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Oral therapies have become a common treatment choice for several lymphoid cancers. While therapeutic efficacy and patient preference for this therapy type have been reported, there is a lack of knowledge about its effectiveness for lymphoma in clinical practice, particularly in regard to the effects of medication nonadherence. While studies of oral medications in other diseases have shown that adherence is a major factor in outcomes and costs, there is scant research investigating adherence specifically in lymphoma patients, who face unique challenges in their diseases and treatments. To address the limited data available, we constructed a conceptual model and highlighted key opportunities for future research to better elucidate oral therapy adherence in lymphoma. This research will hopefully improve understanding and efficacy of oral treatment for lymphoma patients, while also informing other cancers utilizing oral therapies currently and in the future.

Myeloid/lymphoid neoplasms with FGFR1 rearrangement are a rare entity. We present a multicenter experience of 17 patients with FISH-confirmed FGFR1 rearrangement. The clinical presentation at diagnosis included myeloproliferative neoplasm (MPN) in 4 (24%) patients, acute leukemia (AL) in 7 (41%), and concomitant MPN with AL in 6 (35%). The two most frequently observed cytogenetic abnormalities were t(8;13)(p11.2;q12)(partner gene ZMYM2) and t(8;22)(p11.2; q11.2)(BCR). Seventy-eight percent of tested patients had a RUNX1 mutation, of whom all had AL. Overall response rate to frontline therapy was 69%, and 76% of patients subsequently received allogeneic stem cell transplant (ASCT). After a median follow-up of 11 months, median progression-free survival was 15 months and median overall survival was not reached. In conclusion, FGFR1-rearranged hematologic malignancies present with features of MPN and/or AL. FGFR1 and RUNX1 are therapeutic targets for ongoing and future clinical trials.

The role of HLA system in allogeneic haematopoietic stem cell transplantation (allo-HSCT) outcome is unarguable. In this study we investigated association of HLA-A,-B and-DRB1 alleles with overall survival (OS) in 186 patients undergoing allo-HSCT for lymphoid malignancies. Analyses confirmed significantly better OS for HLA-DRB1∗04 carriers compared with non-carriers (p = 0.01). Survival benefit was confined to male patients (in multivariate analyses p = 0.034, hazard ratio 0.35, 95% confidence interval 0.13-0.92), whereas in females no difference was noted (p = 0.82). Furthermore, donor gender also affected outcome and transplantation from female HLA-DRB1∗04 carrier donors resulted in superior survival compared with female non-carrier donors (p = 0.01). Combined analyses including recipient/donor gender and HLA-DRB1∗04 showed that survival of male patients varied significantly according to donor gender and HLA-DRB1∗04 carriership (p = 0.04) with best survival among HLA-DRB1∗04 carriers transplanted from female donors. Of relevance to our results, HLA-DRB1∗04 has been documented as risk allele group for lymphoid malignancies, and studies described a male-specific risk. We believe that our findings provide further supporting evidence for sex-specific alterations secondary to HLA-DRB1∗04 or related genes. Further studies are warranted to evaluate whether in contrast to general favour of male donors HLA-DRB1∗04 carrier patients with lymphoid malignancies could benefit from transplantation from female donors., (Copyright © 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Introduction: Bendamustine, typically in combination with rituximab, is an effective treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma. Despite its acceptable short-term toxicity profile, long-term toxicities are less well established. This study investigated the long-term adverse effects of bendamustine and responses to subsequent treatments., Patients and Methods: Charts of 194 patients were retrospectively reviewed; 54% had received prior treatment (76% attained complete response [CR] or partial response [PR])., Results: Patients who did not achieve a CR or PR did not respond well to subsequent treatments. Malignancies following bendamustine were diagnosed in 11% (21) of patients (first line [7] and salvage [14]), including squamous (8) or basal cell (4) skin cancers; prostate cancer (3), renal cancer (3), bladder cancer (2), melanoma (2), lung cancer (1), and histiocytic sarcoma (1). There were no occurrences of therapy-related myelodysplastic syndrome or acute myelogenous leukemia reported. Infections occurred in 63% of patients; however, no deaths were attributable to bendamustine., Conclusion: Bendamustine is an effective therapy with limited long-term sequelae in patients with lymphoid malignancies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To investigate the dynamic change of follicular T helper cells (T FH ) in patients with malignant lymphoid disease (MLD) and to explore its clinical significance., Methods: The dynamic change of T FH cells, ICOS + - and PD-1 + T FH cells at pretreatment and different treatment periods was determined by flow cytometry in 85 MLD patients. Concentration of interleukin 21 (IL-21) was evaluated by ELISA, and the correlation between clinical prognosis and the ratio of T FH cells was analyzed., Results: Significantly increased ICOS + - and PD-1 + T FH cells were found in MLD patients at pretreatment compared to healthy controls. Decreased or even close to normal levels of ICOS + - and PD-1 + T FH cells were found at the end of treatment. However, in the patients with progressive disease, high levels of ICOS + - and PD-1 + T FH cells were found. Moreover, a significantly increased plasma IL-21 level was found in MLD patients. Negative correlation was found between the level of ICOS + -, PD-1 + T FH cells, as well as IL-21 and the prognosis of MLD., Conclusions: Significantly increased T FH cell ratios were found in patients with MLD, and decreased T FH cells ratios could be expected in those treatment-effective patients, which could be used as the therapeutic efficacy index.

Data on the risk of lymphatic and hematopoietic neoplasms among workers whose jobs entail high exposure to polycyclic aromatic hydrocarbons (PAH) are sparse, and mainly based on small-size studies. We carried out a systematic review of occupational cohort studies that reported results on incidence or mortality from Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), leukemia or multiple myeloma (MM) among workers exposed to PAH. We computed meta-analytic estimates using a random effect model. Meta-relative risk (meta-RR) was computed separately by each type of neoplasm, job or industry. We identified 41 studies (12 in iron and steel foundries, 11 in aluminum plant, 6 in cokeries, 6 in carbon electrode manufacturing, 2 on asphalt workers, 2 on creosote-exposed workers, 1 on tar distillery workers and 1 evaluating both tar distillery workers and roofers). No significant excess risk of any lymphatic and hematopoietic neoplasms was found among workers employed in jobs or industries entailing high PAH exposure. Among 18 meta-analytic estimates by job or industry and type of neoplasm, 16 were close to unit, i.e., between 0.72 and 1.27, whereas the meta-RR was 1.38 [95 % confidence interval (CI) 0.95-2.01] for HL in foundry workers and 2.01 (95 % CI 0.96-4.22) for NHL in workers exposed to creosote. There was no association between occupation entailing high PAH exposure and risk of MM or leukemia.

