Stem cell transplantation: risk factors for psychiatric morbidity

The aim of this study was to determine the risk factors for psychiatric disorder in haematological cancer patients during hospitalization for stem cell transplantation. In this 3-year prospective study, 220 patients received stem cell transplantation at a single institution. Structured psychiatric interviews applying standardized diagnostic criteria were performed at hospital admission and weekly during hospitalization until discharge or death, yielding a total of 1,062 interviews. Psychiatric disorder (any depressive, anxiety, or adjustment disorder) prevalence at the time of hospital admission was 21% and psychiatric disorder incidence during post-admission follow-up was 22%. After adjusting for multiple confounders in multivariate logistic regression analyses, we found that younger age, women, a past psychiatric history, lower functional status, pain, smoking cessation, and higher regimen-related toxicity were significantly associated with psychiatric disorder risk. Our study findings may help to improve identification of the patients most at risk for psychiatric disturbances during hospitalization for stem cell transplantation.     

Predictors of viridans streptococcal shock syndrome in bacteremic children with cancer and stem-cell transplant recipients.

PURPOSE: To describe episodes of viridans streptococcal bacteremia (VSB) in a cohort of children with cancer and stem-cell transplant (SCT) recipients and to determine predictors of viridans streptococcal shock syndrome (VSSS) in this group of children. PATIENTS AND METHODS: For this retrospective review, we included episodes of VSB isolated between March 1997 and September 2002, in children (相似文献   

Role of depression as a predictor of mortality among cancer patients after stem-cell transplantation.

PURPOSE: To determine the association between depression and survival among cancer patients at 1, 3, and 5 years after stem-cell transplantation (SCT). PATIENTS AND METHODS: This was a prospective cohort study of 199 hematologic cancer patients who survived longer than 90 days after SCT and who were recruited in a University-based hospital between July 1994 and August 1997. Patients received a psychiatric assessment at four consecutive time points during hospitalization for SCT, yielding a total of 781 interviews. Depression diagnoses were determined on the basis of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. RESULTS: Eighteen (9.0%) and 17 patients (8.5%) met criteria for major and minor depression, respectively. Multivariate Cox regression models found major depression to be predictive of higher 1-year (hazard ratio [HR], 2.59; 95% CI, 1.21 to 5.53; P = .014) and 3-year mortality (HR, 2.04; 95% CI, 1.03 to 4.02; P = .041) but not 5-year mortality (HR, 1.48; 95% CI, 0.76 to 2.87; P = .249). Minor depression had no effect on any mortality outcome. Other multivariate significant predictors of higher mortality were higher regimen toxicity in the 1-, 3-, and 5-year models; older age and acute lymphoblastic leukemia in the 3- and 5-year models; chronic myelogenous leukemia in the 3-year model; and lower functional status and intermediate/higher risk status in the 5-year model. Use of peripheral-blood stem cells predicted lower mortality in the 5-year model. CONCLUSION: After adjusting for multiple factors, major depression predicted higher 1- and 3-year mortality among cancer patients after SCT, underscoring the importance of adequate diagnosis and treatment of major depression.     

Trends in the aggressiveness of cancer care near the end of life.

PURPOSE: To characterize the aggressiveness of end-of-life cancer treatment for older adults on Medicare, and its relationship to the availability of healthcare resources. PATIENTS AND METHODS: We analyzed Medicare claims of 28,777 patients 65 years and older who died within 1 year of a diagnosis of lung, breast, colorectal, or other gastrointestinal cancer between 1993 and 1996 while living in one of 11 US regions monitored by the Surveillance, Epidemiology, and End Results Program. RESULTS: Rates of treatment with chemotherapy increased from 27.9% in 1993 to 29.5% in 1996 (P =.02). Among those who received chemotherapy, 15.7% were still receiving treatment within 2 weeks of death, increasing from 13.8% in 1993 to 18.5% in 1996 (P <.001). From 1993 to 1996, increasing proportions of patients had more than one emergency department visit (7.2% v 9.2%; P <.001), hospitalization (7.8% v 9.1%; P =.008), or were admitted to an intensive care unit (7.1% v 9.4%; P =.009) in the last month of life. Although fewer patients died in acute-care hospitals (32.9% v 29.5%; P <.001) and more used hospice services (28.3% v 38.8%; P <.001), an increasing proportion of patients who received hospice care initiated this service only within the last 3 days of life (14.3% v 17.0%; P =.004). Black patients were more likely than white patients to experience aggressive intervention in nonteaching hospitals but not in teaching hospitals. Greater local availability of hospices was associated with less aggressive treatment near death on multivariate analysis. CONCLUSION: The treatment of cancer patients near death is becoming increasingly aggressive over time.     

Clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma: a study of a prospective cohort.

PURPOSE: This study aims to clarify the clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The clinicopathologic features of 5-year survivors and disease-free survivors were elucidated in a cohort of 230 patients prospectively observed for > 5 years (64 to 192 months) after curative resection of HCC. RESULTS: The incidence of 5-year overall and disease-free survivors were 37% (85 of 230) and 20% (45 of 230), respectively. Clinicopathologic features associated with 5-year survivors included female sex (P =.024), preoperative serum albumin > or= 40 g/L (P =.033), AST < 50 u/L (P =.001), tumor < 5 cm (P =.001), solitary tumor (P =.035), encapsulated tumor (P =.021), no venous invasion (P =.001), no microsatellite nodule (P =.001), and early pathologic tumor-node-metastasis (pTNM) stage (I or II, P <.001). Features favoring 5-year disease-free survivors were preoperative serum AST < 50 u/L (P =.007), tumor < 5 cm (P =.005), encapsulated tumor (P =.007), no venous invasion (P <.001), no microsatellite nodule (P =.001), and early pTNM stage (I or II, P <.001). By multivariate analysis, pTNM stage was the only significant predictive factor for both overall and disease-free survival. CONCLUSION: This study shows that long-term disease-free survival > 5 years after resection of HCC can be achieved in patients with favorable tumor characteristics. Early pTNM stage was the most reliable predictor of both long-term overall and disease-free survivors.     

Defining cancer patients as being in the terminal phase: who receives a formal diagnosis, and what are the effects?

PURPOSE: Physicians either do not define cancer patients as being terminal, or their prognostic estimates tend to be optimistic. This might affect patients' appropriate and timely referral to specialist palliative care services or can lead to unintended acute hospitalization. PATIENTS AND METHODS: We used the Danish Cancer Register and four administrative registers to perform a retrospective cohort study in 3,445 patients who died as a result of cancer. We used the Danish "terminal declaration" issued by a physician as a proxy for a formal terminal diagnosis (prognosis of death within 6 months). The terminal declaration gives right to economic benefits and increased care for the dying. We investigated patient-related factors of receiving an explicit terminal diagnosis by logistic regression and then analyzed the effects of such a diagnosis on admission rate per week and place of death. RESULTS: Thirty-four percent of patients received a formal terminal diagnosis. Age of > or = 70 years (odds ratio [OR], 0.44; 95% CI, 0.34 to 0.56; P < .001), women (OR, 0.81; 95% CI, 0.69 to 0.96; P = .02), hematologic cancer (OR, 0.20; 95% CI, 0.09 to 0.41; P < .001), and a less than 1-month survival time (OR, 0.10; 95% CI, 0.07 to 0.15; P < .001) were associated with a lesser likelihood of receiving a formal terminal diagnosis. Explicit terminal diagnosis was associated with lower admission rate and an adjusted OR of hospital death of 0.25 (95% CI, 0.21 to 0.29). CONCLUSION: Women and the elderly were less likely to receive a formal terminal diagnosis. The formal terminal diagnosis reduced hospital admissions and increased the possibilities of dying at home.     

Viable malignant cells after primary chemotherapy for disseminated nonseminomatous germ cell tumors: prognostic factors and role of postsurgery chemotherapy--results from an international study group.

