| 1. |
- Astermark, Jan, et al.
(författare)
-
Considerations for shared decision management in previously untreated patients with hemophilia A or B
- 2023
-
Ingår i: Therapeutic advances in hematology. - 2040-6207. ; 14
-
Forskningsöversikt (refereegranskat)abstract
- Recent advances in therapeutics are now providing a wide range of options for adults and children living with hemophilia. Although therapeutic choices are also increasing for the youngest individuals with severe disease, challenges remain about early management decisions, as supporting data are currently limited. Parents and healthcare professionals are tasked with helping children achieve an inclusive quality of life and maintain good joint health into adulthood. Primary prophylaxis is the gold standard to optimize outcomes and is recommended to start before 2 years of age. A range of topics need to be discussed with parents to aid their understanding of the decisions they can make and how these will affect the management of their child/children. For those with a family history of hemophilia, prenatal considerations include the possibility of genetic counseling, prenatal investigations, and planning for delivery, together with monitoring of the mother and neonate, as well as diagnosis of the newborn and treatment of any birth-associated bleeding. Subsequent considerations, which are also applicable to families where infant bleeding has resulted in a new diagnosis of sporadic hemophilia, involve explaining bleed recognition and treatment options, practical aspects of initiating/continuing prophylaxis, dealing with bleeds, and ongoing aspects of treatment, including possible inhibitor development. Over time, optimizing treatment efficacy, in which individualizing therapy around activities can play a role, and long-term considerations, including retaining joint health and tolerance maintenance, become increasingly important. The evolving treatment landscape is creating a need for continually updated guidance. Multidisciplinary teams and peers from patient organizations can help provide relevant information. Easily accessible, multidisciplinary comprehensive care remains a foundation to care. Equipping parents early with the knowledge to facilitate truly informed decision-making will help achieve the best possible longer-term health equity and quality of life for the child and family living with hemophilia. Plain language summary: Points to be taken into account to help families make decisions to best care for children born with hemophilia Medical advances are providing a range of treatment options for adults and children with hemophilia. There is, however, relatively limited information about managing newborns with the condition. Doctors and nurses can help parents to understand the choices for infants born with hemophilia. We describe the various points doctors and nurses should ideally discuss with families to enable informed decision-making. We focus on infants who require early treatment to prevent spontaneous or traumatic bleeding (prophylaxis), which is recommended to start before 2 years of age. Families with a history of hemophilia may benefit from discussions before pregnancy, including how an affected child would be treated to protect against bleeds. When mothers are pregnant, doctors can explain investigations that can provide information about their unborn child, plan for the birth, and monitor mother and baby to minimize bleed risks at delivery. Testing will confirm whether the baby is affected by hemophilia. Not all infants with hemophilia will be born to families with a history of the condition. Identification of hemophilia for the first time in a family (which is ‘sporadic hemophilia’) occurs in previously undiagnosed infants who have bleeds requiring medical advice and possibly hospital treatment. Before any mothers and babies with hemophilia are discharged from hospital, doctors and nurses will explain to parents how to recognize bleeding and available treatment options can be discussed. Over time, ongoing discussions will help parents to make informed treatment decisions: • When and how to start, then continue, prophylaxis. • How to deal with bleeds (reinforcing previous discussions about bleed recognition and treatment) and other ongoing aspects of treatment. ○ For instance, children may develop neutralizing antibodies (inhibitors) to treatment they are receiving, requiring a change to the planned approach. • Ensuring treatment remains effective as their child grows, considering the varied needs and activities of their child.
|
|
| 2. |
- Astermark, Jan, et al.
