HLA-haploidentical hematopoietic stem cells transplantation with regulatory and conventional T-cell adoptive immunotherapy in pediatric patients with very high-risk acute leukemia.

Allogeneic hematopoietic stem cell transplantation (HSCT) is still needed for many children with very high-risk acute leukemia. An HLA-haploidentical family donor is a suitable option for those without an HLA-matched donor. Here we present outcomes of a novel HLA-haploidentical HSCT (haplo-HSCT) strategy with adoptive immunotherapy with thymic-derived CD4+CD25+ FoxP3+ regulatory T cells (Tregs) and conventional T cells (Tcons) performed between January 2017 and July 2021 in 20 children with high-risk leukemia. Median age was 14.5 years (range, 4-21), 15 had acute lymphoblastic leukemia, 5 acute myeloid leukemia. The conditioning regimen included total body irradiation (TBI), thiotepa, fludarabine, cyclophosphamide. Grafts contained a megadose of CD34+ cells (mean 12.4 × 106/Kg), Tregs (2 × 106/Kg) and Tcons (0.5-1 × 106/Kg). All patients achieved primary, sustained full-donor engraftment. Only one patient relapsed (5%). The incidence of non-relapse mortality was 15% (3/20 patients). Five/20 patients developed ≥ grade 2 acute Graft versus Host Disease (aGvHD). It resolved in 4 who are alive and disease-free; 1 patient developed chronic GvHD (cGvHD). The probability of GRFS was 60 ± 0.5% (95% CI: 2.1-4.2) (Fig. 6), CRFS was 79 ± 0.9% (95% CI: 3.2-4.9) as 16/20 patients are alive and leukemia-free. The median follow-up was 2.1 years (range 0.5 months-5.1 years). This innovative approach was associated with very promising outcomes of HSCT strategy in pediatric patients.

MicroRNA expression is associated with human papillomavirus status and prognosis in mucosal head and neck squamous cell carcinomas.

OBJECTIVES: The major cause of mucosal squamous cell carcinomas of the head and neck (HNSCCs) has been attributed to human papillomavirus (HPV) infection. Here we investigate if microRNA expression in HNSCC can be used as a prognostic tool with or without HPV status. MATERIALS AND METHODS: We performed a discovery miRNA microarray (miRBase v.21) profiling of 52 tonsillar SCCs with TaqMan real-time PCR validation of 228 HNSCCs. Patients had a histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx or larynx. Logistic regression models were used to estimate the magnitude of the effect of association with clinical factors and miRNAs associated with HPV status. For recurrence and survival analysis, we used unadjusted and multivariable adjusted Cox proportional hazard regression models. RESULTS: Seventeen miRNAs were significantly associated with better prognosis in the discovery phase and were validated in the extended dataset. The best fitting model (AUC = 0.92) for HPV status included age, smoking, and miRNAs: miR-15b, miR-20b, miR-29a, miR-29c, miR-142, miR-146a and miR-205. Using Cox regression model for recurrence, miR-29a was associated with 49% increased risk of recurrence while miR-30e and miR-342 were associated with decreased risk of recurrence with HRs 0.92 (95% CI 0.85-0.99) and 0.84 (95% CI 0.73-0.98), respectively. Our best fitting model for survival included age, gender, alcohol consumption, N stage, recurrence, HPV status, together with miRNAs-20b, 29a, and 342. CONCLUSION: miRNAs show potential to serve as usual biomarkers to predict the clinical course of patients with mucosal HNSCC.

A phase 1, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC).