Importance: Frailty results in decreased physiological reserve and diminished resistance to stressors; approximately 10% of those in the elderly population (those ≥65 years) are frail. High-intensity treatments and complications after hematopoietic cell transplantation (HCT) injure normal tissues and may increase the risk of frailty even among nongeriatric HCT patients., Objective: To determine the prevalence of frailty in young adult HCT patients (18- to 64-year-olds) and siblings; and the impact of frailty on subsequent mortality in HCT survivors., Design, Setting, and Participants: This cohort study, conducted in August 2015 examined 998 HCT survivors, who underwent transplant procedures between 1974 and 1998, who have survived at least 2 years after HCT, and 297 frequency-matched siblings. The study was performed at City of Hope or University of Minnesota with participants completing surveys at home or in the clinic. Hematopoietic cell transplantation survivors and siblings participating in the Bone Marrow Transplant Survivor Study (BMTSS) completed a frailty survey between February 13, 1999 and June 15, 2005 (median time since HCT: 7.9 years); HCT survivors were followed for subsequent mortality (median: 10.3 years from survey)., Main Outcomes and Measures: Prevalence and predictors of frailty; impact of frailty on subsequent mortality in HCT survivors. Frailty phenotype defined as exhibiting 3 or more of the following characteristics: clinically underweight, exhaustion, low energy expenditure, slow walking speed, and muscle weakness. The national Death Index, Social Security Death Index and medical records were used for mortality assessment as of December 21, 2011., Results: The 998 HCT survivors were a mean (SD) of 42.5 (11.6) years of age, and the 297 matched siblings were 43.8 (10.9) years of age. The prevalence of frailty among young adult HCT patients exceeded 8%. The HCT survivors were 8.4 times more likely to be frail than their siblings (95% CI, 2.0-34.5; P = .003). Among HCT recipients, allogeneic HCT recipients with chronic graft-vs-host disease (GvHD) were at increased risk of frailty compared with autologous HCT (OR,15.02; 95% CI, 6.6-34.3; P < .001); resolved chronic GvHD (OR, 2.7; 95% CI, 1.1-6.9; P = .04). Cumulative incidence of subsequent all-cause mortality was 39.3% and 14.7% at 10 years for HCT recipients with and without frailty, respectively (P < .001). Frailty was associated with a 2.76-fold (95% CI, 1.7-4.4; P < .001) increased risk of subsequent mortality after adjusting for relevant prognosticators., Conclusions and Relevance: The prevalence of frailty among young-adult HCT survivors approaches that seen in the elderly general population. Frail HCT survivors are at increased risk of subsequent mortality when compared with nonfrail survivors. This study identifies vulnerable populations needing close monitoring to anticipate and manage morbidity and prevent mortality., Competing Interests: Disclosures: None reported.

Treatments for patients with hematologic malignancies not in remission are limited, but a few clinical studies have investigated the effects of salvaged unrelated cord blood transplantation (CBT). We retrospectively studied 19 patients with acute leukemia, 5 with myelodysplastic syndrome (MDS with refractory anemia with excess blasts [RAEB]), and 2 with non-Hodgkin's lymphoma who received 1 CBT unit ≤ 2 loci human leukocyte antigen (HLA)-mismatched after undergoing myeloablative conditioning regimens between July 2005 and July 2014. All of them were in non-remission before transplantation. The infused total nucleated cell (TNC) dose was 4.07 (range 2.76-6.02) × 10⁷/kg and that of CD34⁺ stem cells was 2.08 (range 0.99-8.65) × 10⁵/kg. All patients were engrafted with neutrophils that exceeded 0.5 × 10⁹/L on median day +17 (range 14-37 days) and had platelet counts of >20 × 10⁹/L on median day +35 (range 17-70 days). Sixteen patients (61.5%) experienced pre-engraftment syndrome (PES), and six (23.1%) patients progressed to acute graft-versus-host disease (GVHD). The cumulative incidence rates of II-IV acute GVHD and chronic GVHD were 50% and 26.9%, respectively. After a median follow-up of 27 months (range 5-74), 14 patients survived and 3 relapsed. The estimated 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) rates were 50.5%, 40.3%, and 35.2%, respectively. Salvaged CBT might be a promising modality for treating hematologic malignancies, even in patients with a high leukemia burden.

Reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplant (allo-SCT) have used alemtuzumab to abrogate the risk of graft-versus-host disease (GVHD). Thirty-eight patients with advanced lymphoma underwent a prospective phase II study of melphalan, fludarabine and alemtuzumab containing RIC allo-SCT from 20 matched related and 18 unrelated donors with cyclosporine-A as GVHD prophylaxis. The cumulative incidence of grade II-IV acute GVHD at 3 months was 10.5% and three evaluable patients experienced chronic GVHD. Progression-free (PFS) and overall (OS) survival at 5 years was 25% (95% confidence interval [CI]: 13-40%) and 44% (95% CI: 28-59%), respectively. Previous high-dose therapy and autologous stem cell transplant (HDT-ASCT) and elevated lactate dehydrogenase (LDH) at the time of allo-SCT resulted in inferior OS. Within this cohort of patients with high-risk lymphoma, alemtuzumab containing RIC resulted in a low risk of GVHD and a high incidence of progression of disease, especially in those with poor-risk features defined by elevated LDH pre-allo-SCT and previous HDT-ASCT.

Objective: Leukemias comprise the most common group of cancers in children and adolescents. Studies conducted in other countries and Brazil have observed a decrease in their mortality.This study aimed to evaluate the trend of mortality from leukemia in children under 19 years of age in Brazil, from 1980 to 2010., Methods: This was an ecological study, using retrospective time series data from the Mortality Information System, from 1980 to 2010. Calculations of mortality rates were performed, including gross, gender-specific, and age-based. For trend analysis, linear and semi-log regression models were used. The significance level was 5%., Results: Mortality rates for lymphoid and myeloid leukemias presented a growth trend, with the exception of lymphoid leukemia among children under 4 years of age (percentage decrease: 1.21% annually), while in the sub-group "Other types of leukemia", a downward trend was observed. Overall, mortality from leukemia tended to increase for boys and girls, especially in the age groups 10-14 years (annual percentage increase of 1.23% for males and 1.28% for females) and 15-19 years (annual percentage increase of 1.40% for males and 1.62% for females)., Conclusions: The results for leukemia generally corroborate the results of other similar studies. A detailed analysis by subgroup of leukemia, age, and gender revealed no trends shown in other studies, thus indicating special requirements for each variable in the analysis., (Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: To identify disparities-using recursive partitioning (RP)-in early survival for children with leukemias treated in Argentina, and to depict the main characteristics of the most vulnerable groups., Methods: This secondary data analysis evaluated 12-month survival (12-ms) in 3 987 children diagnosed between 2000 and 2008 with lymphoid leukemia (LL) and myeloid leukemia (ML) and registered in Argentina's population-based oncopediatric registry. Prognostic groups based on age at diagnosis, gender, socioeconomic index of the province of residence, and migration to a different province to receive health care were identified using the RP method., Results: Overall 12-ms for LL and ML cases was 83.7% and 59.9% respectively. RP detected major gaps in 12-ms. Among 1-10-year-old LL patients from poorer provinces, 12-ms for those who did and did not migrate was 87.0% and 78.2% respectively. Survival of ML patients < 2 years old from provinces with a low/medium socioeconomic index was 38.9% compared to 62.1% for those in the same age group from richer provinces. For 2-14-year-old ML patients living in poor provinces, patient migration was associated with a 30% increase in 12-ms., Conclusions: Major disparities in leukemia survival among Argentine children were found. Patient migration and socioeconomic index of residence province were associated with survival. The RP method was instrumental in identifying and characterizing vulnerable groups.

