A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission.
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Intensive, myelosuppressive therapy is necessary to maximize outcomes for patients with acute myeloid leukemia (AML). A comparison was made of 3 aggressive postremission approaches for children and adolescents with AML in a randomized trial, CCG-2891. A total of 652 children and adolescents with AML who achieved remission on 2 induction regimens using identical drugs and doses (standard and intensive timing) were eligible for allocation to allogeneic bone marrow transplantation (BMT) based on matched related donor status (n = 181) or randomization to autologous BMT (n = 177) or to aggressive high-dose cytarabine-based chemotherapy (n = 179). Only 115 patients (18%) refused to participate in the postremission phase of this study. Overall compliance with the 3 allocated regimens was 90%. At 8 years actuarial, 54% +/- 4% (95% confidence interval) of all remission patients remain alive. Survival by assigned regimen ("intent to treat") is as follows: allogeneic BMT, 60% +/- 9%; autologous BMT, 48% +/- 8%; and chemotherapy, 53% +/- 8%. Survival in the allogeneic BMT group is significantly superior to autologous BMT (P =.002) and chemotherapy (P =.05); differences between chemotherapy and autologous BMT are not significant (P =.21). No potential confounding factors affected results. Patients receiving intensive-timing induction therapy had superior long-term survival irrespective of postremission regimen received (allogeneic BMT, 70% +/- 9%; autologous BMT, 54% +/- 9%; chemotherapy, 57% +/- 10%). Allogeneic BMT remains the treatment of choice for children and adolescents with AML in remission, when a matched related donor is available. For all others, there is no advantage to autologous BMT; hence, aggressive nonablative chemotherapy should be used. (+info)
Interleukin-6 and interleukin-10 levels in chronic lymphocytic leukemia: correlation with phenotypic characteristics and outcome.
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The objective of this study was to examine the correlation between serum interleukin-6 (IL-6) and IL-10 levels and outcome in chronic lymphocytic leukemia (CLL). Serum IL-6 and IL-10 levels were measured by enzyme-linked immunoabsorbent assays from 159 and 151 CLL patients, respectively, and from healthy control subjects (n = 55 [IL-6]; n = 37 [IL-10]). Cytokine levels were correlated with clinical features and survival. Serum IL-6 levels were higher in CLL patients (median, 1.45 pg/mL; range, undetectable to 110 pg/mL) than in control subjects (median, undetectable; range, undetectable to 4. 30 pg/mL) (P <.0001). Serum IL-10 levels were higher in CLL patients (median, 5.04 pg/mL; range, undetectable to 74 pg/mL) than in normal volunteers (median, undetectable; range, undetectable to 13.68 pg/mL) (P <.00001). Assays measuring both Epstein-Barr virus-derived and human IL-10 yielded higher values than assays measuring primarily human IL-10 (P <.05). Patients with elevation of serum IL-6 or IL-10 levels, or both, had worse median and 3-year survival (log rank P <.001) and unfavorable characteristics (prior treatment, elevated beta(2)-microglobulin or lactate dehydrogenase, or Rai stage III or IV). Elevated IL-6 and IL-10 levels were independent prognostic factors for survival when analyzed individually or in combination (Cox regression analysis). However, if beta(2)-microglobulin was incorporated into the analysis, it was selected as an independent prognostic feature, and IL-6/IL-10 were no longer selected. In patients with CLL, serum IL-6 and IL-10 (viral and human) levels are elevated and correlate with adverse disease features and short survival. In multivariate analysis, however, beta(2)-microglobulin is the most important prognostic factor. (+info)
Equivalent racial outcome after conformal radiotherapy for prostate cancer: a single departmental experience.
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PURPOSE: African-American (AA) men with prostate cancer present with advanced disease, relative to white (W) men. This report summarizes our clinical and biochemical control (bNED) rates after conformal radiotherapy (RT). In particular, we aim to characterize any race-based outcome differences seen after comparable treatment. PATIENTS AND METHODS: We reviewed 893 patients (418 AA and 475 W) with clinically localized prostate cancer treated between 1988 and 1997. Neoadjuvant hormonal blockade was used in 22.5% of cases, and all patients received conformal RT to a median dose of 68 Gy (range, 60 to 74.8 Gy). Biochemical failure was defined according to the American Society of Therapeutic Radiology and Oncology consensus definition. Median follow-up was 24 months (range, 1 to 114 months). RESULTS: The 5-year actuarial survival, disease-free survival, and bNED rates for the entire population were 80.5%, 70.0%, and 57.6%, respectively. When classified by prognostic risk category, the 5-year actuarial bNED rates were 78.7% for favorable, 57.7% for intermediate, and 39.8% for unfavorable category patients. AA men presented at younger ages and with more advanced disease. Controlled for prognostic risk category, AA and W men had similar 5-year actuarial bNED rates in favorable (78% v 79%, P: = .91), intermediate (52% v 62%, P: =.44), and unfavorable categories (36% v 45%, P: = .09). Race was not an independent prognostic factor (P: = .36). CONCLUSION: Conformal RT is equally effective for AA and W patients. More research is needed in order to understand and correct the advanced presentations in AA men. These data suggest a need for early screening in AA populations. (+info)
Phase II study of paclitaxel, ifosfamide, and cisplatin as second-line treatment in relapsed small-cell lung cancer.