BACKGROUND: We conducted a phase 1 dose escalation study (ACTRN12618000140257 registered on 30/01/2018) to evaluate the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) in subjects previously treated for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Eligible subjects had to have no evidence of recurrent and/or metastatic disease at least 12 weeks following the completion of treatment. Three dosing cohorts each consisted of four subjects: group 1: 0.25 mg/dose, group 2: 1 mg/dose, group 3: 4 mg/dose. AMV002 was delivered intradermally on days 0, 28 and 56. Incidence and severity of treatment-emergent adverse events (TEAE) including local reaction at the injection site, and vaccination compliance were recorded. T cell and antibody responses to HPV16 E6 and E7 were measured by interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay and enzyme-linked immunosorbent assay (ELISA). RESULTS: All subjects completed the vaccination programme and experienced mild discomfort at the injection site(s). Pre-immunisation, cell-mediated responses to HPV16 E6 and E7 were evident in all subjects, and E7-specific antibodies were detected in 11 (91.7%), reflecting previous exposure to HPV. Post-vaccination, 10 of 12 (83.3%) subjects responded to one or more of the E6 and/or E7 peptide pools, while 2 (16.7%) did not show additional vaccine-induced cell-mediated responses. Vaccination resulted in a ≥ 4-fold increase in anti-HPV16 E7 antibody titre in one subject in group 3. CONCLUSIONS: AMV002 was well tolerated at all dose levels and resulted in enhanced specific immunity to virus-derived tumour-associated antigens in subjects previously treated for HPV-associated OPSCC.

Management of advanced adenoid cystic carcinoma infiltrating the skull base: a contemporary review.

INTRODUCTION: This article provides an overview of the natural history and management of adenoid cystic carcinoma infiltrating the skull base (SB ACC). METHODS: A comprehensive review of the available literature and discussion regarding the current management of SB ACC. RESULTS: This review describes the unique pathology, appropriate diagnostic work-up and contemporary management options in SB ACC. There is a specific focus on the role of surgical resection with post-operative radiotherapy, given the literature suggesting a superior locoregional control rate. The importance of surgical decision making and varying surgical approaches are detailed. In addition, the emerging role of biological agents is discussed. CONCLUSION: The gold standard for SB ACC is surgical resection and post-operative radiation, given the superior locoregional control. In patients not amendable to surgery, palliative radiation should be considered. The role of biological agents is still evolving. The complexity of SB ACC management mandates experienced multi-speciality management.

Co-Phenylcaine Spray: can we improve the taste? A randomised, double-blind, crossover study.

OBJECTIVE: Co-Phenylcaine Forte is a nasal spray routinely prescribed by otolaryngologists in Australia. The taste of Co-Phenylcaine Forte is typically described as unpleasant. This study sought to improve the overall patient experience associated with Co-Phenylcaine Forte by generating a Co-Phenylcaine Forte formulation, referred to as Co-Phenylcaine Zest, which contains an added vanilla flavour and masking agent. METHODS: Participants were randomised to receive two actuations of Co-Phenylcaine Forte in each nostril followed by two actuations of Co-Phenylcaine Zest, or vice versa. There was a 6-36-hour washout period between each treatment. After the administration of each spray, participants completed a questionnaire to rate various sensory attributes of each formulation on seven-point ordinal scales. Patients reported their overall formulation preference after receiving both treatments. RESULTS: A total of 86 participants completed the trial. Seventy-four per cent of patients preferred Co-Phenylcaine Zest, 21 per cent preferred Co-Phenylcaine Forte and 5 per cent had no preference (p < 0.001). The satisfaction score associated with Co-Phenylcaine Zest was 1.22 points greater than with Co-Phenylcaine Forte (p < 0.001). CONCLUSION: A novel formulation of Co-Phenylcaine Forte was created by adding a flavour and a masking agent; this formulation was preferred by most patients.

Prevalence, incidence, and risk factors for shoulder and neck dysfunction after neck dissection: A systematic review.

INTRODUCTION: Shoulder pain and dysfunction may occur following neck dissection among people being treated for head and neck cancer. This systematic review aims to examine the prevalence and incidence of shoulder and neck dysfunction after neck dissection and identify risk factors for these post-operative complications. METHODS: Electronic databases (Pubmed, CINAHL, EMBASE, Cochrane) were searched for articles including adults undergoing neck dissection for head and neck cancer. Studies that reported prevalence, incidence or risk factors for an outcome of the shoulder or neck were eligible and assessed using the Critical Review Form - Quantitative Studies. RESULTS: Seventy-five articles were included in the final review. Prevalence rates for shoulder pain were slightly higher after RND (range, 10-100%) compared with MRND (range, 0-100%) and SND (range, 9-25%). The incidence of reduced shoulder active range of motion depended on surgery type (range, 5-20%). The prevalence of reduced neck active range of motion after neck dissection was 1-13%. Type of neck dissection was a risk factor for shoulder pain, reduced function and health-related quality of life. CONCLUSIONS: The prevalence and incidence of shoulder and neck dysfunction after neck dissection varies by type of surgery performed and measure of dysfunction used. Pre-operative education for patients undergoing neck dissection should acknowledge the potential for post-operative shoulder and neck problems to occur and inform patients that accessory nerve preservation lowers, but does not eliminate, the risk of developing musculoskeletal complications.