In the article data are presented about morbidity by oncogematologic pathology - one of the most meaningful of social-economic problems. In Ukraine annually diagnose the to 8 thousand new cases of haemoblastosis. Indexes of morbidity on a 100 thousand population are 5,2; at illness of Hodgkin's lymphoma - 2,5, at plural myeloma - 1,6; at leukemia - 8,1. Morbidity by haematological pathology in Kyiv long time remains high: annually 250 expose patients with malignant lymphnoma, 57 - with myeloma, 190 - with leukemia, from them at 55 % is a sharp form and at 40 % - chronic. The anxiety of doctors causes circumstance that the special treatment is overcome 58,1 % patients by leukemia, 68,6 % - plural myeloma and 77,8 % patients with malignant lymphoma. World experience shows that application of complex methods of therapy allows to prolong life-span 80-90 % patients with Hodgkin's malignant lymphoma on 10, and at 95 % patients by a lymphogranulomatosis - to attain nonrecurrence survival to 5 years.

Patient readmission within 30 days from discharge has been perceived by the Centers for Medicare and Medical Services as an indicator of poor healthcare quality for specific high-cost medical conditions. Patients who undergo allogeneic hematopoietic cell transplantation (allo-HCT) are often being readmitted. Our study identified the risk factors for 30-day readmission among 618 adult recipients of myeloablative allo-HCT from 1990 to 2009. Two hundred forty-two (39%) of 618 patients (median age = 42 years [range: 18-66]) were readmitted a median of 10 days (range: 1-30) from their hospital discharge. Median duration of readmission was 8 days (range: 0-103). Infections (n = 68), fever with or without identified source of infection (n = 63), gastrointestinal complications (n = 44), graft-versus-host disease (GVHD) (n = 38), and other reasons (n = 29) accounted for 28%, 26%, 18%, 16%, and 12% of readmissions, respectively. During their index admission, patients who were subsequently readmitted had more documented infections (P < .001), higher hematopoietic cell transplantation comorbidity index (HCT-CI) (P < .01), total body irridiation (TBI)-based conditioning (P < .001), unrelated donor (P < .001), and peripheral stem cell (P = .014) transplantation. In multivariable analysis, HCT-CI (odds ratio [OR] = 1.78; 95% confidence interval [CI], 1.25-2.52), TBI-based preparative regimen (OR = 2.63; 95% CI, 1.67-4.13), and infection during admission for allo-HSCT (OR = 2.00; 95% CI, 1.37-2.92) predicted 30-day readmission. Thirty-day readmission itself was an independent predictor of all-cause mortality (hazard ratio [HR](Adj) = 1.66; 95% CI, 1.36-2.10). Our data emphasize the importance of a risk-standardized approach to 30-day hospital readmission if it is used as a quality-of-care metric for bone marrow transplantation., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Basiliximab and daclizumab, two interleukin-2 receptor antagonists (IL-2RAs), prevent graft failure in renal transplantation, which also effectively treat steroid-refractory graft-versus-host disease (GVHD). However, only a few studies report that IL-2RAs prevent GVHD. Here we first retrospectively explored the prophylactic effects of basiliximab or daclizumab against GVHD in 82 patients with hematologic malignancies following unrelated donor-peripheral blood stem cell transplantation (URD-PBSCT). All recipients achieved engraftment. The rates of grade II-IV and III-IV acute GVHD (aGVHD) were 35.4% and 15.9%, respectively. Chronic GVHD (cGVHD) developed in 38.7% of evaluable patients. The transplantation-related mortality was 13.4%, while relapse rate was 8.5%. The 2-year overall survival (OS) reached 77.1% and disease-free survival (DFS) accumulated to 72.2%. The side effects of basiliximab and daclizumab were moderate and tolerable. There were no significant differences in aGVHD onset and survival between the daclizumab and basiliximab groups. However, basiliximab presented superior prophylactic effects on cGVHD than daclizumab. In conclusion, basiliximab or daclizumab prevents GVHD efficiently and feasibly following URD-PBSCT, and contributes to favorable outcome. Basiliximab has a similar effect on aGVHD but superior activity against cGVHD. Further prospective and randomized control studies are needed., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Cancer cells acquire abnormalities in energy metabolism, collectively known as the Warburg effect, affecting substrate availability of thiamine-dependent enzymes. To investigate a strategy to exploit abnormal cancer-associated metabolism related to thiamine, we tested the cytotoxicity of native Bacillus thiaminolyticus thiaminase I enzyme, which digests thiamine, in the NCI60 cell line drug cytotoxicity screening program and found that leukemia cell lines were among the most sensitive to thiaminase I. We obtained additional lymphoid leukemia cell lines and confirmed that native thiaminase I and linear chain PEGylated thiaminase I enzyme (LCPTE) have cytotoxic activity in these cell lines. In addition, the IC(50) of 3 of the 5 leukemia cell lines (Reh, RS4, and Jurkat) were at least 1,000-fold more sensitive than Molt-4 cells, which in turn, were among the most sensitive in the NCI60 panel. The 3 LCPTE-sensitive leukemia cell lines were also sensitive to removal of thiamine from the medium, thus suggesting the mechanism of action of LCPTE involves extracellular thiamine starvation. Surprisingly, rapamycin showed a protective effect against LCPTE toxicity in the 3 LCPTE-sensitive cell lines but not in the other 2 cell lines, suggesting involvement of an mTOR-dependent pathway. Immunoblot analysis of the LCPTE-sensitive cell lines after LCPTE exposure revealed changes in mTOR pathway phosphorylation. Nude mice bearing RS4 leukemia xenografts showed both tumor growth delay and prolonged survival after a single dose of LCPTE. Therefore, disruption of thiamine-dependent metabolism may be a novel therapeutic approach to target altered energy metabolism in leukemia and other cancers.

