Publications by authors named "Lucio Luzzatto"

107 Publications

Paroxysmal nocturnal haemoglobinuria (PNH): novel therapies for an ancient disease.

Br J Haematol 2020 Nov;191(4):579-586

Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK.

In the UK, early work on paroxysmal nocturnal haemoglobinuria (PNH) was conducted by John Dacie who, at the Hammersmith Hospital, first hypothesised that the PNH abnormality might arise through a somatic mutation; and who outlined with S.M. Lewis the relationship between PNH and aplastic anaemia. When the phosphatidylinositol glycan anchor biosynthesis Class A (PIGA) gene was identified by Taroh Kinoshita's group, jointly with him the Hammersmith group proved that PNH is caused in most patients by a single somatic mutation in the PIGA gene. At the same time, after Bruno Rotoli had spent a sabbatical at the Hammersmith, the 'immune escape model' for the pathogenesis of PNH was developed. Early this century, Peter Hillmen, formerly at the Hammersmith and now in Leeds, spearheaded the use of the complement-blocking (anti-C5) antibody eculizumab. This new medicine radically changed the management and the clinical course of patients with PNH. Recently a derivative of eculizumab with more favourable pharmacokinetics has been introduced. In view of the fact that these agents are associated with C3-dependent extravascular haemolysis, it is important that a number of inhibitors of the proximal complement pathway are now in the offing and may further improve the life of patients with PNH.
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http://dx.doi.org/10.1111/bjh.17147DOI Listing
November 2020

F cell numbers are associated with an X-linked genetic polymorphism and correlate with haematological parameters in patients with sickle cell disease.

Br J Haematol 2020 Dec 19;191(5):888-896. Epub 2020 Oct 19.

Muhimbili Sickle Cell Programme, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.

Patients with sickle cell disease (SCD) with high fetal haemoglobin (HbF) tend to have a lower incidence of complications and longer survival due to inhibition of deoxyhaemoglobin S (HbS) polymerisation by HbF. HbF-containing cells, namely F cells, are strongly influenced by genetic factors. We measured the percentage of F cells (Fcells%) in 222 patients with SCD to evaluate the association of (i) Fcells% with genetic HbF-modifier variants and (ii) Fcells% with haematological parameters. There was a different distribution of Fcells% in females compared to males. The association of the B-cell lymphoma/leukaemia 11A (BCL11A) locus with Fcells% (β = 8·238; P < 0·001) and with HbF% (β = 2·490; P < 0·001) was significant. All red cell parameters except for Hb and mean corpuscular Hb concentration levels in males and females were significantly different. The Fcells% was positively associated with mean cell Hb, mean cell volume and reticulocytes. To explain the significant gender difference in Fcells%, we tested for associations with single nucleotide polymorphisms on the X chromosomal region Xp22.2, where a genetic determinant of HbF had been previously hypothesised. We found in males a significant association with a SNP in FERM and PDZ domain-containing protein 4 (FRMPD4) and adjacent to male-specific lethal complex subunit 3 (MSL3). Thus, we have identified an X-linked locus that could account for a significant fraction of the Fcells% variation in patients with SCD.
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http://dx.doi.org/10.1111/bjh.17102DOI Listing
December 2020

Making hydroxyurea affordable for sickle cell disease in Tanzania is essential (HASTE): How to meet major health needs at a reasonable cost.

Am J Hematol 2021 01 6;96(1):E2-E5. Epub 2020 Oct 6.

Department of Haematology, Muhimbili University of Health and Allied Sciences, Dar-es-Salaam, Tanzania.

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http://dx.doi.org/10.1002/ajh.26007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756644PMC
January 2021

Complement-mediated oxidative damage of red cells impairs response to eculizumab in a G6PD-deficient patient with PNH.

Blood 2020 Dec;136(26):3082-3085

Laboratory of Cancer Genetics and Gene Transfer, Core Research Laboratory-Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.

