A stratification system for evaluating and selecting therapies in patients with relapsed or primary refractory acute myelogenous leukemia.
Explore the source record for details and available documents.
Acute Disease↗
Biomedical subjects
S Pierce
Publications and source records attributed to S Pierce.
Routine bone marrow exam during first remission of acute myeloid leukemia.
To detect relapse acute myeloid leukemia (AML) treatment protocols have called for bone marrow exams every 2 to 4 months in remission. To investigate the effect of replacing this policy with one calling for marrows only when blood count is abnormal (platelets < 100,000, neutrophils < 1,000, circulating blasts > 0%, unrelated to prior chemotherapy), we reviewed the records of all 444 patients with AML whose disease recurred ( > or = 5% marrow blasts unrelated to prior chemotherapy) for the first time between 1980 and 1995. The 375 patients with adequate follow-up were classified as (1) simultaneous--blood count abnormal when relapse noted without a normal marrow intervening between first abnormal count and relapse, 289 patients (77% of 375), (2) marrow first--blood count normal when relapse noted, 60 patients (16%), or (3) blood first--a normal marrow intervened between first abnormal blood count and relapse, 26 patients (7%). Interval between marrow exams and blood counts did not differ in the three groups (a 25-patient sample of the 289 patient simultaneous group was analyzed as representative of this group) with marrows done at a median of once monthly and blood counts at a median of once weekly from complete remission (CR) date to relapse date. The three groups also had similar first CR duration, and pretreatment cytogenetics. CR rates following salvage chemotherapy were 32% to 33% in the simultaneous and marrow first groups and 17% in the blood first group. We conclude that routine marrow exams for morphology are not needed in the great majority of AML patients in first CR.
Adolescent↗
A prospective study of conservative surgery alone in the treatment of selected patients with stage I breast cancer.
BACKGROUND: Randomized clinical trials have clearly demonstrated that the use of radiation therapy (RT) following breast-conserving surgery (CS) substantially reduces the risk of local recurrence. However, the low rate of local recurrence after CS and RT for patients without known risk factors, and the recent increase in the detection of smaller cancers due to mammographic screening have led to the speculation that a subgroup of patients who have a low risk of local recurrence without RT might be identified. In 1986, we initiated a one-arm, prospective clinical trial of CS alone for treatment of highly selected breast cancer patients without known risk factors for local recurrence. METHODS: The study had a sequential design with a planned accrual of 90 patients. Criteria for entry into the trial were: a unicentric, clinical TI infiltrating ductal, mucinous or tubular carcinoma without an extensive intraductal component or lymphatic vessel invasion; a wide excision with a pathologically-documented negative margin of at least 1 cm; and histologically negative axillary lymph nodes. No adjuvant RT or systemic therapy was administered. Seventy-six per cent of the lesions were detected by mammography alone. The median gross pathologic tumor size was 0.9 cm. The median patient age was 67 years. RESULTS: Eighty-seven patients were enrolled in the trial before it closed prematurely in 1992 because the predefined stopping boundary was crossed (i.e., the sixth local recurrence was observed). At that time, the average annual local recurrence rate was 4.2%. With a median follow-up of 56 months, there are now 14 patients (16%) with local recurrence as their site of first failure (average annual local recurrence rate: 3.6%). Four patients without local recurrence developed distant metastases. Three patients have died, one of metastatic breast cancer and two of unrelated causes. CONCLUSIONS: Even in a highly selected group of patients with early-stage breast cancer, there is a substantial risk of early local recurrence for those treated with wide excision alone.
Adenocarcinoma, Mucinous↗
Result of interferon-alpha therapy in patients with chronic myelogenous leukemia 60 years of age and older.