The authors used cancer registry data to assess the incidence rate of second primary cancers among chronic myeloid leukemia (CML) patients and the long-term survival of CML patients before the introduction of tyrosine kinase inhibitors. In the Swedish Cancer Registry, the authors identified 2,753 adult CML patients diagnosed between 1970 and 1995 who were followed through December 2007. Standardized incidence ratios (SIRs) and relative survival ratios were computed. With a total of 145 subsequent primary malignancies, an increased incidence rate of second malignancy was found for stomach cancer (SIR = 2.76, 95% confidence interval (CI): 1.33, 5.08), skin cancer (SIR = 5.36, 95% CI: 3.18, 8.47), urogenital tract cancer (SIR = 1.61, 95% CI: 1.15, 2.21), and lymphoid leukemia (SIR = 5.53, 95% CI: 1.79, 12.89). Long-term relative survival figures showed that CML was related, in the era prior to the introduction of imatinib, to a very steep decline in survival (2 years from diagnosis, relative survival = 51%, 95% CI: 49, 53). This was in spite of a marginal improvement after 1985, possibly related to the introduction of interferon-α for treatment. These estimates constitute a relevant reference for future studies and a benchmark for comparisons with prognosis in CML patients after chronic use of tyrosine kinase inhibitors.

Purpose: This study explores the experiences of individuals in early, middle, and late adolescence dying from cancer. Place of death, medications used at end of life (EOL), and discussions prior to death are examined., Methods: Data were obtained from a retrospective review of medical charts from 103 adolescents who died of cancer between 2000 and 2005., Results: Adolescents with leukemia/lymphoma were relatively more likely to die in an intensive care unit (p = 0.028) where cause of death was more likely to be treatment-related (p < 0.001), and EOL discussions more likely to occur in the last 7 days of life (p = 0.002). Anxiolytic use was significantly higher during late adolescence (p = 0.037)., Conclusions: Adolescents have unique developmental needs that should be considered at EOL. Timing of EOL discussions occurred very close to death for a significant number of adolescents, allowing very little time to psychologically prepare for death.

Background and Objective: Cancer is one of the most primary causes of death for children. The study was to analyze the cancer incidence and mortality of children in urban districts of Guangzhou between 2000 and 2004, to explore the incidence regularity of pediatric cancers and to provide a reference for prevention and treatment of pediatric cancers., Methods: The data of cancer incidence and mortality of children during 2000-2004 were collected from Guangzhou Population-based Cancer Registry, and were calculated and analyzed., Results: The cancer incidence of children between 2000 and 2004 in Guangzhou was 17.91 per 100,000 (18.92 per 100,000 in males, 16.70 per 100,000 in females); the cancer mortality was 4.73 per 100,000 (4.65 per 100,000 in males, 4.83 per 100,000 in females). The incidence of lymphoid leukemia ranked first followed by cancer of central nervous system and non-Hodgkin's lymphoma. Cancer incidence was 77.52 per 100 000 in children of less than one year old, 21.49 per 100,000 in 1-4 years, 9.66 per 100,000 in 5-9 years and 17.11 per 100 000 in 10-14 years, with significant difference among the four groups (Chi(2) = 307.602, P < 0.001)., Conclusion: Lymphoid leukemia, cancer of central nervous system and non-Hodgkin's lymphoma are the most common cancers in children. The children of 0-4 years old are the population with high cancer incidence.

Soluble CD83 (sCD83), a potent immunosuppressive agent, circulates at elevated levels in some chronic lymphocytic leukemia (CLL) patients. We report that CLL patients with elevated plasma sCD83 levels had significantly shorter (P=0.038) treatment free survival. Culture of CLL cells with solid phase CD83 mAb+IL-4 significantly increases sCD83 release (23-117-fold, P=0.013) and ligation of normal donor PBMC with solid phase CD83 mAb alone induces similar significant increases in sCD83 release (P=0.003). RT-PCR analysis detected the presence of a transcript for sCD83 in 2/3 CLL samples. These results suggest sCD83 release may play a regulatory role in CLL progression.

This paper considers the problem of obtaining a dynamic prediction for 5-year failure free survival after bone marrow transplantation in ALL patients using data from the EBMT, the European Group for Blood and Marrow Transplantation. The paper compares the new landmark methodology as developed by the first author and the established multi-state modeling as described in a recent Tutorial in Biostatistics in Statistics in Medicine by the second author and colleagues. As expected the two approaches give similar results. The landmark methodology does not need complex modeling and leads to easy prediction rules. On the other hand, it does not give the insight in the biological processes as obtained for the multi-state model.

Background: Little is known about the effect of migrant status on childhood cancer survival. We studied cancer survival among children of Turkish descent in the German Cancer Childhood Registry, one of the largest childhood cancer registries worldwide., Methods: We identified children of Turkish descent among cancer cases using a name-based approach. We compared 5-year survival probabilities of Turkish and other children in three time periods of diagnosis (1980-87, 1988-95, 1996-2005) using the Kaplan-Meier method and log-rank tests., Results: The 5-year survival probability for all cancers among 1774 cases of Turkish descent (4.76% of all 37.259 cases) was 76.9% compared to 77.6% in the comparison group (all other cases; p = 0.15). We found no age- or sex-specific survival differences (p-values between p = 0.18 and p = 0.90). For the period 1980-87, the 5-year survival probability among Turkish children with lymphoid leukaemia was significantly lower (62% versus 75.8%; p < 0.0001), this remains unexplained. For more recently diagnosed leukaemias, we saw no survival differences for Turkish and non-Turkish children., Conclusion: Our results suggest that nowadays Turkish migrant status has no bearing on the outcome of childhood cancer therapies in Germany. The inclusion of currently more than 95% of all childhood cancer cases in standardised treatment protocols is likely to contribute to this finding.

