Subsequent malignancies among long‐term survivors of Hodgkin lymphoma and non‐Hodgkin lymphoma: a pooled analysis of German cancer registry data (1990–2012)

The increased risk of subsequent primary malignancies (SPM) in survivors of adult‐onset Hodgkin lymphoma (HL) and non‐Hodgkin lymphoma (NHL) remains a challenging clinical problem worldwide. The German cancer registry database, pooled from 14 federal states, was used to calculate the standardized incidence ratio (SIR) and excess absolute risk (EAR) of SPM in 128 587 patients registered with first primary HL/NHL between 1990 and 2012. Conversely, SIRs were also calculated for a subsequent HL/NHL following other first cancers. The risk of developing SPM was significantly increased over twofold for HL survivors (SIR = 2·14, EAR = 51·87 cases/10 000 person‐years) and 1·5‐fold for NHL survivors (SIR = 1·48, EAR = 55·23) compared with the general German population. For solid cancers, SIRs were significantly elevated (1·6‐ and 1·4‐fold; respectively) and were highest (threefold) in patients below 30 years of age upon initial diagnosis. Overall, SIRs were consistently elevated for lip/oral cavity, colon/rectum, lung, skin melanoma, breast, kidney and thyroid. Significantly increased SIRs for oesophagus, stomach, liver, pancreas, testis, prostate, and brain/central nervous system were observed following NHL only. For certain SPM, SIRs remained significantly elevated more than 10 years following HL/NHL diagnosis. Positive reciprocal associations were demonstrated between HL/NHL and several solid cancers mentioned above; for some, common aetiological mechanisms seem plausible.     

Iatrogenic immunosuppression and risk of non‐Hodgkin lymphoma in solid organ transplantation: A population‐based cohort study in Australia

Iatrogenic immunosuppression is a strong risk factor for non‐Hodgkin lymphoma (NHL) but the dose‐related association between individual immunosuppressive agents and NHL risk is unknown. We conducted a population‐based cohort study of 4131 adult Australian liver, heart and lung transplant recipients (1984–2006). We ascertained NHL incidence by probabilistic record linkage between transplant registries and the Australian Cancer Database, and abstracted risk factor data at transplantation and at regular intervals thereafter from medical records. We estimated adjusted hazard ratios (HR) for early (<1 year after transplantation; n = 29) and late (≥1 year; n = 61) NHL using the Fine and Gray proportional subdistribution hazards model that accounted for death as a competing risk. After adjustment for immunosuppression, the risk of both early and late NHL did not significantly differ by organ type. In final models, higher mean daily doses of azathioprine were associated with increased risk of both early [HR 2·20, 95% confidence interval (CI): 1·21–4·01] and late NHL (HR 1·78, 95% CI: 1·12–2·84). There was no association between any other maintenance immunosuppressive agent and NHL risk. This study provides evidence that differences in immunosuppression may explain variation in NHL incidence by organ type, and high doses of azathioprine may independently predict NHL risk.     

Chronic medical conditions and late effects following non-Hodgkin lymphoma in HIV-uninfected and HIV-infected adolescents and young adults: a population-based study

Little is known about the incidence of late effects following non-Hodgkin lymphoma (NHL) among adolescent and young adult (AYA, 15–39 years) survivors. Using data from the California Cancer Registry linked to hospital discharge, we estimated the cumulative incidence of late effects at 10 years among AYAs diagnosed with NHL during 1996–2012, who survived ≥2 years. Cox proportional-hazards models were used to investigate the influence of sociodemographic and clinical factors on the occurrence of late effects. Of 4392 HIV-uninfected patients, the highest incident diseases were: endocrine (18·5%), cardiovascular (11·7%), and respiratory (5·0%), followed by secondary primary malignancy (SPM, 2·6%), renal and neurologic (2·2%), liver/pancreatic (2·0%), and avascular necrosis (1·2%). Among the 425 HIV-infected survivors, incidence was higher for all late effects, especially over threefold increased risk of SPM, compared to HIV-uninfected patients (8·1% vs. 2·6%). In multivariable models for HIV-uninfected patients, public or no health insurance (vs. private), residence in lower socioeconomic neighbourhoods (vs. higher), and receipt of a haematopoietic stem cell transplant were associated with a greater risk of most late effects. Our findings of substantial incidence of late effects among NHL AYA survivors emphasise the need for longterm follow-up and appropriate survivorship care to reduce morbidity and mortality in this vulnerable population.     

