Co-Administration of Trimethoprim-Sulfamethoxazole during High-Dose Methotrexate - Haematologic Side Effects?

Introduction:

While High-dose Methotrexate (HDMTX) is part of several chemotherapeutic regimens, Trimethroprim-Sulfamethoxazole (TMP/SMX) is commonly used to prevent Pneumocysits-jiroveci pneumonia, in immunocompromised patients. Since these drugs are folate antagonists, co-administration is not recommended to avoid cumulative toxicity. We explored haematologic effects of co-administration of HDMTX and TMP/SMX.

Methods:

Consolidation therapy for acute lymphoblastic leukaemia include four courses of HDMTX (5000mg/m²/d intravenously) together with daily 6-Mercaptopurine (50mg/m² orally). For Pneumocystis-pneumonia-prophylaxis, patients receive either TMP/SMX 5mg/kg/d (based on TMP component) p.o. for 3 or 4 days weekly or Pentamidine 300mg by inhalation once monthly.

We retrospectively compared blood count parameters before and 14 days after HDMTX-administration (Wilcoxon-Test) as well as relative changes of these parameters between patients with and without TMP/SMX prophylaxis (Mann-Whitney-U-Test).

Results:

We analyzed 112 HDMTX-episodes in 28 patients (1.4 to 19.1; median 5.4 years old; 42.9% female.).

Compared to baseline parameters at HDMTX-administration, 14 days thereafter we observed widely spread changes of the white blood count (WBC, -78.4 to +251.8; median -6.7%), absolute neutrophil count (ANC, -85.5 to +406.2; median -12.6%), lymphocytes (Ly, -94.8 to +161.4; median -5.0%), thrombocytes (Thr, -78.5 to +173.2; median -13.2%) and haemoglobin (Hb, -32.3 to +44.1; median +3.8%). The WBC (p=0.003), ANC (p=0.029) and Thr (p<0.001) were significant lower and Hb (<0.001) was significant higher as prior to HDMTX-administration. Difference of lymphocytes was not significant.

Comparing episodes with TMP/SMX-prophylaxis (n=51) and with Pentamidine-prophylaxis (n=61), relative changes showed no significant differences for any of the tested parameters.

Discussion:

While most parameters decreased after HDMTX (additionally caused by 6-Mercaptopurine co-administration), co-administration of TMP/SMX seems to have no significant influence on these changes.

Thus, our results do not support the recommendation to avoid co-administration of HDMTX and TMP/SMX.