The Class II human leukocyte antigen (HLA) DRB1 antigen DR4 is associated with autoimmune disorders and response to cyclosporine immunosuppression in T-lymphoproliferative disorders. We retrospectively reviewed the role of HLA DR4 on outcomes in 77 related and 22 unrelated consecutive first HLA-matched alloHSCT patients with lymphoid malignancies treated between 1992 and 2003. HLA DRB1 typing was determined by molecular (n = 69) or serologic (n = 30) methods. The proportion of patients with one HLA DR4 antigen was 18% (18/99). At a median follow-up of 5.6 years, there were no significant differences in aGvHD, cGvHD and OS between the HLA DR4 positive versus negative patients in any disease or donor subgroups. Nine of 18 (50%) DR4 positive patients and 20 of 81 (25%) DR4 negative patients had disease progression post HSCT (p = 0.033). Progression-free survival (PFS) at 3 years was 29% in the DR4 positive group and 70% in the DR4 negative group (p = 0.004). In univariate and multivariate analyses, DR4 positivity was the only significant factor associated with PFS (RR = 3.2, p = 0.007). Our results suggest that in addition to the known role of HLA DRB1 disparity in mediating histocompatibility, HLA DR4 is associated with inferior PFS in patients with lymphoid malignancy undergoing alloHSCT.

Purpose: The HOX genes comprise a large family of homeodomain-containing transcription factors, present in four separate clusters, which are key regulators of embryonic development, hematopoietic differentiation, and leukemogenesis. We aimed to study the role of DNA methylation as an inducer of HOX gene silencing in leukemia., Experimental Design: Three hundred and seventy-eight samples of myeloid and lymphoid leukemia were quantitatively analyzed (by COBRA analysis and pyrosequencing of bisulfite-modified DNA) for methylation of eight HOXA and HOXB cluster genes. The biological significance of the methylation identified was studied by expression analysis and through re-expression of HOXA5 in a chronic myeloid leukemia (CML) blast crisis cell line model., Results: Here, we identify frequent hypermethylation and gene inactivation of HOXA and HOXB cluster genes in leukemia. In particular, hypermethylation of HOXA4 and HOXA5 was frequently observed (26-79%) in all types of leukemias studied. HOXA6 hypermethylation was predominantly restricted to lymphoid malignancies, whereas hypermethylation of other HOXA and HOXB genes was only observed in childhood leukemia. HOX gene methylation exhibited clear correlations with important clinical variables, most notably in CML, in which hypermethylation of both HOXA5 (P = 0.00002) and HOXA4 (P = 0.006) was strongly correlated with progression to blast crisis. Furthermore, re-expression of HOXA5 in CML blast crisis cells resulted in the induction of markers of granulocytic differentiation., Conclusion: We propose that in addition to the oncogenic role of some HOX family members, other HOX genes are frequent targets for gene inactivation and normally play suppressor roles in leukemia development.

The dose-response assessment of the association between 1,3-butadiene (BD) and leukemia mortality among workers in the North American synthetic rubber industry is explored. Analyses are based on the most recent University of Alabama at Birmingham epidemiological study and exposure estimation. The U.S. EPA Science Advisory Board recommendations of using the most recent data and giving consideration to peak exposures to BD have been followed. If cumulative BD ppm-years is to be used as the predictor of the leukemia rate ratio, then the performance of that predictor is statistically significantly improved if the slope in the predictor is estimated with age and the cumulative number of BD peaks (where a BD peak is any exposure, regardless of duration, to a BD concentration above 100 ppm) added as categorical covariates. After age and the cumulative number of BD peaks are incorporated as categorical covariates in the Poisson regression model, the estimated concentration (EC(001)) corresponding to an excess risk of 0.001 as a result of continuous environmental exposure is 11.2 ppm; however, the estimated slope for BD cumulative ppm-years in the linear rate ratio for leukemia used to derive this EC(001) is not statistically significantly different from zero. Sensitivity analyses using alternative models indicate either essentially no risk or estimated EC(001) values of 9 and 77 ppm. Analyses suggesting the absence of a statistically significant low-dose risk versus cumulative BD ppm-years are presented. Sensitivity analyses of other malignant neoplasms of lymphatic and hematopoietic tissue (specifically, lymphoid and myeloid neoplasms) resulted in conclusions about the dose-response modeling methodology that were supportive of the methodology used for leukemia.

Purpose: To characterize the clinical and imaging features of orbital leukemic tumors in 27 patients seen and treated at St. Jude Children's Research Hospital., Methods: A retrospective review was performed on the clinical and imaging records of 27 consecutive patients with a diagnosis of orbital leukemic tumors. The following data were extracted from the patients' records: age at diagnosis of orbital leukemic tumors, sex, race, national origin, type of leukemia, temporal relationship of orbital disease to diagnosis of leukemia, survival from diagnosis of orbital leukemic tumor, laterality of the orbital disease, location of the mass within the orbit, imaging features of the mass, chemotherapeutic protocol, treatment with bone marrow transplant, and orbital radiation., Results: The median age at diagnosis of orbital leukemic tumor was 8 years (range, 1-18 years). Nineteen of the 27 patients were male, and 21 patients were born and lived in the United States. Twenty-one patients had acute myeloid leukemia, five had acute lymphoblastic leukemia, and one had chronic myelogenous leukemia. In 85% of patients (n = 23), the diagnosis of leukemia was based on the bone marrow examination findings. Orbital imaging revealed homogenous masses that molded to one or more orbital walls without bony destruction. Nine patients had bilateral orbital involvement. All patients received multiagent systemic chemotherapy, and 14 underwent bone marrow transplantation. Five patients received external beam radiation for the treatment of orbital disease. Fifteen (55.6%) of the 27 patients were alive at the time of the study. The median survival for all patients was 4.75 years (range, 0.1-24 years) after the diagnosis of orbital disease., Conclusions: Orbital leukemic tumors occur most commonly in the first decade of life, in association with acute myeloid leukemia. They appear as homogenous masses along the orbital walls. Although the overall survival rate for patients with leukemia has improved over the past 3 decades, the mortality of patients who develop orbital leukemic tumors remains high.

CBV and BEAM are the two most frequently used regimens for patients with lymphoma undergoing autologous hematopoietic stem-cell transplantation (ASCT). This study compared their morbidity and transplant-related mortality (TRM) in 113 patients with non-Hodgkin's lymphoma (69) and Hodgkin's disease (44) undergoing ASCT between 1990 - 2004. CBV (cyclophosphamide, 6000 mg m(-2); VP-16, 750 mg m(-2); and high-dose BCNU, 800 mg m(-2)) was administered to 75 patients and 38 received BEAM (BCNU, 300 mg m(-2); VP-16, 800 mg m(-2); cytarabine, 800 mg m(-2); melphalan, 140 mg m(-2)). Patients in the BEAM group had a significantly higher median age (p = 0.002) and were more heavily treated before ASCT (p = 0.003). More patients showed active disease at transplant in the BEAM group (p = 0.04). Sinusoidal obstruction syndrome (SOS) was more frequent in the CBV group (11% vs 0%, p = 0.048). There were 20 (18%) transplant-related deaths, 18 in the CBV and two in the BEAM group. Infectious complications (12 patients, seven with pneumonia) and SOS (four) were the most frequent causes of death. The cumulative incidences of TRM were 25% in the CBV and 7% in the BEAM group (p = 0.02). CBV thus produced a higher incidence of SOS and TRM than BEAM in this series.

