FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2911822636> ?p ?o ?g. }

• W2911822636 endingPage "S227" @default.
• W2911822636 startingPage "S226" @default.
• W2911822636 abstract "BackgroundAdult dCBT recipients are at significant risk for aGVHD especially involving the GI tract. Investigation of augmented prophylaxis is indicated.MethodsBased on adult donor allograft data (Kennedy et al, Lancet 2015; Drobyski et al Haematologica 2018), we are investigating the addition of a single dose of tocilizumab 8 mg/kg (cap 800mg) on day -1 to standard cyclosporine/ MMF starting day -3 in adult patients (pts) with hematologic malignancies undergoing intermediate intensity Cy 50/ Flu 150/ Thio 10/ TBI 400 dCBT. We report an interim analysis of the first 16 pts of a 27 pt phase II trial (NCT03434730). All pts received standard bacterial/ fungal prophylaxis & Letermovir if CMV seropositive.Results16 pts [median 50 years (range 27-59), median 85 kg (range 59-125), 6 AML, 5 ALL, 2 MPAL, 2 MDS, 1 CML, median aaHCT-CI of 3 (range 0-6)] received double-unit CB grafts with a median CD34+ cell dose of 1.33 × 105/kg/unit (range 0.24-3.83) & median unit-recipient 8-allele HLA-match of 5/8 (range 3-6). Pt outcomes are shown (Table). All (100%) pts engrafted with a median neutrophil recovery of 26 days (range 19-40). 94% of pts engrafted platelets (median 44 days, range 32-59). All pts had single unit dominance (median day 28 blood winning unit chimerism 100% (range 58-100). Prior to engraftment, 11/16 (69%) had no neutropenic fever, 3/16 (19%) pts had fever with bacteremia, 1 pt (6%) had febrile neutropenia (duration 2 days) responding to antibiotics, & 1 pt (6%) had initial fever due to bacteremia followed by fever/ rash attributed to pre-engraftment syndrome (PES). An additional 2 pts developed rash without fever prior to engraftment attributed to PES. Thus, a total of 3/16 (19%) pts had PES (onset ranging 12-14 days). Ten pts developed grade II aGVHD (median onset 45 days, range 26-81) for a cumulative incidence of 63% (95%CI: 33-82). This was limited primarily to skin &/or the upper gut with one pt having stage I lower GI. No pt has developed grade III-IV aGVHD & no pt has had stage II-IV lower GI aGVHD to date (Figure). With a median follow-up of 147 days (range 74-214), 15 pts are alive & disease-free (1 death due to HHV-6 pneumonitis).ConclusionsPreliminary data suggests tocilizumab is safe with no adverse effects upon engraftment or unit dominance. Tocilizumab mitigates PES (expected incidence 65% in dCBT controls, Bhatt et al, ASBMT 2019). Expected days of febrile neutropenia were also reduced especially given the prolonged neutrophil recovery. Notably, lower gut aGVHD appears markedly reduced with no cases of grade III-IV aGVHD or aGVHD mortality to date. Our findings appear consistent with the published adult donor data. Overall, one tocilizumab dose has improved the early post-dCBT morbidity & investigation of this promising & potentially cost-effective approach is ongoing. Adult dCBT recipients are at significant risk for aGVHD especially involving the GI tract. Investigation of augmented prophylaxis is indicated. Based on adult donor allograft data (Kennedy et al, Lancet 2015; Drobyski et al Haematologica 2018), we are investigating the addition of a single dose of tocilizumab 8 mg/kg (cap 800mg) on day -1 to standard cyclosporine/ MMF starting day -3 in adult patients (pts) with hematologic malignancies undergoing intermediate intensity Cy 50/ Flu 150/ Thio 10/ TBI 400 dCBT. We report an interim analysis of the first 16 pts of a 27 pt phase II trial (NCT03434730). All pts received standard bacterial/ fungal prophylaxis & Letermovir if CMV seropositive. 16 pts [median 50 years (range 27-59), median 85 kg (range 59-125), 6 AML, 5 ALL, 2 MPAL, 2 MDS, 1 CML, median aaHCT-CI of 3 (range 0-6)] received double-unit CB grafts with a median CD34+ cell dose of 1.33 × 105/kg/unit (range 0.24-3.83) & median unit-recipient 8-allele HLA-match of 5/8 (range 3-6). Pt outcomes are shown (Table). All (100%) pts engrafted with a median neutrophil recovery of 26 days (range 19-40). 94% of pts engrafted platelets (median 44 days, range 32-59). All pts had single unit dominance (median day 28 blood winning unit chimerism 100% (range 58-100). Prior to engraftment, 11/16 (69%) had no neutropenic fever, 3/16 (19%) pts had fever with bacteremia, 1 pt (6%) had febrile neutropenia (duration 2 days) responding to antibiotics, & 1 pt (6%) had initial fever due to bacteremia followed by fever/ rash attributed to pre-engraftment syndrome (PES). An additional 2 pts developed rash without fever prior to engraftment attributed to PES. Thus, a total of 3/16 (19%) pts had PES (onset ranging 12-14 days). Ten pts developed grade II aGVHD (median onset 45 days, range 26-81) for a cumulative incidence of 63% (95%CI: 33-82). This was limited primarily to skin &/or the upper gut with one pt having stage I lower GI. No pt has developed grade III-IV aGVHD & no pt has had stage II-IV lower GI aGVHD to date (Figure). With a median follow-up of 147 days (range 74-214), 15 pts are alive & disease-free (1 death due to HHV-6 pneumonitis). Preliminary data suggests tocilizumab is safe with no adverse effects upon engraftment or unit dominance. Tocilizumab mitigates PES (expected incidence 65% in dCBT controls, Bhatt et al, ASBMT 2019). Expected days of febrile neutropenia were also reduced especially given the prolonged neutrophil recovery. Notably, lower gut aGVHD appears markedly reduced with no cases of grade III-IV aGVHD or aGVHD mortality to date. Our findings appear consistent with the published adult donor data. Overall, one tocilizumab dose has improved the early post-dCBT morbidity & investigation of this promising & potentially cost-effective approach is ongoing." @default.