PURPOSE: To determine the response rate to interferon-alpha (IFN-alpha) in patients with chronic myelogenous leukemia (CML) aged 60 years and older. PATIENTS AND METHODS: Patients with CML aged 60 years and older included in all protocols with INF-alpha therapy for chronic phase CML at the M.D. Anderson Cancer Center were analyzed. They were treated with human leukocyte or recombinant human IFN-alpha 5x10(6) U/m2 daily alone or in combination with hydroxyurea or IFN gamma. The clinical characteristics of the patients were analyzed and their hematologic and cytogenetic responses to IFN-alpha and survival from the initiation of therapy were determined. Results were compared with those of younger patients treated in the same protocols. Treatment-related toxicity was also analyzed. RESULTS: Thirty-five of 274 (13%) patients included in trials of IFN-alpha-based regimens for CML were 60 years and older. Older patients had a higher percentage of bone marrow blasts (P = 0.04) and basophils (P = 0.09) than younger patients. Sixty-nine percent achieved a complete hematologic remission with IFN-alpha therapy, and 51% had a cytogenetic response, which was major in 26% and complete (Philadelphia chromosome-positive cells = 0%) in 20%, Their median survival was 64 months, and the estimated 5-year survival rate was 62%. These results were not different from those in younger patients. Twenty-two patients (63%) had at least grade 2 toxicity requiring dose adjustment. The most frequent side effects were neurotoxicity in 31% and chronic fatigue in 29%. CONCLUSIONS: Patients with CML 60 years of age and older respond well to IFN-alpha therapy, but experience more toxicity. This therapy should be considered for these patients if they are otherwise in good condition, with careful attention to IFN-alpha toxicity and its management.
Age Factors↗
Treatment of newly-diagnosed acute myelogenous leukaemia in patients aged 80 years and above.
In order to assess outcome following treatment of acute myeloid leukaemia (AML) in patients aged 80 years and above, we have studied 33 patients aged > or = 80 years treated between 1980 and 1994; 29 of these received treatment. The median age was 82 years (range 80-89). Three patients received daunorubicin ( > or = 60 mg/m2 daily x 3) alone or with low-dose ara-C, two patients received '3+7' with post treatment GM-CSF; 24 patients had higher doses of ara-C, generally with anthracyclines or fludarabine, and in nine cases with G or GM-CSF. The median survival of the treated patients was 3-4 weeks and only two were alive after 1 year (at 66 and 79 weeks). Complete remission (CR) occurred in 9/29 (31%). Only one of the nine remains alive in remission, at 76 weeks after the date of CR, whereas the other eight died in remission or had disease recurrence at a median of 11 weeks (range 5-37 weeks) after CR. The median survival of the four untreated patients was 10 weeks (range 3-38). Patients aged > or = 80 had, on average, worse outcomes than those observed in patients aged 70-79. Our results confirm that currently available chemotherapy is generally not indicated in patients aged 80 or over with AML.
Aged↗
Acute myeloid leukemia-type chemotherapy for myelodysplasia.
Explore the source record for details and available documents.
Acute Disease↗
Amsacrine and continuous-infusion high-dose cytosine arabinoside as induction therapy for patients with newly-diagnosed acute myelogenous leukemia.
The overall cure rate of adults with newly-diagnosed acute myelogenous leukemia (AML) treated with continuous infusion high-dose cytarabine (CIHDAC) is comparable to that with standard-dose ara-C plus anthracycline or amsacrine (AMSA). We tested whether the addition of AMSA to CIH-DAC improves the outcome of adults with untreated AML. 75 patients with untreated AML were treated with AMSA (75 mg/m2/day x 4) plus CIHDAC (1.5 g/m2/day x 4) for induction and, if in complete remission (CR), early and late intensification. Results were compared to those in 129 patients treated on a previous study with CIHDAC alone. The principal comparison in both groups was between those 117 patients (AMSA/CIHDAC n = 52, CIHDAC n = 65) who met the initial eligibility criteria for the AMSA/CIHDAC study (risk of early mortality < or = 1) and who were treated at a time when relatively few eligible patients were excluded (19% in the AMSA/CIHDAC group, 34% in the CIHDAC group). There was no difference between regimens in CR rate, remission duration, or survival in this cohort. When attention was turned to all 204 patients, outcome was superior with AMSA/CIHDAC very largely as a result of outcome in patients with APL. Aside from these patients, addition of amsacrine to CIHDAC did not appear to be productive.
Acute Disease↗
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↗
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↗
Acute lymphoblastic leukemia following preleukemic syndromes in adults.