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PURPOSE: The aim of the present phase II study was to evaluate the efficacy of the paclitaxel, ifosfamide, and cisplatin (PIC) combination in relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eligible patients were those with SCLC who had progressed or relapsed after therapy with carboplatin and etoposide (with or without chest radiotherapy). The PIC regimen consisted of paclitaxel 175 mg/m(2) on day 1, ifosfamide 5 g/m(2) divided over days 1 and 2, and cisplatin 100 mg/m(2) divided over days 1 and 2; PIC was given every 21 days with granulocyte colony-stimulating factor support. RESULTS: Thirty-three patients (30 men and three women) were entered onto the study (median age, 62 years [range, 55 to 70 years]; median performance status, 1 [range, 0 to 2]). Metastatic sites at study entry included the lymph nodes (n = 13 patients), bone (n = 9), liver (n = 5), brain (n = 6), lung nodules (n = 8), adrenal glands (n = 9), and other (n = 2) Responses included eight complete remissions and 16 partial remissions (overall response rate, 73% [24 of 33 patients]). Five patients had stable disease and two had progressive disease. Median time to progression and overall survival were 21 and 28 weeks, respectively. The 1-year survival rate was 12%, with two patients alive without evidence of disease at 76 and 104 weeks since PIC initiation. Grade 3 and 4 toxicities included neutropenia in 30 patients (24 [73%] developed grade 4 neutropenia [ < 5 days]) and febrile neutropenia in six patients (18%); grade 3 or 4 thrombocytopenia was seen in nine patients (27%). No grade 3 neuropathy was observed; grade 1 or 2 CNS toxicity was seen in five patients, there was no renal toxicity, grade 2 myalgias were seen in nine patients, grade 2 diarrhea was seen in one patient, and grade 3 nausea or vomiting was seen in seven patients. There were no treatment-related deaths. CONCLUSION: In the present phase II study, the PIC combination seemed highly active and tolerable in patients with relapsed SCLC when it was administered as second-line treatment. Given the present experience, an evaluation of the PIC regimen as front-line treatment of SCLC is planned. (+info)
What is changing in the natural history of chronic lymphocytic leukemia?
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BACKGROUND AND OBJECTIVES: In the last few years there has been a trend towards an improvement in overall survival of patients with chronic lymphocytic leukemia (CLL). Studies based on tumor registries of the general population or including patients referred to hematologic institutions have analyzed reasons for these changes. However, results need to be validated on independent series. DESIGN AND METHODS: We retrospectively evaluated 518 CLL patients diagnosed at our institution between January 1970 and December 1998. In this cohort of patients we looked at characteristics affecting natural history such as age and sex distribution, stage at diagnosis, survival probability and impact of the disease status on the actuarial survival. Trends in these variables were analyzed after splitting the whole series into three groups according to the period in which the diagnosis was made. Group I consisted of 75 patients diagnosed between 1970 and 1979, group II consisted of 149 patients diagnosed in the period 1980--1989, group III was composed of 293 patients diagnosed between 1991 and 1998. RESULTS: Age and sex distribution did not reflect different periods of diagnosis. The proportion of patients in whom diagnosis was established in low clinical stage (stage A) was higher in the group III (72%) than in groups I or II (26.3% and 50.3%, respectively) (p < 0.0001). Differences in the stage distribution affected life-expectancy which was longer for patients diagnosed in the nineties (median survival, 93 months) than in those diagnosed in the eighties (median survival, 54 months) or in the seventies (median survival, 38 months) (p < 0.0001). Finally, survival analyses by stage showed an improvement of life-expectancy when dealing with patients of high risk category (p =0.005). INTERPRETATION AND CONCLUSIONS: CLL patients diagnosed in the last decade enjoy the best clinical outcome, mostly as a result of a greater proportion of patients in the low-risk clinical stage and a relatively longer survival of the high risk group. It is not clear whether these changes represent true modifications of the natural history of CLL. At the beginning of the third millennium CLL continues to be a fatal disease with a significant impact on life-expectancy. (+info)
The number of donor CD3(+) cells is the most important factor for graft failure after allogeneic transplantation of CD34(+) selected cells from peripheral blood from HLA-identical siblings.