A national study on conditional survival,excess mortality and second cancer after high dose therapy with autologous stem cell transplantation for non‐Hodgkin lymphoma

This national population‐based study aimed to investigate conditional survival and standardized mortality ratios (SMR) after high‐dose therapy with autologous stem‐cell transplantation (HDT‐ASCT) for non‐Hodgkin lymphoma (NHL), and to analyse cause of death, relapses and second malignancies. All patients ≥18 years treated with HDT‐ASCT for NHL in Norway between 1987 and 2008 were included (n = 578). Information from the Cause of Death Registry and Cancer Registry of Norway were linked with clinical data. The 5‐, 10‐ and 20‐year overall survival was 61% (95% confidence interval [CI] 56–64%), 52% (95%CI 48–56%) and 45% (95%CI 40–50%), respectively. The 5‐year survival conditional on having survived 2, 5 and 10 years after HDT‐ASCT was 81%, 86% and 93%. SMRs were 12·3 (95%CI 11·0–13·9), 4·9 (95%CI 4·1–5·9), 2·4 (95%CI 1·8–3·2) and 1·0 (95%CI 0·6–1·8) for the entire cohort and for patients having survived 2, 5 and 10 years after HDT‐ASCT respectively. Of the 281 deaths observed, 77% were relapse‐related. Treatment‐related mortality was 3·6%. The 10‐year cumulative incidence of second malignancies was 7·9% and standardized incidence ratio was 2·0 (95%CI 1·5–2·6). NHL patients treated with HDT‐ASCT were at increased risk of second cancer and premature death. The mortality was still elevated at 5 years, but after 10 years mortality equalled that of the general population.     

Classification of non‐Hodgkin lymphoma in South‐eastern Europe: review of 632 cases from the international non‐Hodgkin lymphoma classification project

The distribution of non‐Hodgkin lymphoma (NHL) subtypes varies around the world, but a systematic study of South‐eastern Europe (SEEU) has never been done. Therefore, we evaluated the relative frequencies of NHL subtypes in three SEEU countries – Croatia, Romania and Macedonia. Five expert haematopathologists reviewed 632 consecutive cases of newly diagnosed NHL from the three SEEU countries using the World Health Organization classification. The results were compared to 399 cases from North America (NA) and 580 cases from Western Europe (WEU). The proportions of B‐ and T‐cell NHL and the sex distribution in SEEU were similar to WEU and NA. However, the median ages of patients with low‐ and high‐grade B‐NHL in SEEU (60 and 59 years, respectively) were significantly lower than in NA (64 and 68 years, respectively; P < 0·05). SEEU had a significantly lower proportion of low‐grade B‐NHL (46·6%) and higher proportion of high‐grade B‐NHL (44·5%) compared to both WEU (54·5% and 36·4%, respectively) and NA (56·1% and 34·3%, respectively). There were no significant differences in the relative frequencies of T‐NHL subtypes. This study provides new insights into differences in the relative frequencies of NHL subtypes in different geographic regions. Epidemiological studies are needed to better characterize and explain these differences.     

Overall survival of children and adolescents with mature B cell non‐Hodgkin lymphoma who had refractory or relapsed disease during or after treatment with FAB/LMB 96: A report from the FAB/LMB 96 study group