Olfactory neuroblastoma: 14-year experience at an Australian tertiary centre and the role for longer-term surveillance.

BACKGROUND: Olfactory neuroblastoma is a rare sinonasal malignancy, with poorly defined treatment protocols. Management at a tertiary centre was retrospectively evaluated to inform future treatment and follow up. METHODS: Cases treated with curative intent (2000-2014) were included. Data were collected, and overall and disease-free survival rates were calculated. RESULTS: Eleven cases were identified, with a median follow up of 87 months. One patient was Kadish stage A, one was stage B, eight were stage C and one was stage D. The latter patient underwent chemoradiotherapy alone. The remaining patients proceeded to: endoscopic-assisted wide local excision (n = 2), anterior craniofacial resection (n = 4) or endoscopic craniofacial resection (n = 4). No patients had primary nodal disease or elective neck treatment. One patient had neoadjuvant chemoradiation. Six patients had post-operative radiotherapy; three received adjuvant chemotherapy. Two patients had late cervical node failure, and proceeded to neck dissection and post-operative radiotherapy. Two patients had late local recurrence. Ten-year overall and disease-free survival rates were 68.2 and 46.7 per cent, respectively. CONCLUSION: Longer-term follow up is supported given the incidence of late regional and local recurrence. Prophylactic treatment of cervical nodes in locally advanced disease is an area for further investigation.

Role of targeted magnetic resonance imaging sequences in the surgical management of anterior skull base pathology.

BACKGROUND: The skull base is a highly complex anatomical region that provides passage for important nerves and vessels as they course into and out of the cranial cavity. Key to the management of pathology in this region is a thorough understanding of the anatomy, with its variations, and the relationship of various neurovascular structures to the pathology in question. Targeted high-resolution magnetic resonance imaging on high field strength magnets can enable the skull base surgeon to understand this intricate relationship and deal with the pathology from a position of relative advantage. OBJECTIVE: With the help of case studies, this paper illustrates the application of specialised magnetic resonance techniques to study pathology of the orbital apex in particular. CONCLUSION: The fine anatomical detail provided gives surgeons the ability to design an endonasal endoscopic procedure appropriate to the anatomy of the pathology.

Cellular and molecular mechanisms of chronic rhinosinusitis and potential therapeutic strategies: review on cytokines, nuclear factor kappa B and transforming growth factor beta.

BACKGROUND: Chronic rhinosinusitis is characterised by persistent inflammation of the sinonasal mucosa. Multiple pathophysiological mechanisms are likely to exist. Previous research has focused predominantly on T-helper type cytokines to highlight the inflammatory mechanisms. However, proteins such as nuclear factor kappa B and transforming growth factor beta are increasingly recognised to have important roles in sinonasal inflammation and tissue remodelling. OBJECTIVE: This review article explores the roles of T-helper type cytokines, nuclear factor kappa B and transforming growth factor beta in the pathophysiological mechanisms of chronic rhinosinusitis. An understanding of these mechanisms will allow for better identification and classification of chronic rhinosinusitis endotypes, and, ultimately, improved therapeutic strategies.

Sinonasal outcomes following endoscopic anterior skull base surgery with nasoseptal flap reconstruction: a prospective study.