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http://dx.doi.org/10.1182/blood.2020007780DOI Listing
December 2020

Glucose-6-phosphate dehydrogenase deficiency.

Blood 2020 Sep;136(11):1225-1240

Laboratory of Cancer Genetics and Gene Transfer, Core Research Laboratory, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.

Glucose 6-phosphate dehydrogenase (G6PD) deficiency is 1 of the commonest human enzymopathies, caused by inherited mutations of the X-linked gene G6PD. G6PD deficiency makes red cells highly vulnerable to oxidative damage, and therefore susceptible to hemolysis. Over 200 G6PD mutations are known: approximately one-half are polymorphic and therefore common in various populations. Some 500 million persons with any of these mutations are mostly asymptomatic throughout their lifetime; however, any of them may develop acute and sometimes very severe hemolytic anemia when triggered by ingestion of fava beans, by any of a number of drugs (for example, primaquine, rasburicase), or, more rarely, by infection. Approximately one-half of the G6PD mutations are instead sporadic: rare patients with these mutations present with chronic nonspherocytic hemolytic anemia. Almost all G6PD mutations are missense mutations, causing amino acid replacements that entail deficiency of G6PD enzyme activity: they compromise the stability of the protein, the catalytic activity is decreased, or a combination of both mechanisms occurs. Thus, genotype-phenotype correlations have been reasonably well clarified in many cases. G6PD deficiency correlates remarkably, in its geographic distribution, with past/present malaria endemicity: indeed, it is a unique example of an X-linked human polymorphism balanced through protection of heterozygotes from malaria mortality. Acute hemolytic anemia can be managed effectively provided it is promptly diagnosed. Reliable diagnostic procedures are available, with point-of-care tests becoming increasingly important where primaquine and its recently introduced analog tafenoquine are required for the elimination of malaria.
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http://dx.doi.org/10.1182/blood.2019000944DOI Listing
September 2020

Sickle cell disease and malaria: decreased exposure and asplenia can modulate the risk from Plasmodium falciparum.

Malar J 2020 Apr 25;19(1):165. Epub 2020 Apr 25.

Department of Hematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.

Background: Patients with sickle cell disease (SCD), an inherited haemoglobinopathy, have increased risk of malaria, at least in part due to impaired splenic function. Infection with Plasmodium falciparum in SCD patients can trigger painful vaso-occlusive crisis, increase the severity of anaemia, and contribute to early childhood mortality.

Case Presentation: A 17 year-old Tanzanian male with known SCD was admitted to Muhimbili National Hospital, a tertiary referral centre in Dar-es-Salaam, following an attack of malaria. From 2004 to 2007 the patient had lived in USA, and from 2010 to 2016 in France where, on account of hypersplenism and episodes of splenic sequestrations, in 2014 the spleen was removed. After appropriate clinical and laboratory assessment the patient was re-started on hydroxyurea; and anti-malarial-prophylaxis with proguanil was instituted. The patient has remained well and malaria-free for the following 15 months.

Conclusion: SCD patients are highly vulnerable to malaria infection, and impaired splenic function is a feature of SCD patients, even in those who still anatomically have a spleen. This patient had a surgical splenectomy and, in addition, had probably lost some of the acquired malaria-immunity by having lived for several years in malaria-free areas. This patient is a compelling reminder that long-term anti-malarial prophylaxis should be offered to all patients with SCD who live in malaria-endemic areas.
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http://dx.doi.org/10.1186/s12936-020-03212-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183641PMC
April 2020

PNH phenotypes and their genesis.

Authors:
Lucio Luzzatto

Br J Haematol 2020 06 12;189(5):802-805. Epub 2020 Mar 12.

Department of Haematology and Blood Tranfusion, Muhimbili University of Health and Allied Sciences, Dar-es-Salaam, Tanzania.

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http://dx.doi.org/10.1111/bjh.16473DOI Listing
June 2020

Tafenoquine for the prophylaxis, treatment and elimination of malaria: eagerness must meet prudence.

Future Microbiol 2019 10 9;14:1261-1279. Epub 2019 Oct 9.

Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Amazonas, 69040-000, Brazil.

Malaria puts more than 3 billion people at risk of infection and causes high morbidity and mortality. forms hypnozoites, which may initiate recurrences, even in the absence of reinfection or superinfection. Until recently, the only drug available for eliminating hypnozoites was primaquine (PQ), which, given its short half-life, requires a relatively long course of treatment. Tafenoquine (TQ) is a PQ analog with a longer half-life. This enables radical cure of malaria with a single dose and overcomes adherence issues associated with PQ, thereby increasing effectiveness in real-life settings. Clinical studies have provided sound evidence for TQ's safety and efficacy against malaria, which recently led to its approval by the US FDA. Here, we review aspects of TQ, including how to avoid hemolytic anemia in G6PD deficient patients. We believe that TQ promises to be a major advance toward malaria elimination.
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http://dx.doi.org/10.2217/fmb-2019-0202DOI Listing
October 2019

Diagnostic and therapeutic implements based on advanced Biotechnology should be available in low-income countries.

Acta Biomed 2019 09 30;90(10-S):5-6. Epub 2019 Sep 30.

EBTNA-LAB, Rovereto (TN), Italy; MAGI EUREGIO, Bolzano, Italy; Alliance for Health Promotion - in Official Relations with the World Health Organization (WHO), Geneva, Switzerland.

N.A.
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http://dx.doi.org/10.23750/abm.v90i10-S.8771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233641PMC
September 2019

Germline NPM1 mutations lead to altered rRNA 2'-O-methylation and cause dyskeratosis congenita.

Nat Genet 2019 10 30;51(10):1518-1529. Epub 2019 Sep 30.

Cancer Research Institute, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

RNA modifications are emerging as key determinants of gene expression. However, compelling genetic demonstrations of their relevance to human disease are lacking. Here, we link ribosomal RNA 2'-O-methylation (2'-O-Me) to the etiology of dyskeratosis congenita. We identify nucleophosmin (NPM1) as an essential regulator of 2'-O-Me on rRNA by directly binding C/D box small nucleolar RNAs, thereby modulating translation. We demonstrate the importance of 2'-O-Me-regulated translation for cellular growth, differentiation and hematopoietic stem cell maintenance, and show that Npm1 inactivation in adult hematopoietic stem cells results in bone marrow failure. We identify NPM1 germline mutations in patients with dyskeratosis congenita presenting with bone marrow failure and demonstrate that they are deficient in small nucleolar RNA binding. Mice harboring a dyskeratosis congenita germline Npm1 mutation recapitulate both hematological and nonhematological features of dyskeratosis congenita. Thus, our findings indicate that impaired 2'-O-Me can be etiological to human disease.
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http://dx.doi.org/10.1038/s41588-019-0502-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858547PMC
October 2019

Sickle cell disease, malaria and dengue fever: a case of triple jeopardy.

J Travel Med 2019 Oct;26(7)

Department of Haematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.

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http://dx.doi.org/10.1093/jtm/taz070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796044PMC
October 2019

Hypertensive disorders of pregnancy are associated with an inflammatory state: evidence from hematological findings and cytokine levels.

BMC Pregnancy Childbirth 2019 Jul 9;19(1):237. Epub 2019 Jul 9.

Department of Obstetrics and Gynaecology, Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania.

Background: Abnormalities of blood cell counts and of cytokine profiles in women with hypertensive disorders of pregnancy (HDP) have been reported in several studies. Although their cause-effect relationships to HDP are not yet clear, detecting and monitoring these alterations can be of use for prognosis and management of HDP. This study aimed to determine hematological, coagulation and cytokine profiles in hypertensive as compared to normotensive pregnancy and to identify correlations between these profiles.

