Using comprehensive genomic and functional analyses for resolving genotype-phenotype mismatches in children with suspected CMMRD in Lebanon: an IRRDC study.

Constitutional mismatch repair deficiency (CMMRD) is an aggressive and highly penetrant cancer predisposition syndrome. Because of its variable clinical presentation and phenotypical overlap with neurofibromatosis, timely diagnosis remains challenging, especially in countries with limited resources. Since current tests are either difficult to implement or interpret or both we used a novel and relatively inexpensive functional genomic assay (LOGIC) which has been recently reported to have high sensitivity and specificity in diagnosing CMMRD. Here we report the clinical and molecular characteristics of nine patients diagnosed with cancer and suspected to have CMMRD and highlight the challenges with variant interpretation and immunohistochemical analysis that led to an uncertain interpretation of genetic findings in 6 of the 9 patients. Using LOGIC, we were able to confirm the diagnosis of CMMRD in 7 and likely exclude it in 2 patients, resolving ambiguous result interpretation. LOGIC also enabled predictive testing of asymptomatic siblings for early diagnosis and implementation of surveillance. This study highlights the varied manifestations and practical limitations of current diagnostic criteria for CMMRD, and the importance of international collaboration for implementing robust and low-cost functional assays for resolving diagnostic challenges.

Pediatric oncology infrastructure and workforce training needs: a report from the Pediatric Oncology East and Mediterranean (POEM) Group.

BACKGROUND: Inadequate numbers of trained healthcare providers (HCPs), contribute to poor pediatric oncology (PO) outcomes, particularly in low- and lower middle-income countries (L/LMICs). An understanding of the characteristics of the workforce challenges are vital for addressing these problems. METHODS: The Pediatric Oncology East and Mediterranean (POEM) Group surveyed PO centers in countries of the North Africa, Middle East, Central Asia and Indian subcontinent on infrastructure and workforce capacity, service availability, and training opportunities for HCPs. Participating centers were categorized by the World Bank income levels for their countries and correlated with services, workload and staffing characteristics, and training needs. RESULTS: Fifty of 82 member-centers (61%) from 21 countries responded to the survey. 299 pediatric oncologists and 1,176 nurses treated 12,496 new PO patients/year, with a 1,451 beds utilization. The majority (71%) of new cases occurred in L/LMICs. The availability of HCPs correlated with country income level, as did pediatric subspecialty access, while availability of support services was unrelated. Twenty-five centers in 11 countries offered PO fellowship training for physicians, whereas 13 PO nurse training centers in 9 countries had the capacity to train 273 nurses annually. The survey respondents indicated that, among their existing workforce, an average of 3·5 physicians and 14 nurses per institution would benefit from additional PO training opportunities. CONCLUSIONS: The participating centers exhibited intra-regional heterogeneity in financial resources, infrastructure, workload, workforce, and medical services. Our findings provide insight into the disparities and regional resources available to POEM, which can be mobilized to rectify specific deficiencies. This article is protected by copyright. All rights reserved.

Hyper-CVAD combined with Venetoclax for relapsed pediatric blastic plasmacytoid dendritic cell neoplasm (BPDCN): A case report and literature review.

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a very rare type of leukemia in children, Although BPDCN is a chemo-sensitive tumor, the relapse rate is very high. Tagraxofusp, which is a CD123-directed cytotoxin has been used as a targeted therapy and has shown promising results in patients with either untreated or relapsed BPDCN. There is also a good response with Venetoclax, a selective BCL2 inhibitor, as a single agent or in combination with chemotherapy. Here, we described a case of a pediatric patient with BPDCN who was treated initially with ALL-based regimen followed by Allogeneic hematopoietic stem-cell transplantation (HSCT) and salvaged with Hyper-CVAD combined with Venetoclax after testicular relapse 11 months post Allogeneic HSCT.

Diagnosis and Treatment of a Patient With Severe Combined Immunodeficiency Due to a Novel Homozygous Mutation in the IL-7Rα Chain.