We determined the risk factors associated with poor survival in children and adolescents with de novo mature B cell non‐Hodgkin lymphoma (B‐NHL) who had refractory or relapsed disease during or after the French‐American‐British mature lymphoma B (FAB/LMB) 96 multi‐agent chemotherapy. Among the 1 111 registered on study, 104 patients (9·4%) had refractory disease or disease relapse after first complete remission. Among these 104 patients, 28 (27%) patients had refractory disease and 76 (73%) had relapsed disease. The estimated 1‐ and 2‐year overall survival (OS) (95% confidence interval) was 31·5% (23·3–41·0%) and 22·3% (15·3–31·4%), respectively. Prognostic analysis of OS using a Cox multivariate model showed that factors independently associated with OS included lactate dehydrogenase ≥2 upper normal limit [hazard ratio (HR) = 2·86 (1·57–5·2), P = 0·0006]; time to failure (>6 months) [HR = 0·59 (0·36–0·97), P = 0·038]; and failure in bone marrow [HR = 2·78 (1·65–4·68), P = 0·0001]. New therapeutic strategies are required to significantly reduce refractory disease and disease relapse in patients with newly diagnosed mature B‐NHL and, more importantly, there is a critical need to develop novel retrieval approaches in patients with chemotherapy‐resistant disease.     

Relative frequency of non‐Hodgkin lymphoma subtypes in selected centres in North Africa,the middle east and India: a review of 971 cases

Comparative data regarding the distribution of non‐Hodgkin lymphoma (NHL) subtypes in North Africa, the Middle East and India (NAF/ME/IN) is scarce in the literature. In this study, we evaluated the relative frequencies of NHL subtypes in this region. Five expert haematopathologists classified 971 consecutive cases of newly‐diagnosed NHL from five countries in NAF/ME/IN. After review, 890 cases (91·7%) were confirmed to be NHL and compared to 399 cases from North America (NA). The male‐to‐female ratio was significantly higher in NAF/ME/IN (1·8) compared to NA (1·1; P< 0·05). The median ages of patients with low‐grade (LG) and high‐grade (HG) B‐NHL in NAF/ME/IN (56 and 52 years, respectively) were significantly lower than in NA (64 and 68 years, respectively). In NAF/ME/IN, a significantly lower proportion of LG B‐NHL (28·4%) and a higher proportion of HG B‐NHL (58·4%) were found compared to NA (56·1% and 34·3%, respectively). Diffuse large B‐cell lymphoma was more common in NAF/ME/IN (49·4%) compared to NA (29·3%), whereas follicular lymphoma was less common in NAF/ME/IN (12·4%) than in NA (33·6%). In conclusion, we found significant differences in NHL subtypes and clinical features between NAF/ME/IN and NA. Epidemiological studies are needed to better understand the pathobiology of these differences.     

Physical activity,obesity and survival in diffuse large B‐cell and follicular lymphoma cases

There is limited information concerning the impact of physical activity and obesity on non‐Hodgkin lymphoma (NHL) prognosis. We examined the associations between pre‐diagnosis physical activity and body mass index (BMI) with survival in 238 diffuse large B‐cell (DLBCL) and 175 follicular lymphoma cases, with follow‐up from 2000 to 2015. The most physically active DLBCL cases had 41% lower risk of dying in the follow‐up period than the least active [Hazard ratio (HR) = 0·59, 95% confidence interval (CI) = 0·36–0·96], while obese follicular lymphoma cases had a 2·5‐fold risk of dying (HR = 2·52, 95% CI = 1·27–5·00) compared with cases with normal BMI. NHL‐specific survival results were similar.     

Late mortality,secondary malignancy and hospitalisation in teenage and young adult survivors of Hodgkin lymphoma: report of the Childhood/Adolescent/Young Adult Cancer Survivors Research Program and the BC Cancer Agency Centre for Lymphoid Cancer