(författare)
-
Major surgery seems not to influence HIV disease progression in haemophilia patients
- 1998
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048. ; 103:1, s. 10-14
-
Tidskriftsartikel (refereegranskat)abstract
- The influence of major surgery on HIV disease progression and decline in CD4+ cell count was evaluated in 23 seropositive haemophilia patients. 24 HIV-infected patients served as non-operated controls. In addition, 32 age-matched seronegative subjects were included. The follow-up time was up to 5 years. During the course of the study, eight of the operated (35%) and 11 of the non-operated (48%) subjects developed HIV-related symptoms (P=0.267). The relative risk for developing HIV-related symptoms after surgery was 0.60 (95% CI 0.25; 1.48). A significant decline in CD4+ cell counts was observed in both the surgery (4.0 x 10(6)/l/month, 95% CI 2.0; 6.0 x 10(6), P=0.001) and the non-surgery (4.0 x 10(6)/l/month, 95% CI 2.0; 6.0 x 10(6), P=0.004) seropositive subgroup, but no difference between the two subgroups was seen (P=0.793). HIV (6.0 x 10(6)/l/month, 95% CI 2.1; 9.9 x 10(6), P=0.0005) but not surgery (-1.0 x 10(6)/l/ month, 95% CI -3.0; 0.96 x 10(6), P=0.647) was an independent predictor for the decline in CD34+ cell count. No interaction effect was observed between HIV infection and surgery (P=0.361). The annual amount of factor concentrate used for regular replacement therapy did not influence the decline in CD4+ cell count (P=0.492). We conclude that major surgery may be considered in symptom-free HIV-seropositive haemophilia patients, with CD4+ cell counts > or = 0.20 x 10(9)/l under similar premises as for seronegative subjects.
|
|
| 3. |
- Eckhardt, CL, et al.
(författare)
-
Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A
- 2013
-
Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 122:11, s. 1954-1962
-
Tidskriftsartikel (refereegranskat)abstract
- The inhibitor incidence in nonsevere hemophilia A patients with certain F8 mutations approaches the inhibitor incidence in severe patients. These findings are highly relevant for clinical practice, as they facilitate identification of high-risk patients based on F8 genotype.
|
|
| 4. |
- Mollgard, Lars, et al.
(författare)
-
Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities
- 2011
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 96:7, s. 963-971
-
Tidskriftsartikel (refereegranskat)abstract
- Background Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ hybridization for del(5q31). Design and Methods Twenty-eight patients at diagnosis or with relapsed disease and not eligible for standard therapy (16 with acute myeloid leukemia, 12 with intermediate-risk 2 or high-risk myelodysplastic syndrome) were enrolled in this prospective phase II multicenter trial and treated with lenalidomide up to 30 mg daily for 16 weeks. Three patients had isolated del(5q), six had del(5q) plus one additional aberration, 14 had del(5q) and a complex karyotype, four had monosomy 5, and one had del(5q) identified by fluorescence in situ hybridization only. Results Major and minor cytogenetic responses, assessed by fluorescence in situ hybridization, were achieved in 5/26 (19%) and 2/26 (8%) patients, respectively, who received one or more dose of lenalidomide, while two patients achieved only a bone marrow response. Nine of all 26 patients (35%) and nine of the ten who completed the 16 weeks of trial responded to treatment. Using the International Working Group criteria for acute myeloid leukemia and myelodysplastic syndrome the overall response rate in treated patients with acute myeloid leukemia was 20% (3/15), while that for patients with myelodysplastic syndrome was 36% (4/11). Seven patients stopped therapy due to progressive disease and nine because of complications, most of which were disease-related. Response rates were similar in patients with isolated del(5q) and in those with additional aberrations. Interestingly, patients with TP53 mutations responded less well than those without mutations (2/13 versus 5/9, respectively; P = 0.047). No responses were observed among 11 cases with deleterious TP53 mutations. Conclusions Our data support a role for higher doses of lenalidomide in poor prognosis patients with myelodysplastic syndrome and acute myeloid leukemia with deletion 5q. (Clinicaltrials.gov identifier NCT00761449).
|
|
| 5. |
|
|
| 6. |
- Nilsson-Ehle, Herman, et al.