The interleukin-7 receptor (IL-7R) is expressed on lymphoid cells and plays an important role in the development, homeostasis, survival, and proliferation of T cells. Bi-allelic mutations in the IL-7Rα chain abolish T cell development and function resulting in severe combined immunodeficiency disease. In this manuscript, we investigate a 1 year-old patient born to consanguineous parents, who suffered from autoimmune hemolytic anemia since birth associated with recurrent severe infections. Flow cytometric analysis of the patient's peripheral blood demonstrated elevated numbers of B and NK cells, decreased numbers of T cells, defective thymic output, a predominance of memory T cells, and absent T cell proliferation. Next Generation Sequencing identified a novel homozygous pathogenic mutation in IL7RA (c.379G>A) that resulted in aberrant IL7RA RNA splicing and absent IL-7Rα expression. The patient was successfully transplanted using her HLA-matched relative as donor. One year after transplant, the patient is clinically stable with normal reconstitution of donor T cells that express IL-7Rα, a significant increase in the percentages of recent thymic emigrant and peripheral T cells, normalization of naïve and memory T cells, and restoration of her T cell's proliferative response. Therefore, using genetic and functional approaches, we identified a novel deleterious mutation in IL-7Rα that results in T-B+NK+ phenotype, and report successful hematopoietic stem cell transplantation of the patient. This represents the first bedside-to-bench-and-back case entirely performed on a patient with severe combined immunodeficiency at the American University of Beirut Medical Center.

Vincristine-induced neurotoxicity in pediatric patients with rhabdomyosarcoma: A retrospective analysis of clinical features and outcome.

Vincristine is an essential component of rhabdomyosarcoma treatment. However, it can cause motor neurotoxicity, necessitating dose reductions. We retrospectively reviewed the rates and patterns of vincristine-induced motor neuropathy in children treated for rhabdomyosarcoma, and investigated effects on outcome. Fifteen of 43 patients (35%) developed motor neuropathies necessitating dose reductions, which ranged from 1.7% to 58% of planned cumulative dose. Older age was the only significant clinical risk factor. Almost half (47%) recovered during treatment with subsequent dose escalation. Most patients had complete resolution of symptoms upon follow-up. There was no discernible effect of treatment reduction on survival or relapse rates.

Pediatric oncology infrastructure and workforce training needs: A report from the Pediatric Oncology East and Mediterranean (POEM) Group.

BACKGROUND: Inadequate numbers of trained health care providers (HCPs) contribute to poor pediatric oncology (PO) outcomes, particularly in low- and lower middle-income countries (L/LMICs). An understanding of the characteristics of the workforce challenges is vital for addressing these problems. METHODS: The Pediatric Oncology East and Mediterranean (POEM) Group surveyed PO centers in countries of North Africa, Middle East, Central Asia, and Indian subcontinent on infrastructure and workforce capacity, service availability, and training opportunities for HCPs. Participating centers were categorized by the World Bank income levels for their countries and correlated with services, workload and staffing characteristics, and training needs. RESULTS: Fifty of 82 member centers (61%) from 21 countries responded to the survey. Two hundred ninety-nine pediatric oncologists and 1176 nurses treated 12 496 new PO patients/year, with a 1451-bed utilization. The majority (71%) of new cases occurred in L/LMICs. The availability of HCPs correlated with country income level, as did pediatric subspecialty access, while availability of support services was unrelated. Twenty-five centers in 11 countries offered PO fellowship training for physicians, whereas 13 PO nurse training centers in nine countries had the capacity to train 273 nurses annually. The survey respondents indicated that, among their existing workforce, an average of 3.5 physicians and 14 nurses per institution would benefit from additional PO training opportunities. CONCLUSIONS: The participating centers exhibited intraregional heterogeneity in financial resources, infrastructure, workload, workforce, and medical services. Our findings provide insight into the disparities and regional resources available to POEM, which can be mobilized to rectify specific deficiencies.

Treatment-induced cerebral sinus venous thrombosis in childhood acute lymphoblastic malignancies: New risk factors to consider.

BACKGROUND: Cerebral sinus venous thrombosis (CSVT) is one of the many side effects encountered during acute lymphoblastic leukemia (ALL) therapy. Due to the rarity of cases, lack of data, and consensus management, no recommendations exist to target the population at risk. METHODS: This is a retrospective chart review of 229 consecutive patients diagnosed with ALL with an age range of 1-21 years, treated at the Children's Cancer Center of Lebanon between October 2007 and February 2018. RESULTS: The incidence of CSVT was 10.5%. Using univariate analysis, increased risk of CSVT was observed with male gender, age >10 years, T-cell immunophenotype, intermediate/high-risk disease, maximum triglyceride (TG) level of >615 mg/dl, presence of mediastinal mass, and larger body surface area (BSA). With multivariate analysis, the only statistically significant risk factors were maximum TG level, BSA, presence of mediastinal mass, and risk stratification (intermediate/high risk). CONCLUSION: Our study was able to unveil TG level of >615 mg/dl, mediastinal mass, and a larger BSA as novel risk factors that have not been previously discussed in the literature.