Diffuse large B-cell lymphoma (DLBCL) in adults is a heterogeneous disease. Biologic subgroups of DLBCL with a favorable prognosis (germinal center B-cell-like, GCB) and with a poor prognosis (activated B-cell-like, ABC) have been defined by gene expression profiling and can be distinguished by immunohistochemistry. In contrast to their adult counterparts, children with DLBCL have an excellent prognosis. We analyzed 63 cases of DLBCL in pediatric patients by immunohistochemistry and fluorescence in situ hybridization (FISH) and found a striking predominance of a GCB subtype, which might explain the good clinical outcome in these lymphomas. Interestingly, FISH applied to 50 of these cases, as well as conventional cytogenetics available in 3 cases, revealed absence of the translocation t(14;18) involving the BCL2 gene, which is present in about 15% of adult GCB subtype DLBCL. Our data indicate that pediatric DLBCL differs from adult DLBCL and might comprise a biologically unique subgroup of DLBCL from which important insights into the pathogenesis and biology of this disease might be gained.

Background: Blastic natural killer (NK) cell lymphoma/leukemia (BNKL) is an immature CD56-positive neoplasm, which was recognized recently and characterized by systemic proliferation of tumor cells including skin, lymph node, and bone marrow., Methods: The current study analyzed 47 patients with BNKL (27 had leukemias and 20 had lymphomas). Patient data were collected for the survey of the NK-Cell Tumor Study Group., Results: There were 33 males and 14 females, with a median age of 53 years (range, 3 months to 89 years). There were few clinicopathologic differences between the leukemia and lymphoma types. Cutaneous involvement was noted at diagnosis in 28 patients, who presented a tendency for older age of onset (median: 56 vs. 46 years, P = 0.11) than patients with noncutaneous BNKL. Cutaneous BNKL showed less frequent mediastinal involvement (4% vs. 53%, P = 0.0002) and less severe thrombocytopenia (P =0 .03). Phenotypic characteristics were also different, with cutaneous BNKL favoring CD4 and HLA-DR expression, and noncutaneous BNKL favoring CD16 and CD34 expression. Both groups responded well to chemotherapy for lymphoid malignancies, but disease recurrence was frequent. The prognosis of patients with noncutaneous BNKL was significantly poorer than that of patients with cutaneous BNKL (median survival: 15 vs. 25 months, P = 0.02). Multivariate analysis confirmed that cutaneous involvement was a significant and independent prognostic factor for BNKL, as were age of onset and leukocyte count., Conclusions: These findings suggested that BNKL is a heterogeneous disease and contains at least two subtypes. Although further investigations are needed to settle a marker for distinction, the presence of cutaneous involvement is a useful prognostic factor.

Over a 3-year period, 145 patients ineligible for myeloablative conditioning underwent reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (SCT) from an HLA-identical sibling in a prospective study. The median age was 54 years, 88 patients were male and 61 patients were beyond the early-intermediate phase of their disease. The 100-day probability of developing grade II-IV acute graft-versus-host disease (GVHD) was 34%, and the 1-year probability of developing chronic extensive GVHD was 41%. The 1-year probabilities of transplant-related mortality (TRM), overall (OS) and progression-free survival were 20, 60 and 52%, respectively. Multivariate analyses found a better OS in: (i) patients <60 years; and (ii) recipients of a first SCT; and a higher TRM in: (i) age >60 years, (ii) recipients of a prior autologous SCT, and (iii) an ECOG performance status >1. The 1-year TRM in patients with 0 or 1 and >2 of the above-mentioned adverse prognostic factors were 17 vs 53%, respectively (P<0.001). In summary, our study shows that elderly patients have a higher TRM following an RIC protocol. However, age by itself should not preclude these RIC transplants, since TRM appears to be unacceptably high only in the presence of additional adverse factors.

Although acute myeloid and lymphoid leukemia initially respond to conventional chemotherapy, most patients relapse and succumb from their disease. For the past 30 years, efforts at intensifying induction or postremission conventional chemotherapy have met with limited success. Of all the therapies examined, allogeneic hematopoietic stem cell transplantation has achieved the best outcomes, with the first reports of cure 25 years ago. Most phase III studies have failed to demonstrate a clear advantage of allografting over chemotherapy because of significant risk of transplant-related mortality. However, there is reason for optimism based on the identification of high-risk groups and from improvements in the prevention and management of transplant-related complications. These accomplishments, along with a recent increase in the donor pool through the availability of unrelated donors and cryopreserved umbilical cord blood stem cells, continue to make allografting the most promising curative modality for acute leukemias.

Psychological factors may be associated with the outcome of cancer treatment, including bone marrow transplantation (BMT). However, studies on the issue have provided controversial results. In the present study, effects of mood status on the outcome was studied through a follow-up period of 1-3 years as well as in shorter periods (3 and 8 months) post-BMT in 72 Japanese patients with leukemia. Psychological status was evaluated 2 weeks before BMT using Profile of Mood States (POMS). The most major factor abstracted from the POMS subscales (Factor 1, mainly comprising anxiety, depression, anger, fatigue and confusion) was associated with disease-free survival rate at 3 months post-BMT. However, the factor most significantly associated with the outcome was gender. Females had better outcome than males through the period of 1-3 years as well as at 8 months post-BMT. When analyzed by gender, Factor 1 was associated with poor prognosis at 3 and 8 months in males. In females, however, Factor 1 was not significantly associated with the prognosis. The present results suggest an association between mood status pre-BMT and prognosis post-BMT in a gender-specific manner.

Objective: To analyze the spatial distribution of mortality by leukemia in the population, looking for clusters, and to establish an association with the level of industrialization., Method: The study was carried out in 43 state regions of the state of São Paulo, Brazil, in the period between 1991 and 1995. It was created an Index of Industrialization-Related Leukemia (IIRL) based on number of manufactures and industrial jobs per 100,000 inhabitants, fiscal aggregated value, diversity of industry activities and presence of manufactures that poses potential risk exposure for leukemia. IIRL was classified in five categories. Standardized leukemia mortality rates were established for each region, classified in five categories, plotted in five different colors and compared to the IIRL map., Results: The most industrialized regions in the state of São Paulo are Campinas, Piracicaba, Jundiaí, Sorocaba and São Paulo. There was no relationship between mortality by any leukemia type and industrialization. The region of Jales showed the highest standardized mortality rates by leukemia., Conclusions: Mortality by leukemia had a homogeneous distribution in the state of São Paulo and no association with the level of industrialization. However, aspects related to the epidemiological method applied--ecological study, mortality by leukemia as a parameter to study a disease which prognosis has changed in the last decades--limit the results interpretation.