PURPOSE: To assess the value of postsurgery chemotherapy in patients with disseminated nonseminomatous germ-cell tumors (NSGCTs) and viable residual disease after first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: The outcome of 238 patients was reviewed. Tumor markers had normalized in all patients before resection. A multivariate analysis of survival was performed on 146 patients. RESULTS: The 5-year progression-free survival (PFS) rate was 64% and the 5-year overall survival (OS) rate was 73%. Three factors were independently associated with both PFS and OS: complete resection (P <.001), < 10% of viable malignant cells (P =.001), and a good International Germ Cell Consensus Classification (IGCCC) group (P =.01). Patients were assigned to one of three risk groups: those with no risk factors (favorable group), those with one risk factor (intermediate group), and those with two or three risk factors (poor-risk group). The 5-year OS rate was 100%, 83%, and 51%, respectively (P <.001). The 5-year PFS rate was 69% (95% confidence interval [CI], 62% to 76%) and 52% (95% CI, 40% to 64%) in postoperative chemotherapy recipients and nonrecipients, respectively (P <.001). No significant difference was detected in 5-year OS rates. After adjustment on the three prognostic factors, postoperative chemotherapy was associated with a significantly better PFS (P <.001) but not with better OS. Patients in the favorable risk group had a 100% 5-year OS, with or without postoperative chemotherapy. Postoperative chemotherapy appeared beneficial in both PFS (P <.001) and OS (P =.02) in the intermediate-risk group but was not statistically beneficial in the poor-risk group. CONCLUSION: A complete resection may be more critical than recourse to postoperative chemotherapy in the setting of postchemotherapy viable malignant NSGCT. Immediate postoperative chemotherapy or surveillance alone with chemotherapy at relapse may be reasonable options depending on the completeness of resection, IGCCC group, and percent of viable cells. Validation is necessary.     

Hyperglycemia in patients with acute myeloid leukemia is associated with increased hospital mortality

BACKGROUND: Hyperglycemia is often observed in medically ill patients. Previous studies have shown that patients with hyperglycemia during induction therapy for acute lymphoblastic leukemia develop more infections and have shorter disease-free survival. The authors hypothesized that hyperglycemia may be associated with adverse outcomes in patients with acute myeloid leukemia (AML) and sought to determine whether this association exists in this population. METHODS: The authors performed a retrospective cohort study to examine the relation between hyperglycemia and hospital mortality in patients with the diagnosis of AML. Two hundred eighty-three adult patients were treated over a 3-year period. All hospitalizations were reviewed during the study period, and glucose exposure and outcomes were quantified. RESULTS: Hyperglycemia during a patient's hospitalization was associated with increased hospital mortality (OR, 1.38; 95% CI, 1.23-1.55; P < .001) after adjusting for covariates, including disease state, treatment type, and response. The rise in mortality was evident at even mild levels (110-150 mg/dL) of glucose elevation. Although the odds of developing severe sepsis (OR, 1.24; 95% CI, 1.13.-1.38; P < .001) or severe sepsis with respiratory failure (OR, 2.04; 95% CI, 1.44-2.91; P < .001) were increased with hyperglycemia, sepsis did not appear to be the main factor responsible for the negative impact of hyperglycemia on hospital mortality. CONCLUSIONS: This study demonstrated an association between hospital mortality and even modest levels of hyperglycemia in AML patients. Prospective studies are needed to confirm this association and to discern causal pathways that mediate this effect.     

Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial.

PURPOSE: In a series of trials, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV) have been identified as effective treatments for Hodgkin's disease. We compared these regimens as initial chemotherapy for Hodgkin's disease. PATIENTS AND METHODS: Adult patients (N = 856) with advanced Hodgkin's disease were randomly assigned to treatment with ABVD or MOPP/ABV. The major end points were failure-free and overall survival, life-threatening acute toxicities, and serious long-term toxicities, including cardiomyopathy, pulmonary toxicity, myelodysplastic syndromes (MDS), and secondary malignancies. RESULTS: The rates of complete remission (76% v 80%, P =.16), failure-free survival at 5 years (63% v 66%, P =.42), and overall survival at 5 years (82% v 81%, P =.82) were similar for ABVD and MOPP/ABV, respectively. Clinically significant acute pulmonary and hematologic toxicity were more common with MOPP/ABV (P =.060 and.001, respectively). There was no difference in cardiac toxicity. There were 24 deaths attributed to initial treatment: nine with ABVD and 15 with MOPP/ABV (P =.057). There have been 18 second malignancies associated with ABVD and 28 associated with MOPP/ABV (P =.13). Thirteen patients have developed MDS or acute leukemia: 11 were initially treated with MOPP/ABV, and two were initially treated with ABVD but subsequently received MOPP-containing regimens and radiotherapy before developing leukemia (P =.011). CONCLUSION: ABVD and the MOPP/ABV hybrid are effective therapies for Hodgkin's disease. MOPP/ABV is associated with a greater incidence of acute toxicity, MDS, and leukemia. ABVD should be considered the standard regimen for treatment of advanced Hodgkin's disease.     