Primary Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Kidney: The MD Anderson Cancer Center Experience.

Limited information exists on the clinical behavior of the Ewing sarcoma family of tumors (ESFT) of the kidney. We reviewed the records of 30 patients (aged 8-69 years) with ESFT of the kidney seen at our institution between 1990 and 2013. We analyzed the event-free survival (EFS) and overall survival (OS) for associations with patient demographics, disease group, tumor size, tumor thrombus, and treatment. Six patients (20%) had tumors confined to the kidney (Group I), seven (23.3%) had local tumor extension beyond the kidney (Group II), and 17 (56.7%) had distant metastasis at diagnosis (Group III). Twenty-five (83.3%) patients underwent radical (19 upfront, five delayed) or partial (one upfront) nephrectomy, 25 (83.3%) chemotherapy and four (13.3%) radiotherapy. The 4-year EFS and OS were 43% (95% CI, 26-61%) and 63% (95% CI, 46-81%), respectively. EFS and OS were significantly associated with disease group and chemotherapy (p < 0.039). The presence of tumor thrombus in renal vein and/or inferior vena cava was associated with worse EFS (p = 0.053). Patients with disease confined to the kidney treated with nephrectomy and adjuvant chemotherapy have favorable outcomes. Local tumor extension beyond the kidney, tumor thrombus, and distant metastasis are unfavorable factors that warrant intensification or novel approaches of therapy.

Isolated Central Nervous System Relapse Following Treatment Reduction in Low-risk Acute Lymphoblastic Leukemia at the Children's Cancer Center of Lebanon.

The aim of this trial was to decrease the incidence of life-threatening infections by decreasing the dose and the duration of dexamethasone treatment during maintenance therapy. This was a prospective, nonrandomized trial of low-risk acute lymphoblastic leukemia patients 1 to 18 years of age who were treated at the Children's Cancer Center of Lebanon (CCCL). Patients consecutively diagnosed between 2002 and 2013 were divided into groups 1 and 2 receiving total dexamethasone doses of 1144 and 618 mg/m, respectively. A total of 84 patients were assigned to group 1 and 33 patients to group 2. The 5-year cumulative incidence of isolated central nervous system relapse increased from (n=0% [95% confidence interval: 0%-4.4%]) in group 1 to 9.1% [95% confidence interval: 3%-23%]; P=0.021) in group 2. Decreasing cumulative dose of dexamethasone for low-risk childhood acute lymphoblastic leukemia patients aiming to avoid serious viral infections led to a significant increase in isolated central nervous system relapse.

Establishment of a formal program for retinoblastoma: Feasibility of clinical coordination across borders and impact on outcome.

Retinoblastoma is an ocular tumor that occurs in young children, in either heritable or sporadic manner. The relative rarity of retinoblastoma, and the need for expensive equipment, anesthesia, and pediatric ophthalmologic expertise, are barriers for effective treatment in developing countries. Also, with an average age-adjusted incidence of two to five cases per million children, patient number limits development of local expertise in countries with small populations. Lebanon is a small country with a population of approximately 4.5 million. In 2012, a comprehensive retinoblastoma program was formalized at the Children's Cancer Institute (CCI) at the American University of Beirut Medical Center, and resources were allocated for efficient interdisciplinary coordination to attract patients from neighboring countries such as Syria and Iraq, where such specialized therapy is also lacking. Through this program, care was coordinated across hospitals and borders such that patients would receive scheduled chemotherapy at their institution, and monthly retinal examinations and focal laser therapy at the CCI in Lebanon. Our results show the feasibility of successful collaboration across borders, with excellent patient and physician adherence to treatment plans. This was accompanied by an increase in patient referrals, which enables continued expertise development. However, the majority of patients presented with advanced intraocular disease, necessitating enucleation in 90% of eyes in unilateral cases, and more than 50% of eyes in bilateral cases. Future efforts need to focus on expanding the program that reaches to additional hospitals in both countries, and promoting early diagnosis, for further improvement of globe salvage rates.

