Approach to the Treatment of Expansile Metacarpal Aneurysmal Bone Cysts: A Report of Two Cases.

The two cases presented demonstrate the management of aneurysmal bone cysts of the metacarpal, which destroyed the normal bone architecture. Treatment of both cases included wide resection and metacarpal reconstruction with an intercalary fibular allograft. Denosumab use contrasts these two cases and is helpful in reestablishment of a cortical rim for fixation in the absence of a 1-cm margin proximally or distally to preserve the native carpometacarpal and metacarpophalangeal joints. Surgical resection and allograft reconstruction is a viable treatment for expansile metacarpal aneurysmal bone cysts, and neoadjuvant denosumab has utility in creating an ossified margin for fixation.

L-leucine improves anemia and growth in patients with transfusion-dependent Diamond-Blackfan anemia: Results from a multicenter pilot phase I/II study from the Diamond-Blackfan Anemia Registry.

BACKGROUND: Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by anemia, short stature, congenital anomalies, and cancer predisposition. Most cases are due to mutations in genes encoding ribosomal proteins (RP) leading to RP haploinsufficiency. Effective treatments for the anemia of DBA include chronic red cell transfusions, long-term corticosteroid therapy, or hematopoietic stem cell transplantation. In a small patient series and in animal models, there have been hematologic responses to L-leucine with amelioration of anemia. The study objectives of this clinical trial were to determine feasibility, safety, and efficacy of L-leucine in transfusion-dependent patients with DBA. PROCEDURE: Patients ≥2 years of age received L-leucine 700 mg/m2 orally three times daily for nine months to determine a hematologic response and any improvement in growth (NCT01362595). RESULTS: This multicenter, phase I/II study enrolled 55 subjects; 43 were evaluable. There were 21 males; the median age at enrollment was 10.4 years (range, 2.5-46.1 years). No significant adverse events were attributable to L-leucine. Two subjects had a complete erythroid response and five had a partial response. Nine of 25, and 11 of 25, subjects experienced a positive weight and height percentile change, respectively, at the end of therapy. CONCLUSIONS: L-leucine is safe, resulted in an erythroid response in 16% of subjects with DBA, and led to an increase in weight and linear growth velocity in 36% and 44% of evaluable subjects, respectively. Further studies will be critical to understand the role of L-leucine in the management of patients with DBA.

Switch to low-fat diet improves outcome of acute lymphoblastic leukemia in obese mice.

BACKGROUND: It is becoming increasingly recognized that weight and nutritional status can impact cancer survival. We have previously shown that obese mice with syngeneic acute lymphoblastic leukemia (ALL) have poorer response to chemotherapy treatment than control mice. We therefore investigated whether dietary intervention could improve outcome from the most common pediatric cancer, ALL. METHODS: Diet-induced obese (DIO) mice raised on a 60% calories from fat diet and control mice were implanted with syngeneic ALL cells. Some DIO mice were switched to the low-fat control diet. Survival from ALL was assessed without or with chemotherapy treatment starting at the time of the diet switch. Cells from DIO mice before and after diet switch were assessed by FACS for BrdU incorporation and phosphorylation status of AKT, S6K, and EIF2a. Similar experiments were done with human ALL xenografts. Mouse and human ALL cells were cultured in media with 10% or 5% fetal bovine serum, and sensitivity to chemotherapies assessed. RESULTS: DIO mice had poorer survival (17%) after vincristine monotherapy than control mice on a 10% low fat diet (42%; n = 12/group; p = 0.09, log rank). However, switching obese mice to the low-fat diet prior to initiation of vincristine led to dramatically improved survival (92%, p < 0.01 vs both other groups). In vitro, FBS restriction made murine and human ALL cells more sensitive to vincristine. Interestingly, while serum restriction enhanced ALL sensitivity to dexamethasone and l-asparaginase, dietary switch did not improve survival of DIO mice treated with either drug in monotherapy. Thus, it appears that dietary intervention has a unique effect to improve ALL cell sensitivity to vincristine in vivo. CONCLUSIONS: We report herein that a dietary intervention can improve ALL outcome in a preclinical model. Further work is needed to identify the mechanisms of this effect and investigate potential impact on human leukemia in patients.

Obesity is associated with residual leukemia following induction therapy for childhood B-precursor acute lymphoblastic leukemia.

Obesity is associated with poorer event-free survival (EFS) in pediatric acute lymphoblastic leukemia (ALL). Persistent minimal residual disease (MRD) in the bone marrow as measured by multidimensional flow cytometry (MDF) is a key early prognostic indicator and is strongly associated with EFS. We therefore hypothesized that obesity during induction would be associated with positive end-of-induction MRD (≥0.01%). We analyzed MDF of end-induction bone marrow samples from a historical cohort of 198 children newly diagnosed with B-precursor ALL (BP-ALL) and treated with Children's Oncology Group induction regimens. We assessed the influence of body mass index on risk for positive end-induction MRD in the bone marrow. In our cohort of BP-ALL, 30 children (15.2%) were overweight and 41 (20.7%) were obese at diagnosis. Independent of established predictors of treatment response, obesity during induction was associated with significantly greater risk for persistent MRD (odds ratio, 2.57; 95% confidence interval, 1.19 to 5.54; P = .016). Obesity and overweight were associated with poorer EFS irrespective of end-induction MRD (P = .012). Obese children with newly diagnosed BP-ALL are at increased risk for positive end-induction MRD and poorer EFS.