(90)YIT is well tolerated and achieves high response rates. Patients with increased LDH tend to relapse earlier, and individuals in remission 1 year after (90)YIT appear to have long- lasting responses.

SummaryThe management of patients with Hodgkin lymphoma (HL) recurring after stem cell transplantation (SCT) and multiply relapsed disease remains challenging. We report on 41 such patients who received bendamustine hydrochloride, a bifunctional mechlorethamine derivative mechanistically unrelated to traditional alkylators, after a median of four prior chemotherapy lines, including SCT in 85% of cases. Bendamustine was given at doses of 90-120 mg/m 2 every 21 or 28 d. At first assessment (2-4 cycles), the overall response rate (ORR) was 78% with 12 (29%) complete (CR) and 20 (49%) partial responses (PR). Upon treatment prolongation to 6-8 courses, 40% of PRs progressed, yielding a final ORR of 58% with 31% of CRs. Eight patients (two CRs, six PRs) were subsequently allotransplanted. Median progression-free and overall survival exceeded 11 and 21 months respectively; complete responders displayed a median disease-free survival above 9 months with a relapse rate of only 30%. Outcomes were independent of disease chemosensitivity, previous transplant and bendamustine dose-intensity. No life-threatening or unexpected adverse events occurred.Within the limits of a retrospective analysis and schedule heterogeneity, these results appear very encouraging and prompt prospective trials to confirm bendamustine as a valuable option in the palliative setting and in cytoreductive strategies before allotransplantation.

Summary Specific trials on adult Burkitt lymphoma (BL) and ‘unclassifiable’ lymphomas with features intermediate between BL and diffuse large B‐cell lymphoma (BL/DLBCL) are advocated which include substantial numbers of older patients, to improve treatment feasibility, while countering risks of systemic and central nervous system (CNS) recurrences. We prospectively evaluated a modified CODOX‐M/IVAC (CODOX‐M: cyclophosphamide, vincristine, doxorubicin, high‐dose methotrexate; IVAC: ifosfamide, etoposide and high‐dose cytarabine) regimen by the addition of rituximab (R) and liposome‐encapsulated cytarabine (D) to increase antitumour activity and halve the number of intrathecal treatments. Thirty adults (40% >60 years) with BL (n = 15) and BL/DLBCL (n = 15) were accrued. Primary endpoints were progression‐free survival (PFS), CNS recurrence, and liposomal cytarabine‐associated toxicity. Eighty percent of patients received the whole treatment programme, the remaining cases received at least three full courses. Application of the RD‐CODOX‐M/IVAC regimen resulted in remarkable 4‐year PFS (78%) and complete remission (CR) rates (93%). However, PFS was significantly lower in patients older than 60 years as compared to younger ones (49%vs 93%, P = 0·03; median, 36 months), despite high actual dose‐intensity, CR rate and tolerability. Reduced‐intensity intratechal prophylaxis through liposomal cytarabine was effective because the CNS failure rate was low (3·4%) and without severe neurological toxicities. The RD‐CODOX‐M/IVAC strategy is feasible and highly effective, but improving outcomes in elderly patients remains a priority.

Both regimes showed good tolerability and appealing response rates. FFS was more prolonged in R-GEMOX, but patients continuously relapsed without a clear plateau on survival curves.

This Phase II study assessed feasibility and efficacy of a biweekly R-COMP-14 regimen (rituximab, cyclophosphamide, non-pegylated liposome-encapsulated doxorubicin, vincristine and prednisone) in untreated elderly patients with poor-risk diffuse large B-cell lymphoma (DLBCL) and moderate to high ‘life threat’ impact NIA/NCI cardiac comorbidity. A total of 208 courses were delivered, with close cardiac monitoring, to 41 patients (median age: 73 years, range: 62–82; 37% >75 years) at a median interval of 15·6 (range, 13–29) days; 67% completed all six scheduled courses. Response rate was 73%, with 68% complete responses (CR); 4-year disease-free survival (DFS) and time to treatment failure (TTF) were 72% and 49%, respectively. Failures were due to early death (n = 3), therapy discontinuations (no-response n = 2; toxicity n = 6), relapse (n = 6) and death in CR (n = 3). Incidence of cardiac grade 3–5 adverse events was 7/41 (17%; 95% confidence interval: 8–31%). Time to progression and overall survival at 4-years were 77% and 67%, respectively. The Age-adjusted Charlson Comorbidity Index (aaCCI) correlated with failures (P = 0·007) with patients scoring ≤7 having a longer TTF (66% vs. 29%; P = 0·009). R-COMP-14 is feasible and ensures a substantial DFS to poor-risk DLBCL patients who would have been denied anthracycline-based treatment due to cardiac morbidity. The aaCCI predicted both treatment discontinuation rate and TTF.