(författare)
-
Quality of life, physical function and MRI T2*in elderly low-risk MDS patients treated to a haemoglobin level of andgt;= 120 g/L with darbepoetin alfa +/- filgrastim or erythrocyte transfusions
- 2011
-
Ingår i: European Journal of Haematology. - : John Wiley and Sons. - 0902-4441 .- 1600-0609. ; 87:3, s. 244-252
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Anaemia in low-risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin +/- granulocyte colony-stimulating factor (G-CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of andgt; 120 g /L. Methods: Thirty-six elderly patients with low-and intermediate-1 risk MDS received darbepoetin (DA) 300 mu g/wk, with the addition of G-CSF if no response. If the Hb target was reached at 16 wk, treatment was maintained until week 26. Remaining patients were transfused to reach the target level for at least 8 wk. Results: Twenty-seven patients completed the study. Response rate to DA +/- G-CSF was 67% in evaluable patients and 56% according to intention to treat. Eighteen patients reached the target Hb level according to protocol. QoL scores for fatigue, dyspnoea, constipation, and physical, role and social functioning improved significantly during study, with similar results for transfused and untransfused patients. Maintaining Hb andgt; 120 g /L did not confer a higher transfusion rate, once the target was reached. In two of fourteen patients, magnetic resonance imaging T2* indicated cardiac iron overload, however, without association with ferritin levels. Conclusions: In elderly anaemic MDS patients, an increment in haemoglobin is associated with improved QoL, whether induced by growth factor treatment or transfusion therapy.
|
|
| 7. |
- Alvarez, Teresa, et al.
(författare)
-
Non-genetic risk factors and their influence on the management of patients in the clinic
- 2015
-
Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 94, s. 2-6
-
Forskningsöversikt (refereegranskat)abstract
- The development of inhibitors is the most serious iatrogenic complication affecting patients with haemophilia. This complication is associated with impaired vital or functional prognosis, reduced quality of life and increased cost of treatment. The reasons why some patients develop antibodies to factor replacement and others do not remain unclear. It is however clear that inhibitor development results from a complex multifactorial interaction between genetic and non-genetic risk factors. Environmental influences implicated in increasing the risk of inhibitor formation can be viewed as modifiable risk factors. Therefore, identification of the non-genetic risk factors may offer the possibility of personalising haemophilia therapy by modifying treatment strategies in high-risk patients in the critical early phase of factor VIII exposure. In this article, we review the non-genetic factors reported as well as the potential impact of danger signals and the different scores for inhibitor development risk stratification.
|
|
| 8. |
- Arvanitakis, Alexandros, et al.
(författare)
-
A comparison of MyPKFiT and WAPPS-Hemo as dosing tools for optimizing prophylaxis in patients with severe haemophilia A treated with Octocog alfa
- 2021
-
Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 27:3, s. 417-424
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: MyPKFiT and the Web-Accessible Population Pharmacokinetic service—Hemophilia (WAPPS-Hemo) are web-based population-based applications developed for helping physicians individualize and optimize replacement therapy. Although MyPKFiT is intended for Octocog alfa and Rurioctocog alfa pegol use only, the WAPPS-Hemo is applicable to all factor VIII concentrates. Aim: To compare MyPKFiT and WAPPS-Hemo as dosing tools for optimizing treatment of patients with severe haemophilia A on regular prophylaxis with Octocog alfa in a real-world setting. Methods: Fourteen patients with severe haemophilia A (median age 30.8 years; range 20–71) were enrolled. The FVIII activity was measured twice after a regular dose of Octocog alfa by the chromogenic and the one-stage assays. PK analyses were performed using each tool and dosing estimations to reach trough levels of 1%, 3% or 5% after 48 h. Findings were calculated and compared. Results: The two PK algorithms yielded similar t½ independent of the type of FVIII assay used. However, there were significant differences in the time to reach 1%, 3% and 5%. The WAPPS-Hemo generated 10–12 h longer time to a trough of 1% and up to 4 h for the troughs of 3% and 5%. Accordingly, the doses estimated by WAPPS-Hemo for a daily regimen were between 28% and 100% of those proposed by MyPKFiT. Conclusions: MyPKFiT and WAPPS-Hemo provided similar half-life estimations for Octocog alfa independent of the FVIII assay used. The doses suggested by WAPPS-Hemo to reach specific troughs were overall lower, which may have implications for treatment optimization.
|
|
| 9. |
- Arvanitakis, Alexandros, et al.