Late complications affecting Hodgkin lymphoma (HL) survivors are well described in paediatric and adult‐based publications. This study determined the late morbidity and mortality risk for 442 teenage and young adult (TYAs) 5‐year HL survivors, diagnosed at 15–24 years of age between 1970 and 1999, identified from the British Columbia Cancer Registry. Treatment details were abstracted from charts. Survivors and a matched comparison cohort were linked to provincial administrative health datasets until December 2006 and regression analysis was performed, providing risk ratios regarding mortality, secondary malignancy and morbidity causing hospitalisation. Sixty (13·6%) survivors experienced late mortality with excess deaths from secondary cancer [standardised mortality ratio (SMR) 18·6; 95% confidence interval (CI) 11–29·4] and non‐malignant disease (SMR 3·6; 95% CI 2·2–5·5). Excess secondary cancers (standardised incidence ratio 7·8; 95% CI 5·6–10·5) were associated with radiotherapy [Hazard ratio (HR) 2·7; 95% CI 1–7·7] and female gender (HR 1·8; 95% CI 1–3·4). Of 281 survivors treated between 1981 and 1999, 143 (51%) had morbidity resulting in hospitalisation (relative risk 1·45; 95% CI 1·22–1·73). Hospitalisation significantly increased with combined modality therapy, chemotherapy alone and recent treatment era. TYA HL survivors have excess risk of mortality and secondary malignancy continuing 30 years from diagnosis. Radiotherapy is associated with secondary malignancy and current response‐adapted protocols attempt to minimise exposure, but late morbidity causing hospitalisation remains significant.     

Non‐Hodgkin lymphoma in Southern Africa: review of 487 cases from The International Non‐Hodgkin Lymphoma Classification Project

Comparative data on the distribution of non‐Hodgkin lymphoma (NHL) subtypes in Southern Africa (SAF) is scarce. In this study, five expert haematopathologists classified 487 consecutive cases of NHL from SAF using the World Health Organization classification, and compared the results to North America (NA) and Western Europe (WEU). Southern Africa had a significantly lower proportion of low‐grade (LG) B‐NHL (34·3%) and a higher proportion of high‐grade (HG) B‐NHL (51·5%) compared to WEU (54·5% and 36·4%) and NA (56·1% and 34·3%). High‐grade Burkitt‐like lymphoma was significantly more common in SAF (8·2%) than in WEU (2·4%) and NA (2·5%), most likely due to human immunodeficiency virus infection. When SAF patients were divided by race, whites had a significantly higher frequency of LG B‐NHL (60·4%) and a lower frequency of HG B‐NHL (32·7%) compared to blacks (22·5% and 62·6%), whereas the other races were intermediate. Whites and other races had a significantly higher frequency of follicular lymphoma and a lower frequency of Burkitt‐like lymphoma compared to blacks. The median ages of whites with LG B‐NHL, HG B‐NHL and T‐NHL (64, 56 and 67 years) were significantly higher than those of blacks (55, 41 and 34 years). Epidemiological studies are needed to better understand these differences.     

Chronic myeloproliferative neoplasms and risk of osteoporotic fractures; a nationwide population‐based cohort study

Patients with systemic mastocytosis have an increased risk of osteoporosis, however, the risk of osteoporotic fractures among the classic chronic myeloproliferative neoplasms (CMPN), including essential thrombocythaemia (ET), polycythaemia vera (PV) and chronic myeloid leukaemia (CML), is unknown. We conducted a population‐based cohort study to determine the risk of osteoporotic fractures among three cohorts of patients with newly diagnosed ET, PV, and CML. Patients were identified in medical registers including all Danish hospitals during 1980–2010 and were followed until first osteoporotic fracture. Fracture risk was compared to cohorts from the general population matched on age, sex and calendar year. We followed 7595 CMPN patients and 338 974 comparison cohort members. We found that the risk of femoral fracture after 5 years was consistently higher than the general population, being 3·01% (95% confidence interval (CI): 2·20–4·10), 4·74% (95%CI: 4·06–5·52) and 4·64% (95%CI: 3·29–6·53) among ET, PV, and CML patients respectively. Adjusted hazard ratio for femoral fracture was increased 1·19‐fold (95% CI: 0·94–1·51) for ET patients, 1·82‐fold (95% CI: 1·62–2·04) for PV patients, and 2·67‐fold (95% CI: 1·97–3·62) for CML patients. We conclude that CMPN patients are at higher risk of osteoporotic fractures than the general population.     

