Clofarabine and Busulfan Myeloablative Conditioning in Allogeneic Hematopoietic Cell Transplantation for Patients With Active Myeloid Malignancies.

Patients with refractory or relapsed and refractory myeloid malignancies have a poor prognosis. Allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning (MAC) in patients with active, chemotherapy-refractory myeloid disease is historically associated with high rates of relapse and nonrelapse mortality (NRM). A MAC regimen combining clofarabine with busulfan (Clo/Bu4) has been reported to exhibit antileukemic activity with acceptable toxicity in patients age ≤70 years. Here we describe the clinical outcomes of a real-world population of patients with active myeloid malignancies undergoing allogeneic HCT with Clo/Bu4 MAC. In a single-center retrospective descriptive analysis, we identified patients who underwent HCT for myeloid malignancies not in remission using Clo/Bu4 MAC between 2012 and 2020. We report event-free survival (EFS) and overall survival (OS), cumulative incidences of relapse and NRM, and the incidence and severity of acute and chronic graft-versus-host disease (GVHD). We identified 69 patients with a median age of 60 years (range, 22 to 70 years). Most patients had relapsed/refractory or primary refractory acute myelogenous leukemia (AML; n = 55) or refractory myelodysplastic syndrome (MDS; n = 12); 1 patient had chronic myelogenous leukemia, and 1 patient had a blastic plasmacytoid dendritic cell neoplasm. Fifty patients (72.5%) had complete remission at day 100 post-transplantation. Two-year EFS and OS were 30% (95% confidence interval [CI], 20% to 44%) and 40% (95% CI, 29% to 54%), respectively. Patients with AML had a 2-year EFS and OS of 28% (95% CI, 18% to 44%) and 38% (95% CI, 27% to 54%), respectively; those with MDS had a 2-year EFS and OS of 47% (95% CI, 25% to 88%) and 56% (95% CI, 33% to 94%), respectively. The cumulative incidence of relapse at 2 years was 39% (95% CI, 27% to 51%) for all patients, including 45% (95% CI, 31% to 58%) in the patients with AML and 18% (95% CI, 2% to 45%) in those with MDS. NRM at 2 years was 31% (95% CI, 20% to 42%), including 27% (95% CI, 15% to 39%) in patients with AML and 35% (95% CI, 10% to 63%) in those with MDS. The total incidence of acute GVHD (aGVHD) of any severity was 80%, and the incidence of grade III-IV aGVHD was 22%. In patients who achieved remission, those who required systemic immunosuppression for aGVHD (58%) had poorer 2-year EFS (29% versus 54%; P = .05) and 2-year OS (39% versus 70%; P = .04) compared to those who did not. The 2-year cumulative incidence of chronic GVHD was 44% (95% CI, 28% to 58%). Clo/Bu4 MAC followed by allogeneic HCT for patients with active myeloid malignancies is an effective transplantation strategy for patients up to age 70, particularly those with advanced MDS. The high incidence of and poor outcomes associated with aGVHD highlight the importance of optimizing preventative strategies.

CAR T in adult ALL: When and for whom?

Chimeric antigen receptor T cell therapy targeting CD19 (CART19) has shown remarkable results in patients with relapsed/refractory (r/r) B cell acute lymphoblastic leukemia (ALL). In patients 25 years of age or younger CART19 therapy is an accepted standard of care, while the treatment of older adults is less straight forward and possible only in the context of a clinical trial. Treatment of older patients with CAR T cells requires careful consideration of overall treatment goals, suitability of a consolidative hematopoietic stem cell transplant (HSCT), alternative treatment options, patient risk profile, and anticipated responses and toxicities of the specific CAR T cell products available. Here we use patient guided examples to inform approaches to care.

Effect of high-dose vocal fold injection of cidofovir and bevacizumab in a porcine model.