OBJECTIVE: To assess nasal morbidity resulting from nasoseptal flap use in the repair of skull base defects in endoscopic anterior skull base surgery. METHODS: Thirty-six patients awaiting endoscopic anterior skull base surgery were prospectively recruited. A nasoseptal flap was used for reconstruction in all cases. Patients were assessed pre-operatively and 90 days post-operatively via the Sino-Nasal Outcome Test 20 questionnaire and visual analogue scales for nasal obstruction, pain, secretions and smell; endoscopic examination findings and mucociliary clearance times were also recorded. RESULTS: Sino-Nasal Outcome Test 20 questionnaire data and visual analogue scale scores for pain, smell and secretions showed no significant differences between pre- and post-operative outcomes, with visual analogue scale scores for nasal obstruction actually showing a significant improvement (p = 0.0007). A significant deterioration for both flap and non-flap sides was demonstrated post-operatively on endoscopic examination (p = 0.002 and p = 0.02 respectively). CONCLUSION: Whilst elevation of a nasoseptal flap in endoscopic surgery of the anterior skull base engendered significant clinical deterioration on examination post-operatively, quality of life outcomes showed that no such deterioration was subjectively experienced by the patient. In fact, there was significant nasal airway improvement following nasoseptal flap reconstruction.

T-category remains an important prognostic factor for oropharyngeal carcinoma in the era of human papillomavirus.

AIMS: To determine prognostic factors for locoregional relapse (LRR), distant relapse and all-cause death in a contemporary cohort of locoregionally advanced oropharyngeal squamous cell carcinoma (OSCC) treated with definitive chemoradiotherapy or radiotherapy alone. MATERIALS AND METHODS: OSCC patients treated with definitive radiotherapy between 2005 and 2010 were identified from a prospective head and neck database. Patient age, gender, smoking history, human papillomavirus (HPV) status, T- and N-category, lowest involved nodal level and gross tumour volume of the primary (GTV-p) and nodal (GTV-n) disease were analysed in relation to LRR, distant relapse and death by way of univariate and multivariate analysis. RESULTS: In total, 130 patients were identified, 88 HPV positive, with a median follow-up of 42 months. On multivariate analysis HPV status was a significant predictor of LRR (hazard ratio 0.15; 95% confidence interval 0.05-0.51) and death (hazard ratio 0.29; 95% confidence interval 0.14-0.59) but not distant relapse (hazard ratio 0.53, 95% confidence interval 0.22-1.27). Increasing T-category was associated with a higher risk of LRR (hazard ratio 1.80 for T3/4 versus T1/2; 95% confidence interval 1.08-2.99), death (hazard ratio 1.37, 95% confidence interval 1.06-1.77) and distant relapse (hazard ratio 1.35; 95% confidence interval 1.00-1.83). Increasing GTV-p was associated with increased risk of distant relapse and death. N3 disease and low neck nodes were significant for LRR, distant relapse and death on univariate analysis only. CONCLUSION: Tumour HPV status was the strongest predictor of LRR and death. T-category is more predictive of distant relapse and may provide additional prognostic value for LRR and death when accounting for HPV status.

Causes and consequences of anterior pharyngeal pouch after total laryngectomy.

OBJECTIVES: To assess the frequency of anterior pharyngeal pouch formation after total laryngectomy, and to discuss the causes and consequences of anterior pharyngeal pouch formation. STUDY DESIGN: A prospective, observational study of 43 patients undergoing total laryngectomy. METHODS: Data collected included laryngeal defect closure type, tumour staging and demographic information. A barium swallow was performed on day 7-14 after surgery to assess for anterior pharyngeal pouch formation and fistula formation. RESULTS: The incidence of anterior pharyngeal pouch formation was 47 per cent. Patients who did not have an anterior pharyngeal pouch on swallow imaging assessment were less likely to develop a pharyngo-cutaneous fistula. There was no statistically significant association between laryngeal defect closure type and anterior pharyngeal pouch formation. CONCLUSION: The anterior pharyngeal pouch is a dynamic phenomenon best investigated with a fluoroscopic swallow imaging study. Its causes are multi-factorial. Absence of an anterior pharyngeal pouch appears to confer protection against pharyngo-cutaneous fistula formation, hastening commencement of adjuvant therapy and an oral diet.

Detecting and defining the anatomic extent of large nerve perineural spread of malignancy: comparing "targeted" MRI with the histologic findings following surgery.