Preleukemic syndromes (PLS) evolve to acute myeloid leukemia (AML) in 15-50% of cases, but rarely transform to acute lymphoblastic leukemia (ALL). AML following preleukemic syndromes has a poor prognosis, but little is reported about the outcome of secondary ALL. From the adult leukemia database at MD Anderson Cancer Center, nine patients with ALL following myelodysplastic syndrome (MDS) (n=6), smoldering leukemia (n=1), or cytopenias with dysplastic features (n=2) were identified. Clinical and laboratory features were abstracted from the database, patient charts, review of the bone marrows and special laboratory studies. The median interval from diagnosis of PLS to ALL was 6 months. Blasts with lymphoid morphology and terminal deoxynucleotidyltransferase (TdT) and periodic acid Schiff (PAS) staining were present in eight of nine cases and four of six cases respectively. T cell and myeloid markers were expressed in the majority of cases, but T cell gene rearrangements were not detected. Only one patient had electron microscopic myeloperoxidase-positive staining. Two patients later transformed to AML. Patients were predominantly male (89%) with a median age of 69 years. The complete remission (CR) rate with ALL-directed chemotherapy (78%) was comparable to that of other adult ALL patients (74%) (n=327) without excess myelosuppression. Marrow dysplasia persisted in CR in three of seven cases. The median remission duration of 16 months (range 4.5 to 51+ months) and the median overall survival of 21 months (range 1 to 55+ months) were comparable to that of ALL patients overall. ALL following preleukemic syndromes is a distinct syndrome with T cell and myeloid markers and responds well to ALL-directed therapy. The presence of myeloid and lymphoid markers suggests the transformation of an early stem cell.
Adult↗
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↗
The value of high-dose systemic chemotherapy and intrathecal therapy for central nervous system prophylaxis in different risk groups of adult acute lymphoblastic leukemia.
Although central nervous system (CNS) leukemic relapse is frequent in adult acute lymphocytic leukemia (ALL), the need for prophylaxis in different risk groups for CNS relapse, the value of high-dose systemic and intrathecal (IT) chemotherapy, and the timing of prophylaxis are not well defined. This analysis was conducted to investigate these questions and to assess the value of a risk-oriented CNS prophylaxis approach. We analyzed the incidence of CNS leukemia after initiation of therapy in patients treated on 4 consecutive trials for adult ALL including different CNS prophylactic modalities. The treatment groups included (1) the program preceeding the vincristine-Adriamycin-dexamethasone (VAD) regimen, with no CNS prophylaxis; (2) the VAD regimen with prophylaxis using high-dose systemic chemotherapy; (3) the modified VAD program with high-dose systemic chemotherapy to all patients and IT chemotherapy for high-risk patients after achieving complete remission; and (4) the hyperCVAD program with early high-dose systemic and IT chemotherapy starting during induction to all patients, with more IT injections (16IT) administered to the high-risk group for CNS relapse compared with the low-risk group (4IT). A total of 391 patients were included, 73 of whom were treated with preVAD, 112 with VAD, 114 with modified VAD, and 92 with hyperCVAD. The overall CNS relapse rates were 31%, 18%, 17%, and 3%, respectively for the 4 groups (P < .001). For the high-risk group for CNS relapse, they were 42%, 26%, 20%, and 2%, respectively (P < .001). The differences in CNS relapse rates in the low-risk group were not statistically significant. At 3 years, the overall CNS leukemia event-free rates were 48%, 76%, and 98%, respectively (P < .001). In the high-risk group, the CNS event-free rates were 38%, 66%, 75%, and 98%, respectively (P < .001); however, there was no difference in the low-risk group. We conclude that (1) high-dose systemic chemotherapy is a useful prophylactic measure; (2) early IT chemotherapy is necessary to reduce the incidence of CNS leukemia overall and in the high-risk group; and (3) a risk-oriented approach is appropriate to tailor the intensity of CNS prophylaxis.
Adolescent↗
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↗
The purported link between agent orange and cancer.
Explore the source record for details and available documents.
2,4,5-Trichlorophenoxyacetic Acid↗
Managing cancer pain: content and scope of an educational program for nurses who work in predominantly rural areas.
A great deal of effort is being expended at national, state and local levels to improve cancer pain management in the United States. The fact that cancer patients continue to experience "unrelieved pain" is of concern to professional caregivers and families, as well as to the patients themselves. This article describes the content and scope of an educational program for nurses who work in predominantly rural areas. Content of the program and the evaluation process are described in detail in order to provide other caregivers with a model that could be implemented in similar settings.