Methods: This was a hospital-based comparative cross-sectional study conducted from September 2017 to February 2018. There were two groups: the comparison group consisted of 77 normotensive pregnant women attending the antenatal clinic of Muhimbili National Hospital (MNH); the index group consisted of 76 hypertensive pregnant women admitted to the maternity block of the same hospital. Hematological and cytokine parameters were compared between the hypertensive and the normotensive group. We analyzed the data using Student's independent t-test when the data were normally distributed; and the Mann-Whitney U-test when the data were not normally distributed. Kruskal Wallis with Dunn's multiple comparison tests was run for subgroup analysis and correlation studies were done using Spearman ranking.

Results: Hemoglobin levels were slightly but significantly lower, (P < 0.01) in women with HDP compared to normotensive (N) women; the same was true for platelet counts (P < 0.001). The red cell distribution width (RDW) was slightly but significantly higher in HDP than in N. Neutrophil counts and Interleukin 6 (IL-6) levels were significantly (P < 0.001) higher in HDP than in N; and within HDP IL-6 levels increased with increasing severity of HDP. A novel remarkable finding was that eosinophil counts, normal in N, were lower and lower with increasing severity of HDP, to the point that they were nearly absent in women with eclampsia.

Conclusion: There are significant changes in hematological, cytokine and coagulation parameters in pregnant women with hypertensive disorders compared to normotensive pregnant women. The picture that emerges is that of an inflammatory state associated with hypertensive disorders of pregnancy.
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http://dx.doi.org/10.1186/s12884-019-2383-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617701PMC
July 2019

[Drugs for rare diseases: the blessing of being orphans.]

Recenti Prog Med 2019 05;110(5):221-229

IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milano.

The incentives provided by Orphan Drugs Regulations have promoted the development of drugs that effectively ameliorate the course of serious conditions that had previously been neglected. However, the treatment of each individual patient with any of these drugs - the so-called 'orphan drugs' - is so expensive, that the total burden for publicly funded Health care Service is enormous and may become unsustainable. Italy is no exception, if it is to abide by its basic tenet of providing access to essential medicines - free of charge - to the entire population. We do not see any glimpses of improvement on the horizon: therefore we suggest that radical change must be introduced. First, price negotiation ought to take place at the European level, not at the member state level. Second, pricing should take into account not only value for patients, but also costs of research and development (R&D) plus production. Italian Medicines Agency (AIFA) should also support research focused on optimizing the effective use of orphan drugs in clinical practice. The challenges are complex: but AIFA is recognized as an authoritative body, and may be able to coagulate the agreement of other regulatory agencies for the ultimate purpose of achieving, for each of the orphan drugs a more reasonable 'European price'.
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http://dx.doi.org/10.1701/3163.31444DOI Listing
May 2019

Orphan drugs - Authors' reply.

Lancet 2019 04;393(10181):1595-1596

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy; Department of Clinical and Biomedical Sciences, University of Milan, Italy. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(19)30014-5DOI Listing
April 2019

Hydroxyurea - An Essential Medicine for Sickle Cell Disease in Africa.

N Engl J Med 2019 01;380(2):187-189

From the Department of Hematology and Sickle Cell Program, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.

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http://dx.doi.org/10.1056/NEJMe1814706DOI Listing
January 2019

High frequency of acquired aplastic anemia in Tanzania.

Am J Hematol 2019 04 6;94(4):E86-E88. Epub 2019 Feb 6.

Department of Haematology and Blood Transfusion, Muhimbili National Hospital and Muhimbili University of Health and Allied Sciences (MUHAS), Dar-es-Salaam, Tanzania.

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http://dx.doi.org/10.1002/ajh.25388DOI Listing
April 2019

A ten year review of the sickle cell program in Muhimbili National Hospital, Tanzania.

BMC Hematol 2018 14;18:33. Epub 2018 Nov 14.

1Muhimbili University of Health and Allied Sciences, Dar-es-Salaam, Tanzania.

Background: Africa has the highest burden of Sickle cell disease (SCD) but there are few large, systematic studies providing reliable descriptions of the disease spectrum. Tanzania, with 11,000 SCD births annually, established the Muhimbili Sickle Cell program aiming to improve understanding of SCD in Africa. We report the profile of SCD seen in the first 10 years at Muhimbili National Hospital (MNH).