BACKGROUND: The accurate preoperative identification of the extent of perineural spread (PNS) of malignancy along a cranial nerve is vital to the design of an appropriate surgical resection. Our purpose was to determine the sensitivity of targeted MRI in predicting the presence of disease and the anatomic extent of spread when compared with histologic findings. METHODS: A retrospective review was performed of 25 patients with PNS who had targeted MRI and surgery to excise perineural tumor (2002-2008). RESULTS: MRI detected PNS in 30 of 30 nerves (100%) with 1 false positive. MRI correctly identified the extent of spread based on histology in 25 of 30 nerves (83.3%). In 4 of 30 cases (13.3%) MRI underestimated the extent of spread proximal to the Gasserian ganglion that, if diagnosed preoperatively, may have deemed the patient inoperable. CONCLUSIONS: MRI demonstrated the presence and anatomic extent of PNS in the majority of cases. MRI may underestimate microscopic spread proximal to the Gasserian ganglion.

Myxoma of the masticator space.

We describe a rare case of a surgically proven myxoma arising within the masticator space probably from a pterygoid muscle. The lesion showed characteristic hyperintensity on T2-weighted images and did not enhance following gadolinium.

Radiation-induced myelopathy in long-term surviving metastatic spinal cord compression patients after hypofractionated radiotherapy: a clinical and magnetic resonance imaging analysis.

BACKGROUND AND PURPOSE: Hypofractionated radiotherapy is often administered in metastatic spinal cord compression (MSCC), but no studies have been published on the incidence of radiation-induced myelopathy (RIM) in long-term surviving patients. Our report addresses this topic. PATIENTS AND METHODS: Of 465 consecutive MSCC patients submitted to radiotherapy between 1988 and 1997, 13 live patients (seven females, six males, median age 69 years, median follow-up 69 months) surviving for 2 years or more were retrospectively reviewed to evaluate RIM. All patients underwent radiotherapy. Eight patients underwent a short-course regimen of 8 Gy, with 7 days rest, and then another 8 Gy. Five patients underwent a split-course regimen of 5 Gy x 3, 4 days rest, and then 3 Gy x 5. Only one patient also underwent laminectomy. Full neurological examination and magnetic resonance imaging (MRI) were performed. RESULTS: Of 12 patients submitted to radiotherapy alone, 11 were ambulant (eight without support and three with support) with good bladder function. In nine of these 11 patients, MRI was negative; in one case MRI evidenced an in-field relapse 30 months after the end of radiotherapy, and in the other, two new MSCC foci outside the irradiated spine. In the remaining patient RIM was suspected at 18 months after radiotherapy when the patient became paraplegic and cystoplegic, and magnetic resonance images evidenced an ischemic injury in the irradiated area. The only patient treated with surgery plus postoperative radiotherapy worsened and remained paraparetic. Magnetic resonance images showed cord atrophy at the surgical level, explained as an ischemic necrosis due to surgery injury. CONCLUSIONS: On the grounds of our data regarding RIM in long-term surviving MSCC patients, we believe that a hypofractionated radiotherapy regimen can be used for the majority of patients. For a minority of patients, more protracted radiation regimens could be considered.

Regional node failure in patients with four or more positive lymph nodes submitted to conservative surgery followed by radiotherapy to the breast.

A retrospective analysis was conducted to evaluate the incidence of nodal failure in a subgroup of patients who had T1-T2 breast cancer and four or more positive nodes. Sixty-four 5 patients ranging in age from 29 to 73 years (median, 51) received conservative surgery followed by radiotherapy to the breast between November 1980 and May 1995. Adjuvant chemotherapy was administered to 56 patients, 27 of whom were also treated with tamoxifen, which was used alone in 5 patients. Three patients received no adjuvant treatment. Sixty-two patients are evaluable for regional node failure. There were 10 nodal failures, 4 in the axillary and 6 in the supraclavicular regions, in 9 patients, at a median of 56.5 and 27 months, respectively. There was no internal mammary node failure. Median follow-up was 72.6 months. The 10-year probability of developing axillary and supraclavicular failure is 13.9 +/- 7.7% and 10.5 +/- 4.1%, respectively. Prognosis was better for patients with axillary and breast recurrence and worse when relapse was in the supraclavicular region. On the basis of our results and data already published in premenopausal patients, we believe that radiotherapy to the supraclavicular region should be considered in patients with four or more positive axillary nodes, after a complete dissection.

Anterior approaches in juvenile nasopharyngeal angiofibromas with intracranial extension.