OBJECTIVES: Perform a follow-up study to investigate the histologic impact of high-dose intralaryngeal cidofovir injections in porcine vocal cords, either alone or in combination with bevacizumab, and compared to saline controls. STUDY DESIGN: This was an in vivo study involving 24 pigs with blinded pathologist review of specimens. Six groups were created, with four subjects in each group. Each subject received 10 or 20 mg of either cidofovir or bevacizumab alone, or in combination, injected into the right vocal cord. The left vocal fold was used as a saline control. Three separate injections were made at 2-week intervals. Larynges were harvested at 8 and 12 weeks, stained with hematoxylin and eosin and trichrome stain, and reviewed for histologic changes by two blinded pathologists. RESULTS: Minimal inflammation, edema, and atypia were noted with all treatments. Increased glandular inflammation was noted with 10 mg bevacizumab (P < 0.05), which decreased when combined with 10 mg cidofovir (P < 0.05). No lamina propria or muscle fibrosis was observed. Drug duration had no statistically significant histologic impact. CONCLUSION: High-dose cidofovir and bevacizumab do not induce detrimental vocal fold changes. Combination cidofovir and bevacizumab do not cause vocal fold scarring. Further work is needed to assess systemic concentration with this high-dose combination in humans. LEVEL OF EVIDENCE: N/A. Laryngoscope, 127:671-675, 2017.

Maxillary myxoma: A case report and review.

An odontogenic myxoma is a rare, benign tumor that is found almost exclusively in the facial bones, usually the mandible. The diagnosis poses a challenge because its features overlap with those of other benign and malignant neoplasms. We present an unusual case of odontogenic myxoma that involved the maxilla, and we review the clinical, radiographic, and histologic characteristics of this case. Even though it is benign, odontogenic myxoma can be locally invasive and cause significant morbidity. Complete surgical excision is the treatment of choice, but it can be challenging because of the tumor's indistinct margins.

The pediatric sedation unit: a prospective analysis of parental satisfaction.

UNLABELLED: As financial pressures drive health care to be more cost-effective and efficient, performing procedures outside the main operating room (MOR) is becoming more common. Pediatric sedation units (PSU) have proven both effective and safe at providing anesthesia for children. However, there is limited data available regarding the PSU and its potential application in pediatric otolaryngology. OBJECTIVE: To evaluate the experience of performing pediatric outpatient procedures in a PSU through a parental satisfaction survey. METHODS: Pediatric otolaryngology procedures performed in the PSU were prospectively recorded in a database. A prospective survey analysis was performed that measured parental satisfaction with scheduling/registration for surgery, nursing care, surgeon care, facility environment, timing/duration, and overall satisfaction. Parents completed this survey for outpatient procedures performed in either the PSU or in the MOR. The same attending surgeon was involved in all cases, with the only independent variable being the location of the surgery. Fifty surveys were collected for each group, and the surveys scores were statistically compared using nonparametric statistical analysis. RESULTS: Parental satisfaction was high in both the PSU and OR, with mean overall satisfaction scores of 4.8 and 4.9 (respectively) on an ordinal scale from 1 to 5. Parents reported greater clarity in preoperative information in the MOR (mean 4.8) compared to the PSU (mean 4.6) (p<0.006). Also, parents reported that MOR procedures started on time more often than those in the PSU (90-64%, p<0.002). There were no significant differences between locations in any other survey metrics, with mean satisfaction scores ranging from 4.5 to 5.0. CONCLUSIONS: The PSU is a satisfactory patient experience for outpatient procedures in pediatric otolaryngology at our institution. However, this parent survey has identified education prior to surgery and timeliness of surgery as two areas to improve to meet the satisfaction standard provided by the OR.

Effect of vocal fold injection of cidofovir and bevacizumab in a porcine model.