Methods: Individuals seen at MNH known or suspected to have SCD were enrolled at clinic and laboratory testing for SCD, haematological and biochemical analyses done. Ethnicity was self-reported. Clinical and laboratory features of SCD were documented. Comparison was made with non-SCD population as well as within 3 different age groups (< 5, 5-17 and ≥ 18 years) within the SCD population.

Results: From 2004 to 2013, 6397 individuals, 3751 (58.6%) SCD patients, were enrolled, the majority (47.4%) in age group 5-17 years. There was variation in the geographical distribution of SCD. Individuals with SCD compared to non-SCD, had significantly lower blood pressure and peripheral oxygen saturation (SpO). SCD patients had higher prevalence of severe anemia, jaundice and desaturation (SpO < 95%) as well as higher levels of reticulocytes, white blood cells, platelets and fetal hemoglobin. The main causes of hospitalization for SCD within a 12-month period preceding enrolment were pain (adults), and fever and severe anemia (children). When clinical and laboratory features were compared in SCD within 3 age groups, there was a progressive decrease in the prevalence of splenic enlargement and an increase in prevalence of jaundice. Furthermore, there were significant differences with monotonic trends across age groups in SpO2, hematological and biochemical parameters.

Conclusion: This report confirms that the wide spectrum of clinical expression of SCD observed elsewhere is also present in Tanzania, with non-uniform geographical distribution across the country. Age-specific analysis is consistent with different disease-patterns across the lifespan.
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http://dx.doi.org/10.1186/s12878-018-0125-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236876PMC
November 2018

Outrageous prices of orphan drugs: a call for collaboration.

Lancet 2018 09 20;392(10149):791-794. Epub 2018 Jul 20.

IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy; Unit of Nephrology and Dialysis, Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy; Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(18)31069-9DOI Listing
September 2018

Limited Exchange Transfusion Can Be Very Beneficial in Sickle Cell Anemia with Acute Chest Syndrome: A Case Report from Tanzania.

Case Rep Hematol 2018 21;2018:5253625. Epub 2018 Jun 21.

Sickle Cell Programme, Department of Hematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.

Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD) with blood transfusion an integral part in its management. Red cell exchange (RCE) transfusion is usually regarded as preferable to top-up transfusion, because it reduces the proportion of Hemoglobin (Hb) S while at the same time avoiding circulatory overload. Despite its obvious benefits, RCE is underutilized, particularly in low-resource settings which may be due to scarcity of blood products and of expertise in carrying out exchange transfusion. We report on a young woman with SCD with severe ACS who responded promptly and dramatically to a RCE of only 0.95 L (instead of the recommended 1.4 L) and had in the end an HbS level of 48% (instead of the recommended level below 30%). Limited RCE resulted in significant clinical improvement. We suggest that limited RCE may be of benefit than no RCE in SCD patients with ACS, particularly in settings where RCE is not available.
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http://dx.doi.org/10.1155/2018/5253625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032970PMC
June 2018

Genes expressed in red cells could shape a malaria attack.

Authors:
Lucio Luzzatto

Lancet Haematol 2018 08 20;5(8):e322-e323. Epub 2018 Jul 20.

Department of Haematology, Muhimbili University of Health and Allied Sciences, Dar-es-Salaam, Tanzania. Electronic address:

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http://dx.doi.org/10.1016/S2352-3026(18)30110-8DOI Listing
August 2018

Advances in understanding the pathogenesis of acquired aplastic anaemia.

Br J Haematol 2018 09 5;182(6):758-776. Epub 2018 Jul 5.

Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.

