Congenital Erythrocytosis (CE), also called congenital polycythemia, represents a rare and heterogeneous clinical entity. It is caused by deregulated red blood cell production where erythrocyte overproduction results in elevated hemoglobin and hematocrit levels. 3Primary congenital familial erythrocytosis is associated with low erythropoietin (Epo) levels and generally results from mutations in the erythropoietin-receptor gene (EPOR).Secondary congenital erythrocytosis arises from conditions which cause tissue hypoxia thus resulting in increased Epo production. These include hemoglobin variants with increased affinity for oxygen (genes HBB, HBA1 and HBA2), decreased production of 2,3-biphosphoglycerate due to mutations in the BPGM gene, or mutations in the genes involved in the hypoxia sensing pathway (VHL, EPAS1 and EGLN1). Depending on the affected gene CE can be inherited either in an autosomal dominant or recessive mode, with sporadic cases arising de novo.Despite recent important discoveries in the molecular pathogenesis of CE, the molecular causes remain to be identified in about 70% of the patients.With the objective of collecting all the published and unpublished cases of CE the COST action MPN&MPNr-Euronet developed a comprehensive internet-based database focusing on the registration of clinical history, hematological, biochemical and molecular data (http://www.erythrocytosis.org/). In addition, unreported mutations are also curated in the corresponding Leiden Open Variation Database (LOVD).

Combination chemotherapy may induce remission from acute myeloid leukemia (AML), but validated criteria for treatment of elderly are lacking. The remission intention (RI) rate for elderly patients, as reported to the Swedish Leukemia Registry, was known to be different when comparing the six health care regions, but the consequences of different management are unknown. The Leukemia Registry, containing 1672 AML patients diagnosed between 1997 and 2001, with 98% coverage and a median follow-up of 4 years, was completed with data from the compulsory cancer and population registries. Among 506 treated and untreated patients aged 70-79 years with AML (non-APL), there was a direct correlation between the RI rate in each health region (range 36-76%) and the two-year overall survival, with no censored observations (6-21%) (v 2 for trend ¼ 11.3, Po0.001; r 2 ¼ 0.86, Po0.02, nonparametric). A 1-month landmark analysis showed significantly better survival in regions with higher RI rates (P ¼ 0.003). Differences could not be explained by demographics, and was found in both de novo and secondary leukemias. The 5-year survival of the overall population aged 70-79 years was similar between the regions. Survival of 70-79-year-old AML patients is better in regions where more elderly patients are judged eligible for remission induction.

BackgroundA minority of patients with adult acute lymphoblastic leukemia who relapse are rescued. The aim of this population-based study was to assess the results of reinduction treatment and allogeneic stem cell transplantation in patients in second complete remission. Between 2003Between -2007 adults (<66 years) with relapsed acute lymphoblastic leukemia (Burkitt's leukemia excluded) were prospectively reported to The Swedish Adult Acute Leukemia Registry and later evaluated. Design and Methods ResultsReinduction with: (i) mitoxantrone, etoposide, and cytarabine (MEA); (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor (FLAG-Asp); and (iii) cytarabine, betamethasone, cyclophosphamide, daunorubicin, and vincristine (ABCDV) resulted in complete remission in 6/9 (67%), 10/16 (63%) and 9/21 (43%) of the patients, respectively. Allogeneic stem cell transplantation was performed during second complete remission in 29 patients. Multivariate analysis regarding overall survival after relapse revealed that age over 35 years at diagnosis and relapse within 18 months were negative prognostic factors. Overall survival rates at 3 and 5 years were 22% (95% CI: 13-32) and 15% (95% CI: 7-24). Of 19 patients less than 35 years at diagnosis who underwent allogeneic stem cell transplantation in second remission, ten (53%) are still alive at a median of 5.5 years (range, 4.2-8.3) after relapse, whereas all patients over 35 years old at diagnosis have died. ConclusionsAllogeneic stem cell transplantation remains the treatment of choice for young adults with relapsed acute lymphoblastic leukemia. Both (i) mitoxantrone, etoposide, and cytarabine and (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor seem effective as reinduction treatments and should be further evaluated. New salvage strategies are needed, especially for patients over 35 years old at diagnosis. Sweden 2003. Haematologica 201297(9):1414-1421. doi:10.3324/haematol.2011 This is an open-access paper. © F e r r a t a S t o r t i F o u n d a t i o n © F e r r a t a S t o r t i F o u n d a t i o n High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003-2007

/L and age ≥75 years were adverse prognostic factors for OS, Ph+ was not.Male sex was an adverse prognostic factor in the 55-64 year age-group. Conclusions:We report a high frequency of Ph+ in older/elderly patients, with no evidence of poorer outcome compared to Ph-negative disease. Overall prognosis for elderly patients with ALL remains dismal, despite the use of age-adapted treatment. K E Y W O R D Sacute lymphoblastic leukemia, chemotherapy, elderly, epidemiology

During recent years, the increasing knowledge of genetic and physiological changes in polycythemia vera (PV) and of different types of congenital erythrocytosis has led to fundamental changes in recommendations for the diagnostic approach to patients with erythrocytosis. Although widely accepted for adult patients this approach may not be appropriate with regard to children and adolescents affected by erythrocytosis. The "congenital erythrocytosis" working group established within the framework of the MPN&MPNr-EuroNet (COST action BM0902) addressed this question in a consensus finding process and developed a specific algorithm for the diagnosis of erythrocytosis in childhood and adolescence which is presented here.