• W2911822636 created "2019-02-21" @default.
• W2911822636 creator A5000759396 @default.
• W2911822636 creator A5000852934 @default.
• W2911822636 creator A5002993817 @default.
• W2911822636 creator A5003197311 @default.
• W2911822636 creator A5003831049 @default.
• W2911822636 creator A5016160764 @default.
• W2911822636 creator A5035685537 @default.
• W2911822636 creator A5043510888 @default.
• W2911822636 creator A5044552886 @default.
• W2911822636 creator A5058746837 @default.
• W2911822636 creator A5066163702 @default.
• W2911822636 creator A5069648775 @default.
• W2911822636 creator A5070096873 @default.
• W2911822636 creator A5085550690 @default.
• W2911822636 date "2019-03-01" @default.
• W2911822636 modified "2023-10-18" @default.
• W2911822636 title "Addition of Tocilizumab to Cyclosporine/ MMF for Acute Graft-Vs-Host Disease (aGVHD) Prophylaxis in Adult Double Unit Cord Blood Transplant (dCBT) Recipients: Promising Preliminary Results of a Phase II Clinical Trial." @default.
• W2911822636 doi "https://doi.org/10.1016/j.bbmt.2018.12.216" @default.
• W2911822636 hasPublicationYear "2019" @default.
• W2911822636 type Work @default.
• W2911822636 sameAs 2911822636 @default.
• W2911822636 citedByCount "0" @default.
• W2911822636 crossrefType "journal-article" @default.
• W2911822636 hasAuthorship W2911822636A5000759396 @default.
• W2911822636 hasAuthorship W2911822636A5000852934 @default.
• W2911822636 hasAuthorship W2911822636A5002993817 @default.
• W2911822636 hasAuthorship W2911822636A5003197311 @default.
• W2911822636 hasAuthorship W2911822636A5003831049 @default.
• W2911822636 hasAuthorship W2911822636A5016160764 @default.
• W2911822636 hasAuthorship W2911822636A5035685537 @default.
• W2911822636 hasAuthorship W2911822636A5043510888 @default.
• W2911822636 hasAuthorship W2911822636A5044552886 @default.
• W2911822636 hasAuthorship W2911822636A5058746837 @default.
• W2911822636 hasAuthorship W2911822636A5066163702 @default.
• W2911822636 hasAuthorship W2911822636A5069648775 @default.
• W2911822636 hasAuthorship W2911822636A5070096873 @default.
• W2911822636 hasAuthorship W2911822636A5085550690 @default.
• W2911822636 hasBestOaLocation W29118226361 @default.
• W2911822636 hasConcept C126322002 @default.
• W2911822636 hasConcept C141071460 @default.
• W2911822636 hasConcept C2777063308 @default.
• W2911822636 hasConcept C29730261 @default.
• W2911822636 hasConcept C71924100 @default.
• W2911822636 hasConcept C74133956 @default.
• W2911822636 hasConcept C90924648 @default.
• W2911822636 hasConceptScore W2911822636C126322002 @default.
• W2911822636 hasConceptScore W2911822636C141071460 @default.
• W2911822636 hasConceptScore W2911822636C2777063308 @default.
• W2911822636 hasConceptScore W2911822636C29730261 @default.
• W2911822636 hasConceptScore W2911822636C71924100 @default.
• W2911822636 hasConceptScore W2911822636C74133956 @default.
• W2911822636 hasConceptScore W2911822636C90924648 @default.
• W2911822636 hasIssue "3" @default.
• W2911822636 hasLocation W29118226361 @default.
• W2911822636 hasOpenAccess W2911822636 @default.
• W2911822636 hasPrimaryLocation W29118226361 @default.
• W2911822636 hasRelatedWork W2002120878 @default.
• W2911822636 hasRelatedWork W2003938723 @default.
• W2911822636 hasRelatedWork W2047967234 @default.
• W2911822636 hasRelatedWork W2095822339 @default.
• W2911822636 hasRelatedWork W2118496982 @default.
• W2911822636 hasRelatedWork W2364998975 @default.
• W2911822636 hasRelatedWork W2439875401 @default.
• W2911822636 hasRelatedWork W4238867864 @default.
• W2911822636 hasRelatedWork W2519357708 @default.
• W2911822636 hasRelatedWork W2525756941 @default.
• W2911822636 hasVolume "25" @default.
• W2911822636 isParatext "false" @default.
• W2911822636 isRetracted "false" @default.
• W2911822636 magId "2911822636" @default.
• W2911822636 workType "article" @default.