This review examines the evidence that bone marrow failure (BMF) in aplastic anaemia (AA) is due to loss of haematopoietic stem cells (HSCs), which, in turn, is caused by deranged immunity and inflammation. We also consider how the course of the disease and the response to immuno-suppressive therapy are influenced by the nature and specificity of the pathogenic process. A somatic mutation of the PIGA gene underlies the clonal disease paroxysmal nocturnal haemoglobinuria (PNH): there is direct evidence that the expansion of the PIGA mutant clone results from Darwinian selection exerted by a glycosyl-phosphatidyl-inositol -specific auto-immune attack. Thus, PNH patients are a unique subset of patients with AA, in whom haematopoiesis recovers through this escape mechanism. A similar process, although less effective, may operate when the auto-immune attack is against a human leucocyte antigen (HLA) molecule and an HLA mutation has produced a clone missing that molecule. We then discuss the significance of other mutant clones that are frequently found in AA, presumably due to a combination of genetic drift and selection. These clones are not causative of AA, but they emerge in AA and they may be pre-leukaemic: unlike a PIGA mutant clone, in general they are unable to effectively reconstitute haematopoiesis.
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http://dx.doi.org/10.1111/bjh.15443DOI Listing
September 2018

Favism and Glucose-6-Phosphate Dehydrogenase Deficiency.

N Engl J Med 2018 03;378(11):1068-1069

University of Turin, Turin, Italy

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http://dx.doi.org/10.1056/NEJMc1801271DOI Listing
March 2018

Primaquine-induced haemolysis in females heterozygous for G6PD deficiency.

Malar J 2018 Mar 2;17(1):101. Epub 2018 Mar 2.

Department of Haematology, Muhimbili University of Health and Allied Sciences, Dar-es-Salaam, Tanzania.

Oxidative agents can cause acute haemolytic anaemia in persons with G6PD deficiency. Understanding the relationship between G6PD genotype and the phenotypic expression of the enzyme deficiency is necessary so that severe haemolysis can be avoided. The patterns of oxidative haemolysis have been well described in G6PD deficient hemizygous males and homozygous females; and haemolysis in the proportionally more numerous heterozygous females has been documented mainly following consumption of fava beans and more recently dapsone. It has long been known that 8-aminoquinolines, notably primaquine and tafenoquine, cause acute haemolysis in G6PD deficiency. To support wider use of primaquine in Plasmodium vivax elimination, more data are needed on the haemolytic consequences of 8-aminoquinolines in G6PD heterozygous females. Two recent studies (in 2017) have provided precisely such data; and the need has emerged for the development of point of care quantitative testing of G6PD activity. Another priority is exploring alternative 8-aminoquinoline dosing regimens that are practical and improve safety in G6PD deficient individuals.
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http://dx.doi.org/10.1186/s12936-018-2248-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833093PMC
March 2018

The "escape" model: a versatile mechanism for clonal expansion.

Br J Haematol 2019 02 24;184(3):465-466. Epub 2018 Jan 24.

Core Research Laboratory - ITT, AOU Careggi, Firenze, Italy.

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http://dx.doi.org/10.1111/bjh.15111DOI Listing
February 2019

Sterile 'Abscess' of the Spleen and the Sickle Cell Trait.

Authors:
Lucio Luzzatto

Mediterr J Hematol Infect Dis 2018 1;10(1):e2018003. Epub 2018 Jan 1.

Dept of Haematology and Blood Transfusion, Muhimbili University, Muhimbili National Hospital, Dar-es-Salaam, Tanzania.

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http://dx.doi.org/10.4084/MJHID.2018.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760069PMC
January 2018

Favism and Glucose-6-Phosphate Dehydrogenase Deficiency.

N Engl J Med 2018 01;378(1):60-71

From the Department of Hematology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania (L.L.); and the Department of Oncology, Biochemistry Unit, University of Turin, Turin, Italy (P.A.).

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http://dx.doi.org/10.1056/nejmra1708111DOI Listing
January 2018

The European Cancer Patient's Bill of Rights, update and implementation 2016.

ESMO Open 2016 6;1(6):e000127. Epub 2017 Jan 6.