Peripheral T‐cell lymphoma in HIV‐infected patients: a study of 17 cases in the combination antiretroviral therapy era

Most cases of human immunodeficiency virus (HIV)‐associated non‐Hodgkin Lymphoma (NHL) are of B‐cell origin; T‐cell NHLs are rarely reported. Within a single centre prospective cohort of 370 HIV‐NHL, 17 (5%) were of T‐cell origin (82% male; median age, 39 years). Median CD4+ cell count was 0·194 × 10⁹/l and 41% had undetectable plasma HIV‐RNA at lymphoma diagnosis. All patients received combination antiretroviral therapy during chemotherapy. All histological samples were centrally reviewed. The distribution of the histological subtypes differed from the general population with absence of angioimmunoblastic subtype. Lymphoma was disseminated in 14 patients, and seven patients had performance status >2. All patients received full‐dose chemotherapy: eight standard and nine intensive regimens. Two patients who received intensive chemotherapy died during therapy. The complete remission rate was 53%; 62·5% with standard therapy and 44% with intensive therapy. After a median follow‐up of 7·2 years, the median overall survival was 9·4 months. Most deaths (85%) occurred within the first year following diagnosis, as a consequence of lymphoma progression in 10/13 cases. In this rare but severe complication of HIV infection the use of intensive chemotherapy does not appear to be beneficial for response, with increased toxicity.     

Second malignancies following treatment of chronic myeloid leukaemia in the tyrosine kinase inhibitor era

Given that tyrosine kinase inhibitors (TKIs) have dramatically improved the survival of patients with chronic myeloid leukaemia (CML), we were interested in examining the possible risk of long‐term adverse events, such as the emergence of other neoplasms. Therefore, we studied the development of second malignancies in 868 patients diagnosed with CML between 2002 and 2011 using the Swedish CML register, cross‐linked to the Swedish Cancer register. With a median follow‐up of 3·7 (range 0–9·9) years, 65 (7·5%) patients developed 75 second malignancies (non‐haematological), 52 of which were of the invasive type. Compared to expected rates in the background population, the risk of second malignancies was higher in the CML cohort, with a standardized incidence ratio (SIR) of 1·52 (95% CI 1·13–1·99). The SIR before and after the second year following diagnosis of CML was 1·58 and 1·47, respectively. Among specific cancer types, gastrointestinal and nose and throat cancer were significantly increased. Founded on a population‐based material, our results indicate that CML patients treated in the TKI era are at an increased risk of developing a second malignancy, with indications that this risk may more likely be linked to CML itself rather than to the TKI treatment.     

Second primary malignancy after multiple myeloma‐population trends and cause‐specific mortality

The management of multiple myeloma (MM) has evolved with the increased use of autologous haematopoietic cell transplantation (AHCT) and the introduction of new agents. AHCT and lenalidomide maintenance have been associated with increased risk of second primary malignancy (SPM). We iseutilised the Surveillance, Epidemiology and End Results 13 registries to analyse 9 833 patients diagnosed at age <65 years for three eras: 1995–99 (pre‐thalidomide, limited use of AHCT), 2000–04 (post‐thalidomide, pre‐lenalidomide and bortezomib, increased isautilisation of AHCT) and 2005–09 (post‐lenalidomide and bortezomib, higher isautilisation of AHCT). Changes in risk of SPM were assessed by utilising standardised incidence ratio (SIR) and cause‐specific risk of death. Cumulative incidence of SPM at 90 months was 4·7%, 6·0% and 6·3% respectively, P = 0·0008. SIR for haematological malignancies in years 1–5 increased, from 1·28 (95% confidence interval [CI] 0·47–2·78) in 1995–99 to 2·17 (95% CI: 1·27–3·48) in 2005–09, due to increased risk of acute leukaemias and lymphomas. A similar trend was observed in years 6–10. Overall mortality in patients with MM declined sharply over time due to declines in MM‐associated and cardiovascular mortality with no increase in risk of death from SPM. The evolution of MM therapy is linked to population‐level increase in risk with no discernible effect in death from SPM.     

Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B‐cell non‐Hodgkin lymphoma: post‐hoc analyses from a phase III trial

This post hoc analysis of a phase 3 trial explored the effect of pixantrone in patients (50 pixantrone, 47 comparator) with relapsed or refractory aggressive B‐cell non‐Hodgkin lymphoma (NHL) confirmed by centralized histological review. Patients received 28‐d cycles of 85 mg/m² pixantrone dimaleate (equivalent to 50 mg/m² in the approved formulation) on days 1, 8 and 15, or comparator. The population was subdivided according to previous rituximab use and whether they received the study treatment as 3rd or 4th line. Median number of cycles was 4 (range, 2–6) with pixantrone and 3 (2–6) with comparator. In 3rd or 4th line, pixantrone was associated with higher complete response (CR) (23·1% vs. 5·1% comparator, P = 0·047) and overall response rate (ORR, 43·6% vs. 12·8%, P = 0·005). In 3rd or 4th line with previous rituximab (20 pixantrone, 18 comparator), pixantrone produced better ORR (45·0% vs. 11·1%, P = 0·033), CR (30·0% vs. 5·6%, P = 0·093) and progression‐free survival (median 5·4 vs. 2·8 months, hazard ratio 0·52, 95% confidence interval 0·26–1·04) than the comparator. Similar results were found in patients without previous rituximab. There were no unexpected safety issues. Pixantrone monotherapy is more effective than comparator in relapsed or refractory aggressive B‐cell NHL in the 3rd or 4th line setting, independently of previous rituximab.     

Metabolic syndrome and cardiovascular risk among long‐term survivors of acute lymphoblastic leukaemia ‐ From the St. Jude Lifetime Cohort

Adult survivors of childhood acute lymphoblastic leukaemia (ALL) have a four‐fold excess risk of mortality from cardiovascular disease. This cardiovascular risk has not been fully characterized. ALL survivors [n = 784, median age 31·7 years (18·9–59·1)] in the St. Jude Lifetime Cohort Study underwent evaluation for cardiovascular risk and metabolic syndrome (MetS) according to National Cholesterol Education Program – Adult Treatment Panel III criteria. Comparisons were made to 777 age‐, sex‐, and race‐matched controls from the National Health and Nutrition Examination Survey (NHANES). MetS was identified in 259 survivors (33·6%) and associated with older age in 5‐year increments (relative risk [RR] 1·13, 95% confidence interval [CI] 1·06–1·19) and prior cranial radiotherapy (CRT) (with craniospinal radiation: RR 1·88, 95%CI 1·32–2·67; without: RR 1·67, 95%CI 1·26–2·23). Measures of obesity were highly prevalent among female survivors and CRT recipients. Compared to NHANES controls, ALL survivors had a higher risk of MetS (RR 1·43, 95%CI 1·22–1·69), hypertension (RR 2·43, 95%CI 2·06–2·86), low high‐density lipoprotein (RR 1·40, 95%CI 1·23–1·59), obesity (RR 1·47, 95%CI 1·29–1·68) and insulin resistance (1·64, 95%CI 1·44–1·86). This large study of clinically evaluated ALL survivors identified a high prevalence of MetS, obesity and cardiovascular risk, particularly in CRT recipients, underscoring the need for screening and aggressive reduction of modifiable risks.     

Pre‐transplant comorbidity burden and post‐transplant chronic graft‐versus‐host disease

The Haematopoietic Cell Transplantation‐Comorbidity Index (HCT‐CI) was designed as a predictor of non‐relapse mortality after HCT. Chronic graft‐versus‐host disease (GVHD) contributes to mortality after HCT. Here, we investigated whether the HCT‐CI could predict development of chronic GVHD or post‐chronic GVHD mortality. We retrospectively analysed data from 2909 patients treated with allogeneic HCT for malignant and non‐malignant haematological conditions at four institutions. In Cox regression models adjusted for potential confounders, increasing HCT‐CI was not statistically significantly associated with the development of chronic GVHD [hazard ratio (HR) = 1·02, P = 0·34]. Yet, the index was associated with an increased risk of non‐relapse mortality (HR = 1·29, P < 0·0001) as well as overall mortality (HR = 1·25, P < 0·001) following the development of chronic GVHD. The association between HCT‐CI and post‐chronic GVHD mortality was similar regardless of donor type or stem cell source. HCT‐CI scores could be incorporated in the design of clinical trials for treatment of chronic GVHD.     

