Treatment With Combination Chemotherapy (chop) Causes Deleterious Effects On Muscle Mass In Juvenile Mice

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Pediatric non-Hodgkin lymphoma (NHL) is a common childhood cancer. While combination chemotherapy (chemo) regimens like CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone) have significantly improved survival rates, they often induce adverse side effects. Although muscle atrophy is a well-recognized consequence of cancer therapy, the acute impact of common pediatric chemo like CHOP on skeletal muscle in young patients remains poorly understood. PURPOSE: To address this knowledge gap, we investigated the acute effects of CHOP chemo on skeletal muscle mass in a juvenile mouse model. METHODS: Male and female C57BL/6 J mice (N = 9-11/group) were treated with two cycles of CHOP or Vehicle (Veh) beginning at 28 days of age. Each cycle consisted of a single CHOP or Veh injection followed by four daily prednisone or Veh injections. A 5-day recovery separated the two cycles. After the second cycle/recovery period, muscles were collected for analysis. Data were analyzed using a two-way ANOVA (Sex x Chemo) and data presented as means ± standard error. RESULTS: Chemo treatment resulted in lower body weights (main effect (ME) of chemo p < 0.001) in both males (Veh = 20.85 ± 0.33 g vs CHOP = 18.41 ± 0.37 g) and females (Veh = 16.57 ± 0.39 g vs CHOP = 15.61 ± 0.37 g). There was also a significant ME of sex (p < 0.001) for all muscles masses, with females having lower muscle mass compared to males. Chemo treatment also caused lower muscle masses in gastrocnemius (ME p < 0.001), plantaris, (ME p = 0.001), and soleus (ME p < 0.032) with no significant interactions. Because the mice are actively growing, we calculated muscle mass relative to tibia length. There was no significant interaction (p = 0.80) or main effects (sex p = 0.84, chemo p = 0.11) on tibia length. An important finding is that even when controlling for body size in gastrocnemius to tibia ratio, there was a main effect of chemo treatment (p < 0.01) in both males (Veh = 6.00 ± 0.21 mg/mm vs CHOP = 4.91 g/mm ± 0.23) and females (Veh = 4.31 ± 0.26 g/mm vs CHOP = 3.94 ± 0.24 g/mm). CONCLUSIONS: These data indicate that treatment with CHOP resulted in similar effects on males and female juvenile mice causing significantly lower body and muscle masses. These results align with literature on chemotherapy effects on adult mice and future studies will look at the mechanisms causing reduced muscle mass.

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