Correlation Between MYCN Gene Status and MYCN Protein Expression in Neuroblastoma: A Pilot Study To Propose the Use of MYCN Immunohistochemistry in Limited-Resource Areas.

PURPOSE: The most significant adverse risk factor for neuroblastoma (NB) is MYCN gene amplification, which strongly associates with high-risk disease. Fluorescent in situ hybridization (FISH) is considered the best method to evaluate MYCN gene status. However, it requires a laboratory that can perform highly complex testing, specialized personnel, and costly reagents. Herein, we aimed to investigate the feasibility of using immunohistochemistry (IHC) to detect MYCN protein expression in lieu of FISH, a strategy potentially useful in areas with limited resources. METHODS: A pilot cohort of 78 patients with NB, including 34 of Middle Eastern descent (MED) who had a higher prevalence of MYCN gene amplification (44.11%) and 44 of North American descent (NAD), nine (20.45%) of whom had MYCN amplification, was evaluated with IHC for MYCN protein. Correlations of FISH results and protein expression are presented. RESULTS: A positive correlation between MYCN gene amplification and protein expression by IHC was seen in 22 (91.66%) of the 24 MYCN-amplified NB cases-14 (93.33%) of 15 patients of MED and eight (88.88%) of nine patients of NAD. Agreement between negative FISH and negative IHC results was noted in 18 (94.73%) patients of MED and 34 (97.14%) patients of NAD. Two cases had weak protein expression but no gene amplification (MED: n = 1; 5.0%; NAD: n = 1; 2.9%). CONCLUSION: An excellent overall correlation between MYCN gene status by FISH and MYCN protein expression by IHC was confirmed. MYCN IHC in NB with reflexing to FISH in equivocal cases is potentially useful in a limited-resource setting. Evaluation of effectiveness using a larger cohort and optimization to perform MYCN IHC manually is needed.

Genetic polymorphisms in candidate genes are not associated with increased vincristine-related peripheral neuropathy in Arab children treated for acute childhood leukemia: a single institution study.

OBJECTIVE: The aim of this study was to evaluate the potential association between candidate genetic polymorphisms and vincristine-related peripheral neuropathy in Arab children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: This is a retrospective evaluation of 133 Arab children treated for ALL at the Children's Cancer Center of Lebanon. Incidence and severity of, as well as the timing (in weeks) at which grade 2 or higher peripheral neuropathy occurred were recorded. Genotyping for ABCB1 (rs1045642), ABCB1 (rs1128503), ABCC2 (rs717620), CEP72 (rs924607), ETAA1 (rs17032980), and MTNR1B (rs12786200) was performed. RESULTS: A total of 26 (19.5%) individuals developed peripheral neuropathy, three of which occurred during the induction phase. No statistically significant associations were revealed for any of the polymorphisms with either incidence of vincristine-related toxicity, toxicity severity, or time to the first episode of grade 2 or higher vincristine-related peripheral neuropathy. CONCLUSION: This study presents the first pharmacogenetic analysis of vincristine-related peripheral neuropathy in children with ALL in an Arab country. We have shown that genetic polymorphisms in candidate genes are not associated with peripheral neuropathy secondary to chronic therapy with high-dose vincristine (2 mg/m) during the continuation phase. Concerning CEP72, our results are in line with the findings from the St Jude cohort of children treated for ALL with higher vincristine doses during chronic treatment. Larger high-throughput genetic analyses may be warranted to evaluate variants in other candidate genes such as CYP3A5 and reveal new nonpreviously reported alleles that may be peculiar to this region of the world.

Displaced children with cancer in Lebanon: A sustained response to an unprecedented crisis.

