Management of people with haemophilia A undergoing surgery while receiving emicizumab prophylaxis: Real-world experience from a large comprehensive treatment centre in the US.

INTRODUCTION: Surgery is frequently required in persons with haemophilia A (PwHA). Emicizumab, a bispecific, humanized monoclonal antibody, bridges activated factor (F) IX and FX. Management of patients undergoing surgery while receiving emicizumab is of clinical interest due to paucity of data. AIM: Review real-world experience of PwHA with/without FVIII inhibitors who required surgery while receiving emicizumab prophylaxis. METHODS: Data regarding peri-operative management, including type of surgery, haemostatic agent use and bleeding complications, were collected for PwHA receiving emicizumab undergoing surgery between 25/10/18 and 31/12/19 at the Indiana Hemophilia and Thrombosis Center. Analyses were exploratory and descriptive. RESULTS: Twenty minor and five major surgeries were performed in 17 and five patients, respectively. Overall, 9/20 minor surgeries were planned to occur with emicizumab as the sole haemostatic agent; of these, four required additional coagulation factor (2 due to haematomas following port removals, 1 due to oozing at port removal site, 1 due to bleeding following squamous cell carcinoma removal). Three of the 11 minor surgeries with planned additional coagulation factor resulted in non-major bleeds; all were safely managed with additional coagulation factor. All five major surgeries were planned with additional haemostatic agents; there was 1 bleed in a patient undergoing elbow synovectomy with nerve transposition, likely triggered by physical/occupational therapy. There were no major bleeds, thrombotic events or deaths. CONCLUSIONS: Additional haemostatic agent use is safe in PwHA undergoing surgery while receiving emicizumab. Additional data are needed to determine the optimal dosing/length of treatment of additional haemostatic agents to lower bleeding risk.

Myeloablative, but not Reduced-Intensity, Conditioning Overcomes the Negative Effect of Flow-Cytometric Evidence of Leukemia in Acute Myeloid Leukemia.

Stringent complete remission (CR) in acute myeloid leukemia (AML) requires the absence of both morphologic and flow cytometric evidence of disease. We have previously shown that persistent AML detected by flow cytometry (FC+) before reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT) was associated with significantly increased relapse, shorter disease-free survival (DFS), and poorer overall survival (OS), independent of morphologic blast count. We evaluated the effect of FC status on outcomes of alloHCT for AML after either myeloablative conditioning (MAC) or RIC regimens in 203 patients (MAC, n = 80, and RIC, n = 123) with no morphologic evidence of persistent AML pretransplant on marrow biopsy. The allografts included 130 umbilical cord blood (UCB) and 73 sibling donors. We performed central review of pretransplant standard sensitivity FC to identify detectable FC+. Twenty-five patients were FC+, including 15 (18.7%) receiving MAC and 10 (8.1%) RIC alloHCT. Among RIC patients FC+ was associated with significantly inferior relapse, DFS, and OS (multiple regression HR, 3.8; 95% CI, 1.7 to 8.7; P < .01 for relapse; HR, 2.9; 95% CI, 1.4 to 5.9; P < .01 for DFS; and HR, 3.4; 95% CI, 1.7 to 7; P < .01 for OS). In contrast, FC+ status was not associated with relapse or decreased OS after MAC. These data suggest that MAC, but not RIC, overcomes the negative effect of pretransplant FC+ after sibling or UCB alloHCT. Therefore, a deeper pretransplant leukemia-free state is preferred for those treated with RIC.

The impact of Agent Orange exposure on prognosis and management in patients with chronic lymphocytic leukemia: a National Veteran Affairs Tumor Registry Study.

Exposure to Agent Orange (AO) has been associated with the development of chronic lymphocytic leukemia (CLL). We performed a retrospective study of 2052 Vietnam veterans identified in the National VA Tumor Registry to assess the impact of AO exposure on CLL prognosis, treatment and survival. Prognostic factors did not differ based on exposure. Veterans exposed to AO were diagnosed younger (63.2 vs. 70.5 years, p < .0001) and had longer overall survival (median not reached vs. 91 months, p < .001). This prolonged survival was in the subgroups of patients aged 60-69 years (p< .0001) and those with 11q deletion (p < .0001). Those exposed to AO were more likely to be treated with fludarabine, chlorambucil and rituximab (38 vs. 21%, p < .001) and bendamustine plus rituximab (25 vs. 18%, p = 0.039) as first line therapy. Exposure to AO was not associated with either poor prognostic factors or shortened overall survival in our large veteran population with CLL.

Axillary lymph node coverage with 3-dimensional tangential field irradiation and correlation with heart and lung dose.

PURPOSE: The American College of Surgeons Oncology Group Z0011 trial indicated no benefit from axillary lymph node (LN) dissection after a positive sentinel LN biopsy in patients receiving breast irradiation, suggesting that level I-II LNs were covered in tangential fields. METHODS AND MATERIALS: We evaluated 50 computed tomography-based tangential breast plans and contoured level I-III axillary LNs using the Radiation Therapy Oncology Group guidelines. The volumes of level I-III LN regions covered by 90% and 95% of the prescription dose (PD) were calculated and correlated with the V20 ipsilateral lung and mean heart dose. We calculated field length, distance from the humeral head, and separation. The Pearson correlation method and linear models were used in the correlative study. RESULTS: Level I LN mean and median volume (MMV) covered by 90% of the PD were 46.8% and 47.2%, respectively. MMV covered by 95% of the PD was 30.8% and 29.62%. Mean and median dose to level I LNs were 29.03 Gy and 30.13 Gy, respectively. The MMV of level II LNs covered by 90% of the PD was 2.49% and 0%. The mean and median dose to level II LNs were 6.09 Gy and 2.12 Gy, respectively. The MMV of level III LNs was 0% with a mean and median dose of 1.04 Gy and 0.92 Gy, respectively. There was a moderate correlation between the 95% prescription coverage of level I LNs and V20 ipsilateral lung and a smaller correlation between 95% prescription coverage of level I LNs and mean heart dose. Distance from the humeral head was inversely correlated with coverage of level I and II LNs and positively correlated with V20 lung. CONCLUSION: In most patients, <50% of the level I LN volume was covered by 90% of the PD and <30% was covered by 95%; <5% of the level II nodes were covered by 90% of the PD; and coverage was 0% for level III LNs.