(författare)
-
Clinical outcome and adherence rate in Scandinavian patients with intermediate-intensity prophylaxis before and after the switch of standard half-life FVIII products to BAY 81–8973
- 2022
-
Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 28:2, s. 223-229
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Treatment optimization in haemophilia A can be achieved by choice of FVIII product and knowledge of pharmacokinetics (PK), phenotype and adherence. A favourable PK profile of BAY 81–8973 (octocog alfa) (Kovaltry, Bayer AB) compared to other standard half-life (SHL) FVIII products has been suggested. Aim: To evaluate whether the switch to BAY 81–8973, using the same dosing schedule, impact factor consumption and bleed rates, taking arthropathy and adherence into account. Methods: Forty patients on prophylaxis with SHL (median age 40.5 years) attending the haemophilia treatment centres in Malmö and Oslo were enrolled. The annualised bleeding rate (ABR) and joint bleeding rate (AJBR) before and after the switch to BAY 81–8973 was calculated. PK analyses were performed with WAPPS-Hemo. Joint health status and treatment adherence were assessed. Results: The median ABR and AJBR was 0 before and after the switch, at both centres. The median yearly factor consumption was 3,345 IU/Kg/year in the entire study group corresponding to intermediate-intensity prophylaxis in most patients and with significantly more used in Malmö (3,862 IU/Kg/year), compared to Oslo (2,337 IU/Kg/year) (P.006). There was no correlation between arthropathy and bleeding. The median BAY 81–8973 t½ was 20 h (range 7.5–29 h), with significant correlation to VWF levels, and 13.4 h after exclusion of VWF outliers. Adherence to treatment was 97%. Conclusions: Concentrate switch, using mainly intermediate-intensity regimens with high adherence rates, preserves excellent prophylaxis outcome using standard half-life FVIII products, indicating the value of individualized prophylaxis and close follow-up.
|
|
| 10. |
- Arvanitakis, Alexandros, et al.
(författare)
-
Impact of timing of prophylaxis commencement, F8 genotype and age on factor consumption and health-related quality of life in patients with severe haemophilia A
- 2023
-
Ingår i: Haemophilia. - 1351-8216. ; 29:4, s. 1032-1038
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The timing of prophylaxis and F8 genotype can impact treatment outcomes in adults with severe haemophilia A (HA). Aim: To investigate how F8 genotype, timing, and type of prophylaxis influence arthropathy, bleeding rates, factor consumption and health-related quality of life (HRQoL). Methods: Thirty-eight patients with severe HA were enrolled. Bleeding events were recorded retrospectively during median 12.5 months. F8 gene variants were classified as null or non-null. Joint health and HRQoL were assessed with HJHS and EQ-5D-5L, respectively. Results: The median age at prophylaxis start was 1.25 years in the primary prophylaxis group (N = 15, median age 26 years) and 31.5 years in the secondary group (N = 22, 45 years), respectively. There were significant differences in the medians of HJHS (4 vs. 20, p <.001), EQ-5D-5L index (0.9647 vs. 0.904, p =.022), EQ VAS (87 vs. 75, p =.01) and FVIII consumption (3883 vs. 2737 IU/kg/year, p =.02), between the primary and secondary groups, respectively. Median annualized bleeding rate (ABR) was 0 for both groups. Twenty-five null and thirteen non-null F8 gene variants were identified. In the secondary prophylaxis group, lower median FVIII consumption (1926 vs. 3370 IU/kg/year) was shown for non-null compared to null variants, respectively, with similar ABR and HJHS. Conclusion: Delayed prophylaxis start with intermediate dose intensity prevents bleeds but at a cost of more arthropathy and reduced HRQoL, compared to higher intensity primary prophylaxis. Non-null F8 genotype may allow lower factor consumption with similar HJHS and bleeding rates, compared to null genotype.
|
|