BACKGROUND: The unrest in Syria has resulted in an escalating refugee crisis. The postwar lack of health care infrastructure in Iraq has also resulted in Iraqis seeking health care in neighboring countries. Pediatric cancer is largely curable, although its treatment is expensive and complex. Strategies to implement pediatric cancer care with curative intent in these vulnerable populations are lacking. METHODS: To assess the feasibility of a collaborative approach for the provision of care to displaced children with cancer, this study reviewed the experience of the authors over the past 6 years in Lebanon, the country with the highest number of refugees per capita in the world. RESULTS: The American University of Beirut Medical Center and the Children's Cancer Center of Lebanon Foundation, in partnership with St. Jude Children's Research Hospital and the American Lebanese Syrian Associated Charities, established 3 successive funding programs to treat displaced children with cancer along with a continuous assessment of resource utilization. Between 2011 and 2017, 575 non-Lebanese children suspected to have cancer were evaluated. Of those, 311 received direct medical support, with 107 receiving full-treatment coverage and 204 receiving limited-workup/specialty services; the remaining 264 patients received medical consultations. CONCLUSIONS: In addition to providing lifesaving humanitarian support, the coordination of care delivery, including the establishment of guidelines for prioritization, can help direct future efforts. Many patients continue to be in dire need of support, and this should be addressed via collaboration among governmental, nongovernmental, and health care organizations. Cancer 2018;124:1464-72. © 2018 American Cancer Society.

Recurrent desmoplastic small round cell tumor responding to an mTOR inhibitor containing regimen.

Desmoplastic small round cell tumor (DSRCT) is a rare mesenchymal tumor that typically presents with multiple abdominal masses. Initial treatment is multimodal in nature. Patients with relapsed DSRCT have a poor prognosis, and there are no standard therapies. We report our experience with five patients treated with vinorelbine, cyclophosphamide, and temsirolimus (VCT). Median number of VCT courses delivered was 7 (range 4-14 courses), and partial response was observed in all patients. Median time to progression or relapse was 8.5 months (range 7-16 months). Neutropenia and mucositis were most common toxicities (n = 4 each).

Routine surveillance imaging after end of therapy for pediatric extracranial tumors: A retrospective analysis.

Frequent surveillance imaging is routine practice for pediatric patients after cancer therapy. This retrospective study evaluated the follow-up of 301 children with extracranial tumors diagnosed between 2002 and 2012, at a tertiary pediatric cancer center in Beirut, Lebanon. Recurrence occurred in 15% of patients, at a median of 12 months after end of primary therapy. Outcome was not different comparing patients with recurrence detected via imaging surveillance versus clinically. False positive findings in 55 patients led to further interventions. These results raise important questions regarding benefit of current surveillance practices as standard care, especially in countries with limited resources.

Pediatric cancer pathology review from a single institution: Neuropathology expert opinion is essential for accurate diagnosis of pediatric brain tumors.

BACKGROUND AND OBJECTIVES: Second pathology review has been reported to improve accuracy in oncologic diagnoses, including pediatric malignancies. We assessed the impact of second review on the diagnosis of pediatric malignancies at a tertiary care referral center in Beirut, Lebanon. METHODS: Pathology reports of patients treated at the Children's Cancer Institute in Lebanon were retrospectively reviewed for the period 2008-2016 and compared with same samples' diagnoses at St. Jude Children's Research Hospital. Diagnostic disagreements were divided into major, minor, and none based on their effect on diagnosis and/or patient management. RESULTS: Second review was requested for 171 cases, accounting for 19% of all cases during that period. Second opinion was mostly requested for brain tumors (62% of all brain tumor cases) and neuroblastoma for NMYC testing (65% of all neuroblastoma), while hematologic malignancies had the fewest referrals (3% of all hematologic cases). Major disagreements in second review occurred in 20 cases (12% of total), and minor disagreements in 21 cases (12% of total). The largest proportion of major disagreements (71%) occurred in pediatric brain tumors, and novel molecular tests contributed to the diagnosis in 55% of these cases. CONCLUSIONS: The availability of a specialized pediatric neuropathologist and a basic panel of relevant molecular testing are essential for appropriate diagnosis of pediatric brain tumors. Centers that do not have the available infrastructure in place can benefit greatly from second review referrals for this challenging subset of tumors.

Etiologies and Impact of Readmission Rates in the First 180 Days After Hematopoietic Stem Cell Transplantation in Children, Adolescents, and Young Adults.