Complementary therapies for children undergoing stem cell transplantation

BACKGROUND:

Children undergoing stem cell transplant (SCT) experience high levels of somatic distress and mood disturbance. This trial evaluated the efficacy of complementary therapies (massage, humor therapy, relaxation/imagery) for reducing distress associated with pediatric SCT.

METHODS:

Across 4 sites, 178 pediatric patients scheduled to undergo SCT were randomized to a child‐targeted intervention involving massage and humor therapy, the identical child intervention plus a parent intervention involving massage and relaxation/imagery, or standard care. Randomization was stratified by site, age, and type of transplant. The interventions began at admission and continued through SCT Week +3. Primary outcomes included patient and parent reports of somatic distress and mood disturbance obtained weekly from admission through Week +6 using the Behavioral, Affective, and Somatic Experiences Scales. Secondary outcomes included length of hospitalization, time to engraftment, and usage of narcotic analgesic and antiemetic medications.

RESULTS:

A mixed model approach was used to assess longitudinal trends of patient and parent report outcomes and to test differences between groups on these measures. Significant changes across time were observed on all patient and parent report outcomes. However, no significant differences between treatment arms were found on the primary outcomes. Similarly, no significant between‐group differences were noted on any of the medical variables as secondary outcomes.

CONCLUSIONS:

Results of this multisite trial failed to document significant benefits of complementary interventions in the pediatric SCT setting. Cancer 2010. © 2010 American Cancer Society.     

Relapse of TEL-AML1--positive acute lymphoblastic leukemia in childhood: a matched-pair analysis.

PURPOSE: The aim of this study was to investigate whether, in relapsed childhood acute lymphoblastic leukemia (ALL), the frequent genetic feature of TEL-AML1 fusion resulting from the cryptic chromosomal translocation t(12;21)(p13;q22) is an independent risk factor. PATIENTS AND METHODS: A matched-pair analysis was performed within a homogeneous group of children with first relapse of BCR-ABL-negative B-cell precursor (BPC) ALL treated according to relapse trials ALL-Rezidiv (REZ) of the Berlin-Frankfurt-Münster Study Group. A total of 249 patients were eligible for this study: 53 (21%) were positive for TEL-AML1, and 196 (79%) were negative. Positive patients were matched for established most-significant prognostic determinants at relapse, time point, and site of relapse, as well as age and peripheral blast cell count at relapse. RESULTS: Fifty pairs matching the aforementioned criteria could be determined. The probabilities with SE of event-free survival and survival at 5 years for matched TEL-AML1 positives and negatives are 0.63 +/- 0.10 versus 0.38 +/- 0.10 (P =.09) and 0.82 +/- 0.09 versus 0.42 +/- 0.19 (P =.10), respectively. These results were confirmed by multivariate analysis, revealing an independent prognostic significance of time point and site of relapse (both P <.001) but not of TEL-AML1 expression (P =.09). CONCLUSION: TEL-AML1 expression does not constitute an independent risk factor in relapsed childhood BCP-ALL after matching for relevant prognostic parameters. It undoubtedly characterizes genetically an ALL entity associated with established favorable prognostic parameters. High-risk therapeutic procedures such as allogeneic SCT should be considered restrictively.     

Association of preoperative plasma levels of vascular endothelial growth factor and soluble vascular cell adhesion molecule-1 with lymph node status and biochemical progression after radical prostatectomy.