IMPORTANCE: Recurrent respiratory papillomatosis (RRP) is a common and often chronic disorder. Intralaryngeal bevacizumab has gained recent interest as an adjuvant therapy for RRP. However, no histologic model has been published describing the effects of bevacizumab on the vocal fold. OBJECTIVE: To investigate the histologic effects of bevacizumab injections into the vocal fold and compare these findings with those for cidofovir and saline control injections. DESIGN AND SETTING: In vivo animal study involving eighteen 1-year-old Yorkshire crossbreed pigs, with a blinded review of pathologic findings conducted in a veterinary research laboratory. INTERVENTIONS: The pigs were randomly divided into six study groups receiving 2.5 or 5.0 mg of cidofovir or bevacizumab alone or in combination. Each pig received an injection of 0.5 mL of the test drug in the right vocal fold and 0.5 mL of saline in the left vocal fold. These injections were performed 4 times during the course of 8 weeks. One pig from each group was killed humanely and the larynges harvested 2 weeks after the last injection. The remaining pigs were killed 4 months after the last injection on the remaining pigs. The vocal folds were fixed and stained with hematoxylin-eosin and trichrome and reviewed for histologic changes by 3 blinded pathologists. MAIN OUTCOMES AND MEASURES: Histologic changes to the vocal folds. RESULTS: Minimal inflammation, edema, and atypia were found in all treatment groups. No appreciable histologic differences were found among the 3 treatment groups and their controls. No difference was seen in the vocal folds that were harvested late (4 months) vs early (2 weeks) after last injection. No fibrosis was found in any of the specimens. CONCLUSIONS AND RELEVANCE: No histologic evidence suggests that intralaryngeal cidofovir or bevacizumab alone or in combination resulted in significant changes to the porcine vocal fold. Future studies may build on this model to test higher dosages and/or may combine injections with potassium titanyl phosphate laser therapy.

IMOUTA: a proposal for patient care handoffs.

OBJECTIVES/HYPOTHESIS: An increased frequency of patient handoffs has occurred as a result of the new resident work-hour restrictions that have recently been instituted. Inadequate handoff of patient care has been associated with adverse patient events due to residents being unprepared for events that happen during cross cover periods. The objective of our study was to develop and test the effectiveness of a patient handoff method in an otolaryngology residency program. STUDY DESIGN: Single-blinded controlled clinical trial. METHODS: A standardized, anonymous questionnaire was developed that scored on-call residents' understanding of their patients' diagnoses, hospital courses, active concerns, and treatment plans. For the first 45 days, residents used their traditional handoff. This handoff was prepared by the residents, relaying relevant patient information without any structured format. For the next 45 days, the residents followed the acronym of IMOUTA for handoffs. This mnemonic was developed to help residents identify data (I), medical course (M), outcomes possible tonight (OU), responsibilities to do tonight (T), and opportunity to ask questions and give morning feedback in the AM (A). The questionnaires were then compared at the end of the study. RESULTS: The residents who used the IMOUTA acronym scored significantly higher on their perceived knowledge of patients diagnoses (P = 0.001), hospital courses (P <0.001), active concerns (P <0.001), and treatment plans (P <0.001). CONCLUSION: Residents felt significantly better prepared for call duties when using the IMOUTA acronym. This standardized system of patient handoff may also be valuable to other residency programs.

Total airway reconstruction.

We present a case of obstructive sleep apnea (OSA) that required multilevel surgical correction of the airway and literature review and discuss the role supraglottic laryngeal collapse can have in OSA. A 34-year-old man presented to a tertiary otolaryngology clinic for treatment of OSA. He previously had nasal and palate surgeries and a Repose tongue suspension. His residual apnea hypopnea index (AHI) was 67. He had a dysphonia associated with a true vocal cord paralysis following resection of a benign neck mass in childhood. He also complained of inspiratory stridor with exercise and intolerance to continuous positive airway pressure. Physical examination revealed craniofacial hypoplasia, full base of tongue, and residual nasal airway obstruction. On laryngoscopy, the paretic aryepiglottic fold arytenoid complex prolapsed into the laryngeal inlet with each breath. This was more pronounced with greater respiratory effort. Surgical correction required a series of operations including awake tracheostomy, supraglottoplasty, midline glossectomy, genial tubercle advancement, maxillomandibular advancement, and reconstructive rhinoplasty. His final AHI was 1.9. Our patient's supraglottic laryngeal collapse constituted an area of obstruction not typically evaluated in OSA surgery. In conjunction with treating nasal, palatal, and hypopharyngeal subsites, our patient's supraglottoplasty represented a key component of his success. This case illustrates the need to evaluate the entire upper airway in a complicated case of OSA.

Noma in an Afghani child: a case report.

We present a case of Cancrum Oris, also known as Noma, in a child treated by an Otorhinolaryngologist at a United States-led Joint Forces hospital in Afghanistan. Noma is a deadly, necrotizing infection of the face that is rarely seen in wealthy nations but can cause significant morbidity in third world countries. Through a literature review, we report the incidence, risk factors, clinical features, and proposed treatment for this disease.