Although surgery is regarded as the mainstay of treatment for juvenile nasopharyngeal angiofibromas (JNAs), ancillary treatment modalities such as radiotherapy and on rare occasions chemotherapy are still recommended by many for intracranial extension with apparent radiologic involvement of the cavernous sinus and internal carotid artery. Further, most authors undertaking surgical excision of this subgroup of patients would recommend a lateral or combined frontal and lateral approach for its removal. In a series of 49 cases of JNA, 14 were found during surgery to have intracranial extradural extension; the anterior approach was used for their removal. Although in these cases, on radiography the cavernous sinus often looked to be invaded and the internal carotid artery was displaced superolaterally, there was no difficulty in establishing a plane of dissection. Total removal was achieved in 11 of the 14 cases with a single-stage procedure. Of the 3 cases with residual tumor, only 1 occurred intracranially. Removal was achieved by a subtemporal approach in this case. For the extracranial residual tumors 1 required a midface degloving and the other, with a 1-cm residual tumor in the nasopharynx, has been treated conservatively for 6 years with no evidence of growth. No deaths or significant complications have occurred, and radiotherapy has not been required. We conclude that JNAs are tumors with a predilection for spread but that rarely invade dura, acting instead to displace it. We believe that surgery is the method of choice for treating these lesions and that an anterior surgical approach with microsurgical techniques should be used in the first instance. In the last 2 cases we preferred a midface degloving technique to avoid facial scarring and because this approach allows a widening of the surgical field if needed by the performance of bilateral maxillary free bone flaps. On the rare occasion that a lateral approach, with its attendant permanent conductive hearing loss, is found to be necessary for total tumor removal, this can be done as a staged procedure. This may be necessary when the tumor has spread lateral to the horizontal internal carotid artery.

[Postoperative pain control in the Trento community hospital. Perception of pain by the nurses]. / Il controllo del dolore nel postoperatorio nell'ospedale civile di Trento: la percezione da parte degli infermieri.

The College of Nurses of Trento (Collegio IPASVI) promoted a call for research works done by nurses, to award a prize to those judged worthy. The three best works were respectively on concordance on triage classification between doctors and nurses; on the results of organizational and educational interventions on the reduction of needle-stick injuries; and on the differences on postoperative pain assessment between nurses and patients. The final reports were later discussed as part of a training exercise aiming at improving the skill of scientific writing and they are published here, together with some comments that emphasize areas of improvement in data analysis and interpretation and some broader issues related to nursing research.

Allogeneic matched T-cell-depleted bone marrow transplantation for acute leukemia patients.

PURPOSE: We evaluated the efficacy and toxicity of a conditioning regimen designed to overcome the increased risk of rejection and relapse associated with T-cell-depleted bone marrow transplants. PATIENTS AND METHODS: Fifty-four patients with acute leukemia received an allogeneic T-depleted bone marrow transplant from an HLA-matched (n=52) or one locus mismatched (n=2) sibling donor between June 1989 and November 1993. Nineteen acute myeloid leukemia patients and 17 acute lymphoid leukemia patients were in complete remission, and 11 acute myeloid leukemia patients and 7 acute lymphoid leukemia patients were in relapse. Patients were preconditioned with hyperfractionated total body irradiation of 1.2 Gy three times a day on days -9 to -6 (total 14.4 Gy), 10 mg/kg thiotepa on day -5, 4 mg/kg rabbit antithymocyte globulin on days -4 to -1, and 50 mg/kg cyclophosphamide on days -3 and -2. RESULTS: All patients were fully engrafted at a median of 15 days after transplant. No patient rejected the transplant or developed acute or chronic graft-versus-host disease. Of 19 patients with acute myeloid leukemia in complete remission, 14 survive. Four of the 11 patients with acute myeloid leukemia in relapse survive. Twelve acute myeloid leukemia patients died (three of relapse, eight of toxicity, one of other causes). Eleven of 24 patients with acute lymphoid leukemia (one treated in relapse) are alive in complete remission; the other 13 died (nine of relapse, four of toxicity). Interstitial pneumonia, the main cause of toxic death, occurred in 9.26% of total patients. The median follow-up time at this writing is 30 months. CONCLUSIONS: The absence of rejection and graft-versus-host disease and the relatively low relapse and toxicity rates are evidence for the efficacy of our conditioning regimen.