PURPOSE: Angiogenesis is a critical process for cancer progression. We tested whether elevated circulating levels of the angiogenesis-related markers vascular endothelial growth factor (VEGF) and/or soluble vascular cell adhesion molecule-1 (sVCAM-1) are associated with prostate cancer diagnosis, stage, progression, and metastasis. PATIENTS AND METHODS: Plasma levels of VEGF and sVCAM-1 were measured on frozen, archival plasma obtained preoperatively from 215 consecutive patients who underwent radical prostatectomy for clinically localized disease, nine men with untreated prostate cancer metastatic to bones, and 40 healthy men without cancer. RESULTS: Plasma levels of both VEGF and sVCAM-1 were highest in patients with bone metastases (P <.001). VEGF levels were higher in patients with clinically localized disease than in healthy controls (P <.001). VEGF levels were elevated in patients with biopsy and final Gleason sum > or = 7 (P =.036 and P =.020, respectively) and extraprostatic extension (P =.047). Higher preoperative VEGF was independently associated with metastases to lymph nodes (P <.001). Both VEGF and sVCAM-1 were independently associated with biochemical progression after adjustment for the effects of standard preoperative features (P =.014 and P =.039, respectively). VEGF remained independently associated with biochemical progression after adjustment for standard postoperative features (P =.019). CONCLUSION: Plasma levels of VEGF increased incrementally from healthy controls to patients with clinically localized disease to patients with lymph node and skeletal metastases. Higher preoperative VEGF was independently associated with metastases to lymph nodes and biochemical progression after surgery in both pre- and postoperative models. Plasma sVCAM-1 was elevated in men with bone metastases and was associated with biochemical progression in a preoperative model.     

High survival rate in infant acute leukemia treated with early high-dose chemotherapy and stem-cell support. Groupo Espa?ol de Trasplante de Médula Osea en Ni?os.

PURPOSE: Infants with acute leukemia have a poor prognosis when treated with conventional chemotherapy. It is still unknown if stem-cell transplantation (SCT) can improve the outcome of these patients. In the present study, we review our experience with SCT in infant acute leukemia to clarify this issue. PATIENTS AND METHODS: We report the results of 26 infants who were submitted to a SCT for acute leukemia. There were 15 cases of acute myeloid leukemia and 10 cases of acute lymphoid leukemia. One patient had a bilineal leukemia. Twenty-two patients were in their first complete response (CR1), three were in their second CR, and one was in relapse. Eight patients were submitted to allogeneic SCT, and 18 underwent autologous SCT. RESULTS: With a median follow-up of 67 months, the 5-year overall survival and disease-free survival (DFS) are 64% (SE = 9%) and 63% (SE = 10%), respectively. Autologous and allogeneic SCT offered similar outcome. There was not any transplant-related mortality, and all deaths were caused by relapse in the first 6 months after SCT. In multivariate analysis, the single factor associated with better DFS was an interval between CR1 and SCT of less than 4 months (P: <.025). CONCLUSION: SCT is a valid option in the treatment of infant acute leukemia, and it may overcome the high risk of relapse with conventional chemotherapy showing very reduced toxicity. This study suggests that SCT should be performed in CR1 in the early phase of the disease.     

Increased age at diagnosis has a significantly negative effect on outcome in children with Down syndrome and acute myeloid leukemia: a report from the Children's Cancer Group Study 2891.

PURPOSE: To determine the outcome of children with Down syndrome (DS) and acute myeloid leukemia (AML) receiving standard timing chemotherapy without bone marrow transplantation (BMT), with determination of prognostic factors. PATIENTS AND METHODS: Children with DS and newly diagnosed AML or myelodysplasia were prospectively enrolled on Children's Cancer Group study 2891 (N = 161) and treated uniformly with four standard timing induction courses of dexamethasone, cytarabine arabinoside, 6-thioguanine, etoposide, daunorubicin (DCTER) followed by intensively timed high-dose cytarabine. RESULTS: Children with DS were significantly younger at diagnosis than those without (median age, 1.8 v 7.5 years, respectively; P <.001), with more megakaryocytic leukemia (70% v 6%; P <.001). Higher complete remission rates (91%) were achieved in children with DS than among those without DS (75%; P <.001). Equivalent grade 3 to 4 toxicity (29% v 30%; P =.84) was seen, though children with DS had greater pulmonary toxicity (P <.01) during induction and mucositis during intensification (P =.12). Children with DS had significantly better 8-year event-free survival (EFS; 77% v 21% standard and 40% intensive induction; P <.0001). Multivariate analysis in children with DS revealed that only age at diagnosis of 2 years or older was a risk factor for greater relapse risk (odds ratio, 4.9; P =.006) and worse survival. Children between ages 0 to 2 years (n = 94) had a 6-year EFS of 86%; those from 2 to 4 years (n = 58), 70%; and those older than 4 years (n = 9), 28%. Remission failures were the primary reason for worse 6-year EFSs (1% in those 0 to 2 years v 14% if >2 years; P =.002). CONCLUSION: Outcome for children with DS and AML is excellent with standard induction therapy, but declines with increasing age.     