Chronic Disease↗
Immune-mediated and unusual complications during interferon alfa therapy in chronic myelogenous leukemia.
PURPOSE: Long-term treatment with interferon alfa (IFN alpha) can produce or exacerbate immune-mediated complications (IMC). The purpose of this study was to analyze the experience with IMC and unusual complications in patients with chronic myelogenous leukemia (CML) undergoing IFN alpha treatment. PATIENTS AND METHODS: The occurrence of IMC and unusual complications was evaluated in patients with Philadelphia chromosome (Ph)-positive CML. RESULTS: Well-documented and clinically evident complications developed in 35 patients after a median of 14 months of IFN alpha treatment. These included 28 (5%) of 581 patients with Ph-positive CML treated with IFN alpha-containing regimens at M.D. Anderson Cancer Center (MDACC) and seven patients referred for opinion or problems who were on other studies. Hypothyroidism occurred in 11 patients (2%), immune-mediated hemolysis in seven (1%), and connective tissue diseases in 11 (2%). Other unusual occurrences included congestive heart failure (CHF; n = 4), porphyria cutanea tarda (PCT; n = 3), membranous glomerulonephritis (MGN; n = 1), and vitiligo (n = 1). IFN treatment was discontinued in 19 patients and the dose was reduced in five. Ten of 11 patients (91%) with immune-mediated hypothyroidism and eight of 11 (73%) with connective tissue diseases had some degree of cytogenetic response at the time of the event. CONCLUSION: Although the frequency of IMC is low, patients treated with IFN alpha should be monitored for signs and symptoms of autoimmunity.
Adolescent↗
Cytogenetic and clinical correlates in AML patients with abnormalities of chromosome 16.
Abnormalities of chromosome 16 in AML include del(16q), inv(16) and t(16;16). These three groups have been categorized together and have been associated with high complete remission (CR) and survival rates following Ara-C-based chemotherapy. We have reviewed the 63 AML or MDS patients with an abnormality of chromosome 16 treated at MD Anderson Cancer Center (MDACC) over the past 18 years. Marked differences in survival and remission duration (RD) were noted between the inv(16) or t(16;16) patients and those with del(16q), whose outcome was no better than other M4 AML or MDS patients treated during the same period. Other differences characterizing del(16q) included a lack of CNS relapses, lower incidences of eosinophilia and M4 FAB subtype. Half the inv(16) patients had additional karyotypic abnormalities. The overall survival and remission duration for those patients were no different from those for patients with inv(16) alone, although the probability of remaining in first CR at 2 years was higher in the inv(16) alone group. There was no difference in overall survival for the 45 patients who received HDAC vs those who did not. The incidence of CNS relapse was, however, markedly reduced for the HDAC patients. Eosinophilia did not correlate with improved survival. We conclude that del(16q) confers a different prognosis from inv(16) and t(16;16) and for the purposes of prognostication or treatment recommendations should no longer be categorized with them. Additional karyotypic changes however, which accompany inv(16) in 50% of cases do not influence the overall outcome compared to patients with inv(16) alone.
Acute Disease↗
Change in karyotype between diagnosis and first relapse in acute myelogenous leukemia.
We compared karyotype at first relapse with presenting karyotype in 212 patients with AML seen at MD Anderson Cancer Center (Houston, TX, USA) between 1975 and 1994. In 38% the karyotypes at diagnosis and relapse were identical. A stable karyotype was most frequent (70%) among patients who presented without cytogenetic abnormalities, suggesting that the finding of a normal karyotype is usually not due to sampling error. In contrast, a finding of insufficient metaphases at diagnosis was repeated at relapse in only 6% of cases. A change in karyotype occurred in 67% of 101 patients who presented with an abnormal karyotype and had sufficient metaphases for evaluation at relapse. The great majority of changes involved clonal evolution, clonal devolution (regression), or both; a purely normal karyotype and unrelated clones were seen in 11 and three of the 101, respectively. Change in karyotype between diagnosis and relapse and type of change were unrelated to remission duration. The only group in which karyotype at relapse vs that at diagnosis had a possible bearing on achievement of second CR were patients who presented with abnormalities other than inv(16), t(8;21) or t(15;17) and who at relapse had only normal metaphases; such patients had higher CR rates than comparable patients who retained their presenting abnormalities.
Chromosome Aberrations↗