Among all specific environmental pollution the chemical compounds released in the oil refine process seem to hold the biggest interest. At Medical University of Warsaw we have been studying the influence of the Płock petroleum refinery plant pollution to citizens' health status for over 30 years. The high amount of hydrocarbons--including benzene--were presented in emission. One of the study objectives was to analyze death causes in Płock and Kutno and in the Płock area--according to environmental criteria. The population of the non-petrochemic polluted city Kutno was chosen as the control group. The previous analysis in 1984-1993 showed increased lymphatic or erythrocyte line leukaemia mortality in Płock population vs Kutno population. Similar situation was observed between the area of increased environmental petrochemical pollution and non-polluted area. In this article the Potential Years of Life Lost ratio was used to estimate the life deficiency as the measure of health needs due to mentioned neoplasms. Data indicate that the health needs are bigger than the mortality analysis has shown.

Background and Purpose: To evaluate the efficacy and toxicity of a highly immuno- and myelo-suppressive conditioning regimen followed by the infusion of large numbers of T-cell-depleted mismatched haematopoietic stem cells in 43 high-risk acute leukaemia patients., Results: A high rate of engraftment (95%) and no graft-versus-host disease (GvHD) were observed. The 4-year probability of event-free survival was 0.25+/-0.09 for acute myeloid leukaemia and 0.17+/-0.07 for acute lymphoid leukaemia patients., Conclusions: This study shows that the main obstacles limiting the use of mismatched transplants, i.e. GvHD and rejection, were overcome.

Cytomegalovirus (CMV) pneumonia is reportedly unusual among adults with leukemia who have not undergone transplantation. To assess the frequency of CMV pneumonia and its outcome during the present time, we reviewed the experience of 2136 hospitalized adults with leukemia. Sixty-one patients (2.9%) had CMV pneumonia diagnosed. The frequency doubled from 1.4% in 1992--1994 to 2.8% in 1995--1997 (P<.05). Fifty-four patients (89%) had received treatment with an immunosuppressive chemotherapeutic regimen that contained fludarabine (n=37), high-dose cytoxan (n=17), or both (n=10), and 15 patients (25%) had received granulocyte transfusions that were stimulated with hematopoietic growth factors from unscreened donors. The overall CMV pneumonia--associated mortality rate was 57%. Among autopsied patients who had leukemia, the frequency of CMV pneumonia increased from 0%, 2.3%, and 0% in 1992, 1993, and 1994, respectively, to 4.6%, 6.5%, and 16% in 1995, 1996, and 1997, respectively (P<.05). CMV has emerged as an important cause of life-threatening pneumonia in adults with leukemia who have received potent immunosuppressive therapies and stimulated granulocyte transfusions from unscreened donors.

Monoclonal antibodies have become an important modality for cancer therapy. Genetically engineered chimeric and humanized antibodies have demonstrated activity against both overt leukemia and minimal residual disease. High-dose radioimmunotherapy can potentially allow intensification of antileukemic therapy before bone marrow transplantation yet minimize radiation exposure to normal organs. Targeted alpha particle therapy offers the possibility of selective tumor cell kill while sparing surrounding normal cells. Antibody-drug conjugates and immunotoxins have produced complete remissions in leukemia.

Classification of lymphoid malignancy has changed markedly in recent years and advances have been made in therapy. This study investigated the variations in treatment and survival of 1622 patients in a population-based registry. A total of 1009 cases of malignant lymphoma (ML) were classified according to the Kiel classification. Pathology review resulted in major diagnostic changes for 24% of cases. Of the ML cases, 39% had not had full staging procedures. Younger patients were more likely to have been treated with multiagent chemotherapy regimens, as were patients with B symptoms. Median survival for ML patients was 12 months for high-grade patients and more than 60 months for low-grade patients. Significant factors affecting the survival of ML patients were performance status, whether treatment had followed a recognised protocol, whether treatment had been carried out at a specialist oncology centre (SOC), grade of disease, stage, gender and age. The same factors had a significant effect on survival of the leukaemia patients, except for treatment at an SOC, which had a significant favourable effect on survival of acute lymphoblastic leukaemia (ALL) patients only. Median survival for patients with chronic lymphocytic leukaemia was 43 months and 7 months for ALL patients.

A total of 219 families of patients with cystic fibrosis living in Wales were studied for the occurrence of other diseases and for cause of death, and the findings in relation to leukaemia are reported. There were eight deaths due to leukaemia, five of the myeloid type, in first and second degree relatives; this is significantly more than the expected on the basis of national age specific mortality rates. In comparison, mortality among siblings, parents, aunts and uncles, and grandparents from all causes was within the expected. Screening the five patients with myeloid leukaemia for the delta F508 mutation showed that four were carriers of this mutation. It is concluded that carriers of the delta F508 mutation may have an increased risk of developing acute myeloid leukaemia. This could happen through the direct effect of the cystic fibrosis gene itself, or through its influence on another gene, such as the met oncogene, or gene(s) involved in granulocyte function on the long arm of chromosome 7.

Thirty-six successive adult patients with lymphoblastic lymphoma entered a study of sequential chemotherapy consisting of an intensive LSA2-L2-type protocol to induce first complete remission. Eighteen patients in first CR (median age 22 years, range 15-51), underwent autologous bone marrow transplantation after receiving a conditioning regimen consisting of cyclophosphamide and total body irradiation. Of these 18 patients, 2 were in stage III and 16 in stage IV; 15 showed mediastinal and 9 bone marrow involvement at diagnosis. The transplant procedure was well tolerated and no treatment-induced deaths occurred. At this time, 14 out of 18 patients are alive and well between 1 and 60 months post transplant (median follow-up time 46 months) with an actuarial disease-free survival of 74%. This phase II study suggests that high-dose chemo-radiotherapy followed by autologous bone marrow transplantation may improve long-term disease-free survival in advanced stage adult lymphoblastic lymphoma.

The authors have analysed the mortality of malignant haemopathies in Yugoslavia from 1978 to 1987. The standardized rate of mortality among all malignant haemopathies was from 6.5 to 7.2%000. These rates were higher in males (7.8-8.8%000), than in the females (4.8-5.9%000). The mortality of this group of malignant tumors shows a decreasing tendency, which is more evident in females than in males. Since Hodgkin's disease and lymphoid leukemia participate with about 50% in the structure of mortality from all malignant hemopathies, and for that reason, mortality from these two diseases is especially analysed. The standardized rate of mortality from Hodgkin's disease was between 1.7-2.5%000 (males 2.1-3.2%000; females 1.3-2.0%000). Mortality from this malignant haemopathy has a tendency of decreasing, which is approximately of the same intensity in both sexes. Mortality from lymphoid leukemia in the period between 1978 and 1987 was from 0.7 to 1.2%000 (males 0.9-1.7%000; females 0.5-1.0%000). The mortality trend from lymphoid leukemia shows a similar slight decrease in males and females.