Psychiatric disorders following first breast cancer recurrence: prevalence, associated factors and relationship to quality of life

OBJECTIVE: The purpose of this study was to investigate the prevalence of and factors associated with psychiatric disorders and the impact on quality of life (QOL) in patients with first breast cancer recurrence. METHODS: We analyzed the baseline data on 50 consecutively enrolled recurrent breast cancer patients, participating in a feasibility study of multifaceted psychosocial intervention. Psychiatric disorders, including major depressive disorder (MDD), dysthymic disorder, panic disorder, post-traumatic stress disorder (PTSD), generalized anxiety disorder and adjustment disorders (AD), were evaluated according to the Structured Clinical Interview for the DSM-III-R and IV. The patients' demographic data, biomedical factors, social support, mental adjustment to cancer, personality traits and QOL were also evaluated. RESULTS: Eleven (22%) met the DSM-III-R and IV criteria for MDD, PTSD or AD (MDD, 2%; PTSD, 2%; AD, 20%). Univariate analysis indicated that current doxorubicin/cyclophosphamide, presence of a confidant, past history of MDD, helplessness/hopelessness and neuroticism were significantly associated with psychiatric disorders. On multivariate logistic regression analysis, past history of MDD and helplessness/hopelessness were significant associated factors. Psychiatric disorders were significantly associated with lower functional scales ('emotional functioning', 'body image' and 'future perspective') and higher symptom scales ('appetite loss', 'diarrhea', 'fatigue' and 'nausea-vomiting') in QOL. CONCLUSIONS: The result suggests that asking about history of depression and appropriate intervention, including psycho-education, are needed for patients with first breast cancer recurrence in order to detect and manage psychological distress. Although further studies are needed to clarify causal links between psychiatric disorders and QOL, patients' psychiatric disorders were associated with QOL.     

Clinical factors associated with fatigue in haematologic cancer patients receiving stem-cell transplantation

We have evaluated risk factors associated with fatigue in 220 cancer patients during hospitalization for stem-cell transplantation (SCT). Fatigue was assessed using a validated one-item energy scale and a comprehensive set of fatigue predictors, at hospital admission (baseline), day of SCT, and 7 days and 14 days after SCT. In cross-sectional multivariate analysis, depression was the variable most consistently and strongly associated with fatigue; other factors significantly associated with fatigue at some time during the study included older age, higher education, smoking, lower Karnofsky performance status, loss of appetite, nausea/vomiting, pain, higher regimen-related toxicity, low hemoglobin level, requirement for red blood-cell transfusions, and third year of the study period. In prospective multivariate analysis, baseline depression showed significance or a trend towards significance in its ability to predict subsequent measures of fatigue during hospitalization. Our findings may help to shed light on the mechanisms underlying fatigue and may also guide future interventions.     

Intensification of mercaptopurine/methotrexate maintenance chemotherapy may increase the risk of relapse for some children with acute lymphoblastic leukemia.

PURPOSE: Thioguanine nucleotides (TGNs) mediate the cytotoxicity of mercaptopurine (MP). Methylated MP metabolites (formed by thiopurine methyltransferase [TPMT]) and methotrexate (MTX) polyglutamates can inhibit de novo purine synthesis. We explored whether dose adjustment of MP and MTX by erythrocyte (E) levels of TGN and MTX (including polyglutamates) could improve outcome in childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: A total of 538 children with ALL were randomly assigned to have their oral MP/MTX maintenance therapy adjusted by white cell counts (WBC), E-TGN, and E-MTX (pharmacology group), or by WBC only (control group). RESULTS: After a median follow-up of 7.8 years, 79 patients had relapsed. Cox regression analysis showed an increased risk of relapse for boys (P =.00003), high WBC at diagnosis (P =.03), pharmacology arm (6.6 times increased relapse hazard for girls), high TPMT activity (P =.002), and high average neutrophil counts during maintenance therapy (P =.0009), with a significant interaction between sex and randomization group (P =.0007). For girls, the relapse risk was 5% in the control group and 19% in the pharmacology group (P =.001) because of an increased relapse hazard during the first year after cessation of therapy. TPMT activity was the most significant predictor of relapses among girls in the pharmacology arm (P <.0001). Overall, the TPMT activity was higher for patients who relapsed after cessation of therapy compared with those who stayed in remission (girls 19.5 v 17.4 U/mL, P =.03; boys 19.3 v 18.0 U/mL, P =.04). CONCLUSION: Adding pharmacologically guided treatment intensification to dose adjustments by blood counts may not be warranted for girls, whereas new approaches to optimize maintenance therapy are needed for boys.     

Transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical siblings in adult patients with acute myeloid leukemia and acute lymphoblastic leukemia.

PURPOSE: Several studies show that allogeneic peripheral blood stem cells (PBSCs) engraft more rapidly than bone marrow (BM). However, the data are inconsistent with regard to acute and chronic graft-versus-host disease (GVHD), relapse, transplant-related mortality (TRM), and leukemia-free survival (LFS). PATIENTS AND METHODS: Between January 1994 and December 2000, 3,465 adult patients (older than 15 years of age) were reported to the European Group for Blood and Marrow Transplantation Registry from 224 centers. Among acute myeloid leukemia (AML) patients, 1,537 patients received BM and 757 patients received PBSC. In acute lymphoblastic leukemia (ALL) patients, the corresponding figures were 826 versus 345 patients who were analyzed for engraftment, GVHD, TRM, relapse, LFS, and survival. RESULTS: In multivariate analysis, the recovery of neutrophils and platelets was faster with PBSC than with BM (P <.0001). Chronic GVHD was associated with PBSC in patients with AML (relative risk [RR], 2.11; 95% confidence interval, 1.66 to 2.7; P <.0001) and ALL (RR, 1.56; 95% confidence interval, 1.09 to 2.27; P =.02). PBSC versus BM in patients with AML or ALL was not significantly associated with acute GVHD, TRM, relapse, survival, or LFS. In multivariate analysis of patients with AML, factors significantly associated with improved LFS included first remission at transplant (P <.0001), promyelocytic leukemia (M3) versus other French-American-British types (P <.0001), and donor age below median 37 years (P =.02). In patients with ALL, first remission (P <.0001) and methotrexate included in the immunosuppressive regimen (P =.001) were associated with improved LFS. CONCLUSION: Allogeneic PBSC results in faster neutrophil and platelet engraftment and a higher incidence of chronic GVHD than BM. However, acute GVHD, TRM, relapse, survival, and LFS were similar in patients receiving PBSCs versus BM.     

Infections and association with different intensity of chemotherapy in children with acute myeloid leukemia

BACKGROUND:

The objectives were to compare infections during different intensities of therapy in children with acute myeloid leukemia (AML).

METHODS:

Subjects were children enrolled in Children's Cancer Group 2891 with AML. In phase 1 (induction), patients were randomized to intensive or standard timing. In phase 2 (consolidation), those with a family donor were allocated allogeneic stem cell transplantation (SCT); the remainder were randomized to autologous SCT or chemotherapy. This report compares infections between different treatments on an intent‐to‐treat basis.

RESULTS:

During phase 1, intensive timing was associated with more bacterial (57.7% vs 39.4%; P < .001), fungal (27.4% vs 9.9%; P < .001), and viral (14.0% vs 3.9%; P < .001) infections compared with standard timing. During phase 2, chemotherapy was associated with more bacterial (56.5% vs 40.1%; P = .005), but similar fungal (9.5% vs 6.1%; P = 1.000) and viral (4.2% vs 12.9%; P = .728) infections compared with allogeneic SCT. No differences between chemotherapy and autologous SCT infections were seen. Fatal infections were more common during intensive compared with standard timing induction (5.5% vs 0.9%; P = .004). Infectious deaths were similar between chemotherapy, autologous SCT, and allogeneic SCT.

CONCLUSIONS:

Prevalence of infection varies depending on the intensity and type of treatment. This information sheds insight into the mechanisms behind susceptibility and outcome of infections in pediatric AML. Cancer 2009. © 2009 American Cancer Society.