INTRODUCTION: High rates of patients require readmission to the hospital within 6 months of hematopoietic stem cell transplantation (HSCT). We investigated the relationship between readmission rates and outcomes after HSCT in children, adolescents, and young adults (CAYA). MATERIALS AND METHODS: A retrospective analysis of patients (26 years or younger) treated with HSCT was conducted. RESULTS: A chart review of 435 CAYA who underwent HSCT from 2008 to 2015 revealed that 171 patients (39%) had at least 1 hospital readmission within 180 days of transplant; 87% received allogeneic and 13% received autologous HSCT. A total of 312 readmission events were reported. The median follow-up time was 31 months. Documented infection (n=99) and graft-versus-host disease complications (n=60) were the most common causes. Higher than 2 readmission rates were associated with lower overall survival (OS) (P=0.001) and disease-free survival (P<0.001) in patients who received allogeneic HSCT. These findings were not found in the autologous HSCT. In a multivariate analysis of those who received allogeneic HSCT, prior treatment with ≥2 chemotherapy regimens (P=0.03) was independent predictor of lower OS. There were also trends noted toward lower OS for patients with documented infections at index admission or subsequent readmissions (P=0.09). CONCLUSIONS: More than 2 hospital readmissions within 6 months of allogeneic HSCT in CAYA, who are either heavily pretreated or had documented infections at index admission or subsequent readmissions adversely affected the outcomes.

Cerebral sinus venous thrombosis during childhood acute lymphoblastic leukemia therapy: Risk factors and management.

BACKGROUND: Cerebral sinus venous thrombosis (CSVT) is a rare but serious complication of childhood acute lymphoblastic leukemia (ALL) therapy. No available consensus exists regarding its risk factors and appropriate management due to the rarity of cases. PROCEDURES: Out of 209 ALL patients aged 1-21 years treated at the Children's Cancer Center of Lebanon between May 2002 and May 2015, 13 developed CSVT during therapy. Patient characteristics, clinical management, and outcomes were studied. RESULTS: The incidence of CSVT was 6.2% (95% confidence interval [CI]: 3.4-10.4). Using univariate analysis, increased risk of CSVT was observed with age >10 years (odds ratio [OR]: 3.56, 95% CI: 1.13-11.2), T-cell immunophenotype (OR: 4.14, 95% CI: 1.16-14.7), and intermediate/high risk disease (OR: 3.4, 95% CI: 1.03-11.7). The only statistically significant risk factor by multivariate analysis was the treatment as per the intermediate-/high-risk protocol (HR: 15.6, 95% CI: 1.43-171.3). Most cases (77%) occurred in the postinduction phases of treatment while receiving a combination of asparaginase and dexamethasone rather than prednisone. Treatment with low molecular weight heparin (LMWH) for a minimum of 3 months and until significant radiological improvement is observed resulted in 100% survival rate. All but one patient had complete neurological recovery. CONCLUSIONS: CSVT is an important complication of childhood ALL therapy. Postinduction combined asparaginase and dexamethasone intensive treatment for intermediate-/high-risk patients was the most important risk factor. Treatment with LMWH for a minimum of 3 months, and until asparginase therapy is over, with major radiological improvement seems to be effective and feasible.

Outcomes of children, adolescents, and young adults following allogeneic stem cell transplantation for secondary acute myeloid leukemia and myelodysplastic syndromes-The MD Anderson Cancer Center experience.

We conducted a retrospective analysis of outcomes for children and young adults with sAML/sMDS who underwent HSCT at our institution. Thirty-two patients (median age 20 years) with sAML (n=24) and sMDS (n=8) received HSCT between 1990 and 2013. The median time from sAML/sMDS diagnosis to HSCT was 4.1 months (range: 1.2-27.2 months). The transplant regimens were primarily busulfan based (n=19). BM was the primary donor source (n=15). Eleven recipients were transplanted with residual disease. At a median follow-up of 62.3 months (range: 0.4-250.9 months), 14 patients had disease recurrence. Acute GVHD, grade III/IV, occurred in three patients. Causes of death were as follows: disease relapse (n=12), infection (n=2), pneumonia (n=1), pulmonary hemorrhage (n=1), acute GVHD (n=1), and graft failure (n=1). A PS of ≥90% at the time of HSCT had a significant impact on PFS (P=.02). Patients achieving pretransplant primary CR (n=8) and those with sMDS and RA (n=6) had prolonged PFS (P=.04). On multivariate analysis, shorter time to transplantation (≤6 months from diagnosis of sAML/sMDS) was associated with superior OS (P=.0018) and PFS (P=.0005).