Dose and dose intensity are believed critical for attaining a maximal therapeutic effect in drug-responsive tumor systems. Childhood acute lymphoblastic leukemia may be an example of such a drug-responsive system as it is cured with current chemotherapy in a majority of cases. Between August 1981 and May 1983, the Childrens Cancer Study Group enrolled 209 children with ALL and unfavorable presenting features in CCG-193P, a trial based on the Berlin Frankfurt Munster 76/79 regimen. The cumulative delivered dose of each medication was recorded prospectively. Patients who completed the intensive portion of therapy in continuous complete remission were ranked by the percentage of protocol required drug delivered from the initiation of therapy to that date. No association was found between delivery of any single drug and subsequent disease-free survival. However, when patients were ranked by the sum of the percentages of protocol vincristine, l-asparaginase, and anthracycline delivered, children in the approximate middle and lower tertiles were 3 and 5 times more likely to have had a subsequent relapse than were those in the upper tertile (P = 0.025, test for trend). Delivery of the full protocol prescribed dose of these agents may have been critical, but corroboration is certainly needed. Only prospective trials can determine if children with acute lymphoblastic leukemia and unfavorable presenting features might benefit from greater use of vincristine, l-asparaginase, and/or anthracycline.

This paper analyzes the clinicopathological features of 31 consecutive adult patients with lymphoblastic lymphoma (LBL) and reports on our experience in treating them with two successive multidrug programs analogous to those used in acute lymphoblastic leukemia (ALL) in adults. Protocol 1 (18 patients) consisted of an intensive four-drug induction therapy (daunorubicin, cyclophosphamide, vincristine, prednisone), CNS prophylaxis (cranial irradiation and intrathecal methotrexate), and continuous maintenance with methotrexate and mercaptopurine for three years, with periodical reinductions with vincristine and prednisone. Protocol 2 (13 patients) included a similar induction regimen (doxorubicin instead of daunorubicin, dexamethasone instead of prednisone), followed by post-remission intensification with alternating courses of non-cross-resistant agents (amsacrine and high dose cytarabine; vincristine, cyclophosphamide and doxorubicin; etoposide and conventional dose cytarabine) given in a cyclical eight-month program. CNS prophylaxis consisted of intrathecal methotrexate and systemic high-dose cytarabine. The patient characteristics of the two therapy groups were comparable. The complete remission (CR) rate for both groups was 77%, with a median overall and relapse-free survival of 18 and 29 months, respectively. The three-year overall survival of complete remitters was 59%. No correlation was found between CR rate and age, mediastinal, or bone marrow involvement. Stage I disease had a significantly higher CR rate (100%) than did stages II-IV (64%). Leukemic evolution occurred in 32% of cases, within a median time of 11 months from diagnosis; meningeal disease developed in six cases (19%); in four of them leukemia was concomitant. No significant differences were found between the two successive treatments for CR rate, survival, CNS relapses or toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Review of 5406 children with acute lymphoblastic (ALL) or nonlymphoblastic leukemia (ANLL) registered with Childrens Cancer Study Group (CCSG) since 1972 identified 115 patients (2.1%) with Down syndrome. The proportion of patients with Down syndrome was the same for ALL (2.1%) and ANLL (2.1%). Patients with ALL with and without Down syndrome did not differ significantly with respect to age at diagnosis, sex, race, morphology (FAB classification), cell surface markers, initial white blood cell count, pretreatment hemoglobin value, hepatomegaly, lymphadenopathy, presence of mediastinal mass, CNS disease at diagnosis, or prognostic group as defined by age and initial white blood cell count. Patients with ALL-Down syndrome less frequently had splenomegaly, had lower pretreatment platelet counts, and more often had normal or elevated IgG or IgA levels. In addition, they had a significantly lower rate of remission (81% versus 94%), a higher mortality during induction therapy (14% versus 3%), and a poorer overall survival with 5-year life table rates of 50% versus 65% (P less than 0.001). If an initial remission was achieved, there were no significant differences with respect to remission duration, survival, or disease-free survival. Patients with ANLL-Down syndrome were younger at diagnosis than those without Down syndrome. There was no significant difference in the remission rates between these patients. Analysis of findings in patients with ANLL provided results similar to those obtained for patients with ALL with regard to clinical outcome after achievement of an initial remission.

It is concluded from the prognostic factors of acute lymphoblastic leukaemia, as far as they have become known up to now, such as initial leukocyte count, extent of organ infiltration, etc, that the pre-diagnostic duration of signs, representing a measure of the proliferation activity of the leukaemia cells, could also represent a relevant prognostic characteristic. A check conducted in 90 children treated between 1966--1975 yields a correlation only between a very short pre-diagnostic duration of signs (less than 2 weeks) and the duration of the first complete remission (as well as the survival time). However, even those prognostic factors which are already generally recognised, possess merely limited reliability, because they do not take the individual response to therapy into account. Hence, improvement of prognosis of the course of the disease can be expected only if the continuous decrease of the remaining population of blasts during the early phase of remission can be determined with greater accuracy than before.

E-rosetting of leukaemic blast cells is one of the markers of T-cell acute lymphoblastic leukaemia (ALL). In children, E+ ALL has a bad prognosis. In adults, data are scarce. This report provides information on 25 E+ ALL adult patients who have a minimum follow-up time of 36 months. Twenty-two of 25 patients (88%) achieved complete remission (CR) (median duration 16 months), and six of them were alive, relapse-free, and off therapy after 36-81 months, with a 26% projected 6-year relapse-free survival. In 97 patients with E-SmIg- ALL, who were treated at the same Institutions, over the same period of time, and by the same modalities, the outcome of therapy was almost identical: CR 80%, median duration of first CR 15 months, projected 6-year relapse-free survival 15%. The white blood cell (WBC) count at presentation influenced significantly and to the same degree first CR length in both E+ and E- cases. In this adult series, WBC count was not as high as in children. Moreover, a high Hb concentration, a very high WBC count, lymphadenomegaly, and mediastinal involvement, were found more frequently in adolescents and young adults than in adults. Based on these data, it is suggested that in adults E-rosetting as such is not a marker of a poorer prognosis, that some of the typical features of children E+ ALL weaken with age, and that in adults the disease can have a less aggressive character.