European Cancer Concord,; University of Leeds,. Electronic address:

In this implementation phase of the European Cancer Patient's Bill of Rights (BoR), we confirm the following three patient-centred principles that underpin this initiative:The right of every European citizen to receive the most accurate information and to be proactively involved in his/her care.The right of every European citizen to optimal and timely access to a diagnosis and to appropriate specialised care, underpinned by research and innovation.The right of every European citizen to receive care in health systems that ensure the best possible cancer prevention, the earliest possible diagnosis of their cancer, improved outcomes, patient rehabilitation, best quality of life and affordable health care. The key aspects of working towards implementing the BoR are:Agree our high-level goal. The vision of 70% long-term survival for patients with cancer in 2035, promoting cancer prevention and cancer control and the associated progress in ensuring good patient experience and quality of life.Establish the major mechanisms to underpin its delivery. (1) The systematic and rigorous sharing of best practice between and across European cancer healthcare systems and (2) the active promotion of Research and Innovation focused on improving outcomes; (3) Improving access to new and established cancer care by sharing best practice in the development, approval, procurement and reimbursement of cancer diagnostic tests and treatments.Work with other organisations to bring into being a Europe based centre that will (1) systematically identify, evaluate and validate and disseminate best practice in cancer management for the different countries and regions and (2) promote Research and Innovation and its translation to maximise its impact to improve outcomes.
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http://dx.doi.org/10.1136/esmoopen-2016-000127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548978PMC
January 2017

Hemolytic Potential of Tafenoquine in Female Volunteers Heterozygous for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency ( Variant) versus G6PD-Normal Volunteers.

Am J Trop Med Hyg 2017 Sep 27;97(3):702-711. Epub 2017 Jul 27.

GlaxoSmithKline Research and Development Ltd., Uxbridge, United Kingdom.

Tafenoquine is an 8-aminoquinoline under investigation for the prevention of relapse in malaria. This open-label, dose-escalation study assessed quantitatively the hemolytic risk with tafenoquine in female healthy volunteers heterozygous for the glucose-6-phosphate dehydrogenase (G6PD)-deficient variant versus G6PD-normal females, and with reference to primaquine. Six G6PD-heterozygous subjects (G6PD enzyme activity 40-60% of normal) and six G6PD-normal subjects per treatment group received single-dose tafenoquine (100, 200, or 300 mg) or primaquine (15 mg × 14 days). All participants had pretreatment hemoglobin levels ≥ 12.0 g/dL. Tafenoquine dose escalation stopped when hemoglobin decreased by ≥ 2.5 g/dL (or hematocrit decline ≥ 7.5%) versus pretreatment values in ≥ 3/6 subjects. A dose-response was evident in G6PD-heterozygous subjects ( = 15) receiving tafenoquine for the maximum decrease in hemoglobin versus pretreatment values. Hemoglobin declines were similar for tafenoquine 300 mg (-2.65 to -2.95 g/dL [ = 3]) and primaquine (-1.25 to -3.0 g/dL [ = 5]). Two further cohorts of G6PD-heterozygous subjects with G6PD enzyme levels 61-80% ( = 2) and > 80% ( = 5) of the site median normal received tafenoquine 200 mg; hemolysis was less pronounced at higher G6PD enzyme activities. Tafenoquine hemolytic potential was dose dependent, and hemolysis was greater in G6PD-heterozygous females with lower G6PD enzyme activity levels. Single-dose tafenoquine 300 mg did not appear to increase the severity of hemolysis versus primaquine 15 mg × 14 days.
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http://dx.doi.org/10.4269/ajtmh.16-0779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590573PMC
September 2017

Glycosylphosphatidylinositol-specific T cells, IFN-γ-producing T cells, and pathogenesis of idiopathic aplastic anemia.

Blood 2017 01 30;129(3):388-392. Epub 2016 Nov 30.

Laboratory of Cancer Genetics and Gene Transfer, Core Research Laboratory-Istituto Toscano Tumori, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.

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http://dx.doi.org/10.1182/blood-2016-09-740845DOI Listing
January 2017