A child with acute myeloid leukemia complicated by calcaneal osteomyelitis due to Mycobacterium abscessus infection after induction chemotherapy successfully salvaged with bedaquiline and clofazimine. (February 2021)

• Record Type: Journal Article
• Authors: Chan, Wilson Yau-Ki; Ho, Pak-Leung; To, Kelvin Kai-Wang; Lam, Albert Ying-Lee; Ho, Kenneth Wai-Yip; Lau, Tak-Wing; So, Noah Lok-Wah; Ha, Shau-Yin
• Is Part Of: International journal of infectious diseases. Volume 103(2021)
• Page Start: 9
• Page End: 12
• Publication Date: 2021-02
• Subjects: AFB Acid-fast bacilli -- AML Acute myeloid leukemia -- CT Computed tomography -- HSCT Hematopoietic stem cell transplantation -- I&D Incision and drainage -- IFN-γ Interferon-gamma -- IV Intravenous -- LN Lymph node -- MRD Minimal residual disease -- MRI Magnetic resonance imaging -- MTBC Mycobacterium tuberculosis complex -- NTM Non-tuberculous mycobacteria -- PET Positive emission tomography; leukemia -- osteomyelitis -- non-tuberculous Mycobacteria; Communicable diseases -- Periodicals; Communicable Diseases -- Periodicals; Communicable diseases; Periodicals; Electronic journals; 616.9
• DOI: 10.1016/j.ijid.2020.10.102
• Languages: English
• ISSNs: 1201-9712

Abstract

Graphical abstract: Timeline of events from initiation of chemotherapy treatment to time of publication #1Course 1 induction chemotherapy (MEC) with mitoxantrone 25 mg/m 2, etoposide 750 mg/m 2 and cytarabine 2800 mg/m 2 administered. #2Course 2 induction chemotherapy (ADxE) with cytarabine 1400 mg/m 2, daunorubicin 180 mg/m 2, and etoposide 450 mg/m 2 administered. #3Oral thioguinine 120 mg/m 2 daily was given for total of 18 days (intended for total of 28 days in a 4-week cycle), IV cytarabine 75 mg/m 2 daily was given on Days 1–4 and 15–18 of the 4-weekly cycle (a total of eight doses were given and then withheld due to infection). A single dose of IT cytarabine 40 mg was given 1 day prior to start of the 4-week cycle of chemotherapy. ○1Day 29 marrow confirmed remission status with MRD < 0.1% ○2Day 40 marrow before course-2 induction chemotherapy continued in remission with MRD < 0.1% ○3Bone marrow aspiration performed 2 weeks after completion of one course of low-dose bridging chemotherapy (prior to consideration of starting consolidation chemotherapy) confirmed persistent remission status with MRD < 0.1% ○4Regular 4-weekly bone marrow aspiration confirmed remission with MRD < 0.1% ○5Regular 4-weekly bone marrow aspiration confirmed remission with MRD < 0.1% ◼1MRI of right lower limb revealed bilateral shotty groin lymph nodes (LNs), largest 1.6 cm at the right groin and 1 cm at the right popliteal fossa, accompanied with subcutaneous edema over the right upper medial and posterior distal thigh ( Figure 1 A) . Neutrophil and monocyte counts were always less than 1 × 10 9 /L and 0.2 × 10 9 /L, respectively. ◼2MRI of the groin and right ankle showed abscess at the right groin and lateral aspect of the right ankle with underlying osteomyelitis of calcaneus ( Figure 1 B) . ◼3MRI of bilateral lower limbs showed interval improvement in inflammatory changes over the bilateral femur, tibia, and right calcaneus ◼4MRI of hips showed mild synovitis ◼5MRI of the right ankle showed minimal residual inflammatory changes at the right calcaneus BxUltrasound-guided aspiration and biopsy were performed, which yielded granulomas with surrounding suppurative inflammation ( Figure 1 C) . A moderate number of AFB was highlighted on aspirate sample. Neutrophil and monocyte counts recovered. ◆1PET-CT showed abscesses in right posterior thigh and popliteal fossa (maximum standard uptake value [SUVmax ] 3.8), right calcaneal osteomyelitis (SUVmax 9.4), as well as multiple hypermetabolic LN at the right groin (SUVmax 6.5) extending to the right internal iliac LN ( Figure 1 D) . ◆2PET-CT showed worsening of the right calcaneal osteomyelitis with increased bony lysis ◆3PET-CT showed residual infective focus at the right calcaneus with interval reduction in metabolic activity over the right groin and right popliteal fossa ◆4PET-CT showed resolution of right groin lymphadenopathy and right popliteal fossa subcutaneous lesion, also decreased metabolic activity at the right calcaneus §1First operation on calcaneal bone excision and debridement of the right ankle §2Second operation involving I&D of the right groin and popliteal abscesses along with debridement of the right ankle soft tissue §3Third operation on sequestrectomy of the right calcaneus and insertion of antibiotic-infused cement (vancomycin, amikacin, and gentamycin) §4Fourth operation on removal of antibiotic-infused cement and bone graft insertion. Highlights: Long-term disease remission achieved without relapse for 2 years. Only two cycles of induction chemotherapy with one cycle of low-dose chemotherapy. Successful treatment of patient using two drugs with limited data in the pediatric population (bedaquiline and clofazimine) when the patient was intolerable to first-line anti-mycobacterial agents. Successful clearance of right calcaneal osteomyelitis and subcutaneous abscesses with multiple operations and antibiotic-infused cement. Normal limb function and activities. Abstract: Our patient was a 4-year-old female with acute myeloid leukemia complicated with right calcaneal osteomyelitis due to Mycobacterium abscessus with subcutaneous abscesses extending to the popliteal and groin regions after two courses of induction chemotherapy according to NOPHO-AML 2012 protocol. She required multiple operations and prolonged anti-mycobacterial therapy. A high index of suspicion for mycobacterial infection is required for immunocompromised patients with prolonged fever or unusual presentation. Mycobacterial osteomyelitis is rare, difficult to diagnose and treat, and may necessitate prolonged interruption of anti-leukemic therapy. Multidisciplinary collaboration in patient management is crucial. Long-term toxicity of antimicrobials with uncertain efficacy should not be overlooked.