antigen on 75.9% and 74.8 of the blasts, respectively. Furthermore, 30% of the cells were TdT+, whereas MPO was not detectable. CONCLUSION: The rapid course of relapse, phenotypic evolution, and the high expression of CD25 antigen on the blasts after IL-2 therapy raise the possibility that the cytokine therapy may have promoted the growth of leukemic cells.

Humans↗
PubMed1995

Topotecan in chronic lymphocytic leukemia.

BACKGROUND: Topotecan is one of a new class of agents that targets topoisomerase I (Topo I) and stabilizes the DNA-topo1 complex, ultimately resulting in cell death. The rationale for the use of topotecan in chronic lymphocytic leukemia (CLL) is based on the finding that levels of Topo I are elevated in the lymphocytes of patients with this disease. METHODS: Twelve patients with CLL were treated with topotecan to assess its clinical efficacy; in addition, DNA-protein cross-linking was measured after exposure of the cells to topotecan, in an attempt to correlate potential anti-CLL effects with this parameter. The median age of the patients was 63 years; all had received prior therapy with fludarabine and four (33%) were resistant to fludarabine. Four patients (33%) had also received therapy with chlorambucil, and three of them were resistant to this agent. Seven patients (58%) were Rai stage I-II and five (42%) were Rai stage III-IV. Topotecan was given as a 30-minute infusion at a daily dose of 2 mg/m2 for 5 days, and courses were repeated monthly. Cells were obtained from the patients before treatment and exposed to 2 microM topotecan or control in vitro. In addition, cells were obtained from patients after they received the first dose of topotecan and protein-bound DNA was measured with the same technique. RESULTS: No patient responded to therapy with topotecan (95% confidence interval, 0-27%). Nonhematologic toxicity was mild and thrombocytopenia occurred in four of eight patients whose conditions could be evaluated. One patients died of myocardial infarction and another died of fungal pneumonia. DNA-protein cross-linking was detected in all nine patients whose cells were assessed in vitro, with levels of cleavable complex ranging from twofold to 7.5-fold that of the control cells. Only two of eight patients with evaluable conditions had increased cross-linking detectable in circulating cells after the first dose of topotecan, which was consistent with the drug's lack of effect in vivo. CONCLUSIONS: Although exposure of cells from patients with CLL to topotecan in vitro at 2 microM resulted in detectable protein-DNA cross-linking, this effect was not seen in patients who received a bolus dose of 2 mg/m2, and no remissions were noted in 12 patients.

Adult↗
PubMed1995

Prolonged survival in chronic myelogenous leukemia after cytogenetic response to interferon-alpha therapy. The Leukemia Service.

OBJECTIVE: To determine whether a cytogenetic response after interferon-alpha therapy in patients with chronic myelogenous leukemia is independently associated with improved survival. DESIGN: Retrospective analysis. PATIENTS: 274 patients with a diagnosis of Philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase who were treated with interferon-alpha-based programs between 1982 and 1990. INTERVENTION: Therapy with daily subcutaneous interferon-alpha given at 5 x 10(6) U/m2 body surface area (highest dose schedule allowed on studies) or the maximally tolerated lower-dose schedule. RESULTS: Overall, 219 (80%) patients achieved a complete hematologic response and 104 (38%) achieved a major cytogenetic response (< 35% Philadelphia chromosome-positive cells). Estimated median survival was 89 months. Several pretreatment factors were associated with failure to achieve a major cytogenetic response and with worse survival. The existing prognostic models were generally predictive of which patients were likely to achieve a major cytogenetic response (P < or = 0.01) and of survival outcomes (P < or = 0.01). Multivariate analysis identified bone marrow basophilia (P < 0.01) and splenomegaly (P < 0.01) as independent poor prognostic factors for survival. Achievement of a major cytogenetic response, entered as a time-dependent variable while accounting for the other independent factors, was associated with improved survival (P < 0.001). Comparison of survival (dated from 12 months into therapy) with cytogenetic response at 12 months showed that a cytogenetic response was associated with longer survival (P < 0.001). CONCLUSION: Achieving a cytogenetic response with interferon-alpha therapy in patients with chronic myelogenous leukemia was independently associated with improved survival when tested as a time-dependent variable in a multivariate analysis, and this association was confirmed by landmark analysis at 12 months.

Adolescent↗