CLINICAL NEWS
Haplo-HCT From Older Donors Associated With Worse Outcomes in Acute Leukemias
The use of haploidentical ( haplo ) related donors has made it possible for patients with leukemia who lack a human leukocyte antigen ( HLA )– matched donor to receive a hematopoietic cell transplantation ( HCT ). But , because several haplo relative donors are typically available for any given patient , choosing the “ best ” donor for a patient is complicated .
According to a retrospective study presented at the 2017 ASH Annual Meeting , older donor age appears to lead to worse post-HCT survival outcomes , including higher nonrelapse mortality ( NRM ) and shorter overall survival ( OS ). Patients who received transplants from their adult children ( older than 35 years ) also had worse outcomes , reported lead author Jonathan Canaani , MD , of the Hematology Division at the Sheba Medical Center in Givatayim , Israel .
Researchers retrospectively analyzed the multinational registry of the European Society for Blood and Marrow Transplantation ’ s Acute Leukemia Working Party to identify patients with acute myeloid leukemia ( AML ) or acute lymphocytic leukemia ( ALL ) who underwent a first haplo-HCT between 2005 and 2015 . Of the 1,270 patients included , 1,019 had AML and 251 had ALL . Most patients ( n = 700 ) were 40 years or older when they received haplo-HCT , and the remaining 570 patients were younger than 40 .
After a median follow-up of 27 months ( range = 0.6-119 months ), results from multivariate analyses revealed that , among patients older than 40 years , outcomes were worse when donors were older than 40 years , compared with donors younger than 40 . In addition to higher NRM ( hazard ratio [ HR ] = 1.86 ; 95 % CI 1.18-2.94 ; p = 0.007 ), older donor age was associated with inferior :
• leukemia-free survival ( LFS ): HR = 1.59 ( 95 % CI 1.13-2.24 ; p = 0.007 )
• OS : HR = 1.74 ( 95 % CI 1.22-2.47 ; p = 0.002 )
• graft-versus-host-disease ( GVHD )– free or relapse-free survival ( GRFS ): HR = 1.6 ( 95 % CI 1.16-2.22 ; p = 0.004 )
Donor relationship to patients ( sibling vs . child donor ) did not statistically significantly impact outcomes , the researchers reported . However , in the group of patients over 40 years who received transplants from their
ASHClinicalNews . org children , outcomes were less favorable when donors were over the age of 35 . These recipients experienced an increased rate of NRM ( HR = 1.82 ; 95 % CI 1.13- 2.9 ; p = 0.01 ), inferior LFS ( HR = 1.5 ; 95 % CI 1.05-2.13 ; p = 0.03 ), and inferior OS
VONVENDI [ von Willebrand factor ( Recombinant )] IS A PURIFIED RECOMBINANT VON WILLEBRAND FACTOR WITH AN OPTION TO DOSE INDEPENDENTLY OF RECOMBINANT FACTOR VIII ACCORDING TO PATIENT NEED . 1
For each bleeding episode , administer the first dose of VONVENDI with an approved recombinant ( non-von Willebrand factor-containing ) factor VIII ( rFVIII ) if factor VIII baseline levels are < 40 % or are unknown . VONVENDI can be administered without rFVIII in some patients if FVIII levels are ≥40 % normal activity ( 0.4 IU / mL ), if an urgent increase is not needed or if the baseline FVIII : C level is sufficient to ensure hemostasis . 1 Comprehensive dosing information can be found in the VONVENDI full Prescribing Information .
VONVENDI [ von Willebrand factor ( Recombinant )] Important Information
INDICATION
VONVENDI TM [ von Willebrand factor ( Recombinant )] is a recombinant von Willebrand factor indicated for on-demand treatment and control of bleeding episodes in adults ( age 18 and older ) diagnosed with von Willebrand disease .
Detailed Important Risk Information
CONTRAINDICATIONS
( HR = 1.5 ; 95 % CI 1.04-2.15 ; p = 0.03 ), compared with recipients who had younger donors .
The effect of donor age was less straightforward in younger recipients (< 40 years ). In this group , having a donor older
VONVENDI is contraindicated in patients who have had life-threatening hypersensitivity reactions to VONVENDI or constituents of the product ( tri-sodium citrate-dihydrate , glycine , mannitol , trehalose-dihydrate , polysorbate 80 , and hamster or mouse proteins ).
WARNINGS AND PRECAUTIONS Embolism and Thrombosis
Thromboembolic reactions , including disseminated intravascular coagulation ( DIC ), venous thrombosis , pulmonary embolism , myocardial infarction , and stroke , can occur , particularly in patients with known risk factors for thrombosis . Monitor for early signs and symptoms of thrombosis such as pain , swelling , discoloration , dyspnea , cough , hemoptysis , and syncope .
In patients requiring frequent doses of VONVENDI with recombinant factor VIII , monitor plasma levels for FVIII : C activity because an excessive rise in factor VIII levels can increase the risk of thromboembolic complications .
Hypersensitivity Reactions
Hypersensitivity reactions , including anaphylaxis , may occur . Symptoms can include anaphylactic shock , generalized urticaria , angioedema , chest tightness , hypotension , shock , lethargy , nausea , vomiting , paresthesia , pruritus , restlessness , wheezing and / or acute respiratory distress . If signs and symptoms of severe allergic reactions occur , immediately discontinue administration of VONVENDI and provide appropriate supportive care .
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VONVENDI ®
[ von Willebrand factor ( Recombinant )] IS IN YOUR CORNER
Neutralizing Antibodies
Neutralizing antibodies ( inhibitors ) to von Willebrand factor and / or factor VIII can occur . If the expected plasma levels of VWF activity ( VWF : RCo ) are not attained , perform an appropriate assay to determine if anti-VWF or anti-FVIII inhibitors are present . Consider other therapeutic options and direct the patient to a physician with experience in the care of either von Willebrand disease or hemophilia A .
In patients with high levels of inhibitors to VWF or factor VIII , VONVENDI therapy may not be effective and infusion of this protein may lead to severe hypersensitivity reactions . Since inhibitor antibodies can occur concomitantly with anaphylactic reactions , evaluate patients experiencing an anaphylactic reaction for the presence of inhibitors .
ADVERSE REACTIONS
The most common adverse reaction observed in ≥2 % of subjects in clinical trials ( n = 66 ) was generalized pruritus .
Please see VONVENDI Brief Summary on the following page .
VONVENDIPRO . COM
than 55 years was independently associated with a lower risk for extensive chronic GVHD ( HR = 0.16 ; 95 % CI 0.02-0.95 ; p = 0.044 ), but an increased risk of relapse ( HR = 1.85 ; 95 % CI 0.97-3.49 ; p = 0.058 ). The rates of NRM , OS , LFS , acute GVHD , and GRFS were not statistically significantly impacted by donor age in those younger than 40 years .
“ Our data establish donor age and kinship as significant determinants of outcome
THE FIRST AND ONLY RECOMBINANT VON WILLEBRAND FACTOR
Reference : 1 . VONVENDI [ von Willebrand factor ( Recombinant )] Prescribing Information .