Prognostic significance of flow‐cytometry evaluation of minimal residual disease in children with acute myeloid leukaemia treated according to the AIEOP‐AML 2002/01 study protocol

In children with acute myeloid leukaemia (AML ), assessment of initial treatment response is an essential prognostic factor; methods more sensitive than morphology are still under evaluation. We report on the measurement of minimal residual disease (MRD ), by multicolour flow‐cytometry in one centralized laboratory, in 142 children with newly diagnosed AML enrolled in the Associazione Italiana di EmatoOncologia Pediatrica‐AML 2002/01 trial. At the end of the first induction course, MRD was <0·1% in 69, 0·1–1% in 16 and >1% in 51 patients. The 8‐year disease‐free survival (DFS ) of 125 children in morphological complete remission and with MRD <0·1%, 0·1–1% and ≥1% was 73·1 ± 5·6%, 37·8 ± 12·1% and 34·1 ± 8·8%, respectively (P  < 0·01). MRD was also available after the second induction course in 92/142 patients. MRD was ≥0·1% at the end of the first induction course in 36 patients; 13 reached an MRD <0·1% after the second one and their DFS was 45·4 ± 16·7% vs. 22·8 ± 8·9% in patients with persisting MRD ≥0·1% (P  = 0·037). Multivariate analysis demonstrated that MRD ≥0·1% after first induction course was, together with a monosomal karyotype, an independent adverse prognostic factor for DFS . Our results show that MRD detected by flow‐cytometry after induction therapy predicts outcome in patients with childhood AML and can help stratifying post‐remission treatment.     

Risks,severity and timing of infections in patients with multiple myeloma: a longitudinal cohort study in the era of immunomodulatory drug therapy

We defined the epidemiology and clinical predictors of infection in patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs), proteasome inhibitors (PI) and autologous haematopoietic stem cell transplant (ASCT) in a large longitudinal cohort study. Clinical and microbiology records of patients with MM diagnosed between January 2008 and December 2012 were reviewed to capture patient demographics, characteristics of myeloma and infections (type, severity, outcomes). Conditional risk set modelling was used to determine clinical predictors of infection. One hundred and ninety‐nine patients with MM with 771 episodes of infection were identified. 44·6% of infections were clinically defined, 35·5% were microbiologically defined and 19·9% were fever of unknown focus. There was a bimodal peak in incidence of bacterial (4–6 and 70–72 months) and viral infections (7–9 and 52–54 months) following disease diagnosis. Chemotherapy regimens high‐dose melphalan [hazard ratio (HR) = 2·07], intravenous cyclophosphamide (HR = 1·96) and intensive combination systemic chemotherapy (HR = 1·86) and cumulative doses of corticosteroid (HR = 3·06 at highest dose) were independently associated with increased risk of infection overall (P < 0·05). IMiDs and PI and other clinical factors were not independently associated with increased risk of infection. New approaches to prevention and treatment of infection should focus upon identified periods of risk and treatment‐related risk factors.     

Age disparities in survival from lymphoma and myeloma: a comparison between US and England

Population‐level survival in older patients with lymphoma is significantly lower than in younger patients. In this study, data were obtained from cancer registries in England and the United States (US) for patients diagnosed with Hodgkin lymphoma (HL), non‐Hodgkin lymphoma (NHL) and myeloma. Five‐year relative survival was calculated using period analysis. Generalised linear models were used to determine excess hazard ratios (EHR) for older compared to younger patients. Five‐year relative survival was lower for older patients diagnosed with HL, NHL and myeloma in both countries. The greatest age‐related survival inequality was observed for patients with HL: in 2006–10 the EHR comparing patients aged 75 + years with those aged 15–24 years was 14·02 in the US and 15·69 in England. For NHL, the EHR was 1·91 in the US and 3·81 in England. For myeloma, comparing patients aged 75 + years with those aged 25–44 years, the EHR was 2·79 in the US and 3·60 in England. Survival of patients with lymphoma is lower for older patients in both the US and England but the discrepancy is less in the US. Physicians should be encouraged to evaluate patients' frailty and co‐morbidities as well as their age when considering treatment options for patients with lymphoma and myeloma.