Summary No robust biomarkers have been yet validated to identify the recurrence of disease in classical Hodgkin Lymphoma (cHL) patients upon induction treatment. The relevance of the inflammatory microenvironment in cHL prompted us to investigate the key immunomodulator myeloid dendritic cells type‐1 (mDC1), type‐2 (mDC2) and plasmacytoid dendritic cells (pDC). Blood DC levels were assessed in 52 newly diagnosed patients through multiparametric flow‐cytometry. All but two patients received ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine). The median counts of all DC subsets were lower in cHL patients than in healthy controls (P < 0·001). Median mDC counts were inferior for the advanced vs early stage patients for both mDC1s and mDC2s (P = 0·008; P = 0·0007 respectively). Also, median mDC2 counts were reduced in case of bulky (P = 0·0004) and extra‐nodal (P = 0·046) disease. Patients with B symptoms had lower levels for mDC1s (P = 0·046), mDC2s (P = 0·009) and pDCs (P = 0·040). All the DC subtypes increased at the end of treatment in 26 patients (P < 0·001): 4·6‐fold for mDC1, 2·4‐fold for mDC2, 4·5‐fold for pDC and aligned DCs subsets with the reference frequencies and the interquartile ranges of the controls. In conclusion, DCs may contribute to the disturbed immunological interplay typical of cHL, prompting a further evaluation of their value as a potential new biomarker.

No abstract

Sickle-cell disease is not a reportable condition, making it difficult to ascertain the number of affected individuals. We estimated the number of people with sickle-cell disease for the United States and each individual state, adjusting for increased mortality. US Census population data for each of the 50 states plus the District of Columbia were obtained. The published prevalence of sickle-cell disease for blacks and Hispanics of either Mexican or non-Mexican ancestry was applied. Analysis revealed 89,079 (95% confidence interval: 88,494-89,664) people with sickle-cell disease in the United States, 80,151 black and 8928 Hispanic. The state with the highest sickle-cell population was New York with 8308, followed by Florida with 7539, and Texas with 6765 people with sickle-cell disease. This study provides important information for researchers and policymakers attempting to better plan for the care of the sickle-cell population. Sickle-cell disease is the most common inherited blood disorder in the United States. It is responsible for approximately 113,000 hospitalizations and $488 million dollars in hospitalization costs annually in the United States [1]. Although sickle-cell disease is a genetic disease diagnosed in this era by newborn screening, it is not a reportable condition. Therefore, it is difficult to ascertain the number of affected individuals in the United States. Newborn screening is an effective tool for diagnosis, but its use was not widespread until the late 1980s and 1990s [2], and it does not account for immigration. Further complicating population estimates is the increased mortality associated with the disease, both compared to the mortality for the underlying racial/ethnic group and when comparing more severe forms of the disease (hemoglobin SS (HgbSS) and hemoglobin S beta thalessemia (HgbSB 0)) to less severe forms of the disease (hemoglobin SC (HgbSC) and HgbSB 1) [3-7]. Recent advances such as prophylactic penicillin and vaccines have reduced mortality, but only for those young enough to have received the treatments [8,9]. While no published studies have estimated the prevalence of sickle-cell disease in the United States, one NIH estimate puts the number ''between 50,000 and 75,000;'' another at 80,000, and the Sickle Cell Disease Association of America estimates the number to be ''over 70,000'' [10-12] Methods Census level-data and prevalence. Census data by age and race/ethnicity were obtained for each individual state and the District of Columbia and summed to equal the United States as a whole [13]. Year 2005 was used as the baseline. The applied prevalence rate of sickle-cell disease for blacks was 289 per 100,000 live births [14]. Prevalence rates for Hispanics were 89.8 Hispanic children of non-Mexican ancestry per 100,000 live births and 3.14 Hispanic children of Mexican ancestry per 100,000 live births [14]. These prevalence rates were applied to the Hispanic population numbers in each state based on the state's ratio of the number of Mexican births to non-Mexican births, assum...