B-cell acute lymphoblastic leukemia and juvenile xanthogranuloma in a patient with ETV6 thrombocytopenia and leukemia predisposition syndrome: novel clinical presentation and perspective.

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Systematic review and meta-analysis of objective and subjective quality of life among pediatric, adolescent, and young adult bone tumor survivors.

BACKGROUND: Pediatric, adolescent, and young adult survivors of bone sarcomas are at risk for poor quality of life (QOL). We conducted a systematic review and meta-analysis to summarize the literature describing QOL in this population and differences in QOL based on local control procedures. PROCEDURE: Included studies described ≥5 patients <25 years old who had completed local control treatment for bone sarcoma, defined QOL as a main outcome, and measured it with a validated instrument. Data extraction and quality assessments were conducted with standardized tools. Meta-analyses compared QOL based on surgical procedure (limb-sparing vs. amputation) and were stratified by assessment type (objective physical function, clinician-assessed disability, patient-reported disability, and patient-reported QOL). Effect sizes were reported as the standard mean difference when multiple instruments were used within a comparison and weighted mean difference otherwise. All were weighted by inverse variance and modeled with random effects. RESULTS: Twenty-two of 452 unique manuscripts were included in qualitative syntheses, eight of which were included in meta-analyses. Manuscripts were heterogeneous with respect to included patient populations (age, tumor type, time since treatment) and QOL instruments. Prospective studies suggested that QOL improves over time, and that female sex and older age at diagnosis are associated with poor QOL. Meta-analyses showed no differences in outcomes between patients who underwent limb-sparing versus amputation for local control. CONCLUSION: QOL studies among children and AYAs with bone sarcoma are remarkably diverse, making it difficult to detect trends in patient outcomes. Future research should focus on standardized QOL instruments and interpretations.

Diagnosis and management of cutaneous lymphomas and lymphoid proliferations in children, adolescents and young adults (CAYA).

Cutaneous lymphomas and lymphoid proliferations (LPD) in children, adolescents, and young adults (CAYA) are a heterogeneous group of lymphoid neoplasms that present formidable diagnostic challenges to clinicians and pathologists alike. Although rare overall, cutaneous lymphomas/LPD occur in real-world settings and awareness of the differential diagnosis, potential complications, and various therapeutic approaches will help ensure the optimal diagnostic work-up and clinical management. Lymphomas/LPD involving the skin can occur as primary cutaneous disease in a patient that characteristically has lymphoma/LPD confined to the skin, or as secondary involvement in patients with systemic disease. This review will comprehensively summarize both primary cutaneous lymphomas/LPD that occur in the CAYA population as well as those CAYA systemic lymphomas/LPD with propensity for secondary cutaneous involvement. Focus on the most common primary entities occurring in CAYA will include lymphomatoid papulosis, primary cutaneous anaplastic large cell lymphoma, mycosis fungoides, subcutaneous panniculitis-like T-cell lymphoma, and hydroa vacciniforme lymphoproliferative disorder.

An 8-Year-Old Boy With Prolonged Fever and Subcutaneous Nodules.

An 8-year-old boy with asthma presented with prolonged fever, malaise, extremity weakness, polyarthralgias, malar rash, and subcutaneous nodules. Physical examination was remarkable for a faint malar rash, flesh-colored papules on the dorsal aspect of the fingers, arthritis of multiple joints in the hands, and subcutaneous nodules. The nodules were firm, nontender, and distributed over multiple extremities and the trunk. The patient was admitted to expedite workup. Initial laboratory test results revealed leukopenia, mild elevation of the aminotransferases, an elevated erythrocyte sedimentation rate, and normal level of creatine kinase. His echocardiogram was normal. Infectious disease studies were negative. Additional examination revealed dilated capillaries in his nail beds and bilateral hip weakness. MRI of his extremities was negative for myositis or calcification of the nodules. We obtained a biopsy of the subcutaneous nodules, and because the patient remained afebrile during the hospitalization, we discharged him from the hospital with outpatient follow-up. Our expert panel reviews the course of the patient's evaluation and investigation, as well as the implications of his diagnosis based on the tissue pathology from the nodule biopsy.

Antibody-Drug Conjugates for the Treatment of Acute Pediatric Leukemia.

The clinical development of antibody-drug conjugates (ADCs) has gained momentum in recent years and these agents are gradually moving into frontline regimens for pediatric acute leukemias. ADCs consist of a monoclonal antibody attached to a cytotoxic payload by a cleavable linker. This structure allows for highly cytotoxic agents to be directly delivered to leukemia cells leading to cell death and avoids excessive off-tumor toxicity. Near universal expression on B-cell acute lymphoblastic leukemia (ALL) blasts and the ability of rapid internalization has rendered CD22 an ideal target for ADC in B-ALL. Inotuzumab ozogamicin, the anti-CD22 antibody linked to calicheamicin led to complete remission rates of 60-80% in patients with relapsed/refractory B-ALL. In acute myeloid leukemia (AML), the CD33 targeting gemtuzumab ozogamicin has demonstrated modest improvements in survival and is the only ADC currently licensed in the United States for pediatric patients with de novo AML. Several other ADCs have been developed and tested clinically for leukemia but have achieved limited success to date. The search for additional leukemia-specific targets and optimization of ADC structure and specificity are ongoing efforts to improve their therapeutic window. This review provides a comprehensive overview of ADCs in acute leukemias, with a focus on pediatric ALL and AML.

CBFB-MYH11 fusion neoantigen enables T cell recognition and killing of acute myeloid leukemia.

Proteins created from recurrent fusion genes like CBFB-MYH11 are prevalent in acute myeloid leukemia (AML), often necessary for leukemogenesis, persistent throughout the disease course, and highly leukemia specific, making them attractive neoantigen targets for immunotherapy. A nonameric peptide derived from a prevalent CBFB-MYH11 fusion protein was found to be immunogenic in HLA-B*40:01+ donors. High-avidity CD8+ T cell clones isolated from healthy donors killed CBFB-MYH11+ HLA-B*40:01+ AML cell lines and primary human AML samples in vitro. CBFB-MYH11-specific T cells also controlled CBFB-MYH11+ HLA-B*40:01+ AML in vivo in a patient-derived murine xenograft model. High-avidity CBFB-MYH11 epitope-specific T cell receptors (TCRs) transduced into CD8+ T cells conferred antileukemic activity in vitro. Our data indicate that the CBFB-MYH11 fusion neoantigen is naturally presented on AML blasts and enables T cell recognition and killing of AML. We provide proof of principle for immunologically targeting AML-initiating fusions and demonstrate that targeting neoantigens has clinical relevance even in low-mutational frequency cancers like fusion-driven AML. This work also represents a first critical step toward the development of TCR T cell immunotherapy targeting fusion gene-driven AML.