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This study analyzed the characteristics of 257 HLA-identical sibling transplants of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells depleted of T cells by CD34(+) positive selection (allo-PBT/CD34(+)) for their effect on the incidence of graft failure. Twenty-four patients developed graft failure (actuarial probability, 11%; 95% confidence interval, 7.1-14. 9). Prognostic factors considered were sex and age of donor and recipient, donor-recipient blood group compatibility, diagnosis, disease status at transplant, conditioning regimen, cytomegalovirus serology, number of CD34(+) and CD3(+) cells infused, and cryopreservation. The major factor associated with graft failure was the number of CD3(+) cells in the inoculum. Twenty-three of 155 patients receiving a T-cell dose in the graft less than or equal to 0.2 x 10(6)/kg experienced graft failure, compared with only one of 102 patients receiving more than 0.2 x 10(6)/kg (actuarial probability 18% vs 1%, respectively; P =.0001). The actuarial probability of graft failure progressively increased as the number of CD3(+) cells in the graft decreased, which was determined by grouping the number of CD3(+) cells in quartiles (log-rank P =.03; log-rank for trend P =.003). In the multivariate analysis by the proportional hazard method, 2 covariates entered into regression at a significant level: CD3(+) cells less than or equal to 0.2 x 10(6)/kg (risk ratio = 17; P <.0001), and patients with chronic myelogenous leukemia (CML) conditioned with busulphan-based regimens (risk ratio = 4.8; P =.001). From these results it appears that the number of CD3(+) cells in the inoculum-with a threshold of 0.2 x 10(6)/kg or less-is the most critical factor in maintaining a sustained engraftment in allo-PBT/CD34(+) from HLA-identical siblings. In addition, for patients with CML receiving 0.2 x 10(6)/kg or less CD3(+) cells, total body irradiation might be better than busulphan-based regimens. (+info)
Raised blast glutathione levels are associated with an increased risk of relapse in childhood acute lymphocytic leukemia.
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A preliminary study has linked raised blast glutathione levels with chemoresistance in acute myeloid and lymphoblastic leukemia in adults and children. In this study, therefore, the relationship between leukemic blast glutathione levels and prognosis in childhood acute lymphoblastic leukemia (ALL) was investigated. A total of 77 childhood ALL samples were analyzed, 62 at initial presentation and 15 at relapse. A 20-fold interindividual variation in glutathione levels at presentation (median, 6.54 nmol/mg protein; range, 1.37 to 27.9) was demonstrated. The median level in T-lineage ALL was 2. 3-fold higher than in B-lineage ALL (Mann-Whitney test, P <.0001). There was a significant correlation between presenting white cell count (WBC) and glutathione level (Spearman rank correlation coefficient, rho = 0.45, P =.001). A high DNA index correlated with low glutathione levels (Mann-Whitney test, P =.013). There was no significant relationship between glutathione levels and in vitro drug sensitivity. Patients with glutathione levels above the median had a significantly greater risk of relapse (log-rank test statistic, 5.55; P =.018), and the overall survival rate was significantly reduced (log-rank test statistic, 4.38; P =.04). Multivariate analysis demonstrated that glutathione concentration was of independent prognostic value when assessed in conjunction with age, gender, WBC, and immunophenotype. The association of elevated blast glutathione levels with an increased risk of relapse suggests that glutathione-depleting agents may be of therapeutic value in patients who present with a high WBC. (+info)
High-dose therapy and autologous bone marrow transplantation for follicular lymphoma in first complete or partial remission: results of a phase II clinical trial.
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Advanced stage follicular small cleaved and mixed cell lymphoma is characterized by relapse from remission and survival ranging from 6 to 12 years. Because young patients have the greatest compromise in longevity, the efficacy and toxicity of high-dose radiochemotherapy and bone marrow transplantation after conventional chemotherapy was evaluated in a prospective phase II clinical trial. Thirty-seven patients in a minimal disease state after conventional chemotherapy received fractionated total body irradiation and high-dose etoposide and cyclophosphamide, followed by purged autologous bone marrow. A reference sample of 188 patients of similar age, stage, and histology managed at this institution before 1988 was identified for comparison of patient characteristics and outcomes. Compared with reference patients, transplant recipients had a higher tumor burden at diagnosis. With a median follow-up of 6.5 years, the estimated 10-year survival after transplantation was 86%. There was a single lymphoma death yielding a 10-year disease-specific survival of 97%. There were 2 early transplant-related deaths and 2 late acute leukemia deaths. Ten patients relapsed, one with microscopic disease only. High tumor burden at diagnosis and incomplete response to chemotherapy adversely influenced survival in the reference but not in the transplanted patients. The estimated risk of death of 14% and relapse of 30% at 10 years in our transplanted follicular lymphoma patients, the majority of whom had high tumor burdens, compares favorably with our observations in appropriately matched reference patients. (+info)