Atypical cause of prolonged myelosuppression

Abstract

We present the case of a 57-year-old male with poor prognosis (trisomy 21 and monosomy 7) acute myeloid leukaemia (AML) who presented with rigors and fever during cytogenetic remission. Peripheral and central line blood cultures were positive for Mycobacterium chelonae and he commenced empiric treatment with meropenem, amikacin, clarithromycin and ciprofloxacin. It appears that M chelonae infection was responsible for persistent myelosuppression after expected recovery from chemotherapy, which subsequently precluded optimum treatment for AML.

Background

Mycobacterium chelonae is a rapidly growing non-tuberculous mycobacterium commonly found in soil, water and dust. It can cause soft tissue or skeletal infection in healthy recipients, but disseminated disease is most frequently seen in the immunocompromised patient. Optimum treatment duration is not defined, but infection is most frequently treated for 12–18 months. M chelonae is frequently reported as causing infection in patients with cystic fibrosis and many leukaemias, but to date there are no reports of M chelonae infection occurring in adult patients with AML.

Case presentation

This patient, who had a background of chronic obstructive pulmonary disease (COPD), presented in June 2007 with a short history of fatigue and dyspnoea. A subsequent diagnosis of AML with multilineage dysplasia was made and cytogenetics showed the presence of trisomy 21 and monosomy 7. He received initial induction therapy with idarubicin and cytarabine (ARA-C) and following a stormy course, including the development of severe pneumonitis and respiratory failure, he entered complete morphologic and cytogenetic remission. Upon recovery, a second cycle of idarubicin and ARA-C was administered and he then went on to receive a subsequent single cycle of high dose ARA-C (HDAC). He did not have a histocompatible donor available and due to comorbidities, primarily COPD, he was not considered suitable for a matched unrelated transplant. Further consolidation chemotherapy was planned but due to prolonged myelosuppression following HDAC, this was deferred as he was heavily platelet and red cell transfusion dependent. During outpatient follow-up he complained of nocturnal rigors, occurring over a period of 3 weeks with associated lethargy. He denied fevers, sweats or anorexia. He became febrile 1 week later and was admitted for investigation.

Investigations

Blood cultures drawn in the outpatient clinic had grown an atypical mycobacterium (ATM). Following removal of the central line, culture of the tip grew ATM, and culture of the bone marrow aspirate (BMA) was negative in addition to a negative Ziehl-Nielssen stain. Peripheral blood cultures from this date were also positive for ATM. Computerised tomography of thorax, abdomen and pelvis showed no evidence of abscess. Subsequently, the ATM was identified as M chelonae with in vitro results indicating resistance to all antimicrobial agents tested.

Treatment

The microbiology and infectious disease services suggested removal of the central line, culture of bone marrow material and commencement of empiric intravenous treatment with meropenem and amikacin along with oral clarithromycin and ciprofloxacin. The patient was discharged on oral clarithromycin, linezolid and moxifloxacin and closely monitored as an outpatient for neutropenia. He had a repeat BMA which was negative for ATM on culture but did show evidence of trilineage dysplasia although there were <5% blasts. Given that he had persistent trilineage dysplasia in association with trisomy 7 (monosomy was no longer detectable), two further cycles of consolidation treatment with clofarabine were administered 16 weeks following commencement of continued treatment for ATM. This was well tolerated treatment without acute complication and he was able to complete a 6-month course of antimicrobial therapy without recurrence of ATM.

Outcome and follow-up

In spite of the in vitro sensitivities, our patient clinically improved without any change in therapy and had sterile follow-up blood cultures. Very interestingly, coinciding with the control of the ATM infection, there was considerable improvement in his blood counts and he became completely transfusion independent with his blood count at discharge having recovered to pre-infection levels. A subsequent BMA was negative for ATM (2 months after completion of antimicrobial treatment) but showed an increasing blast percentage (10%) with evidence of trilineage dysplasia and he then commenced treatment with 5-azacytidine. Seven months after completion of treatment he shows no evidence of recurrence of infection.

Discussion

M chelonae is a rapidly growing non-tuberculous mycobacterium commonly found in soil, water and dust. It can cause soft tissue or skeletal infection in healthy recipients, but disseminated disease is most frequently seen in the immunocompromised patient.¹ Due to its high proliferative rate it may be grown on culture within 1 week. Optimum treatment duration is not defined, but infection is most frequently treated for 12–18 months. M chelonae is frequently reported as causing infection in patients with cystic fibrosis,^2–4 erythroleukaemia,⁵ chronic lymphocytic leukaemia⁶ and paediatric acute non-lymphoblastic leukaemia,⁷ and in haematopoietic stem cell transplantation recipients⁸ (including catheter related infection),^9,10 cord blood stem cell transplantation recipients¹¹ and allogeneic bone marrow transplantation recipients.¹² It has also frequently been reported to cause fever in neutropenic patients.¹³ However, to date there are no reports of M chelonae infection occurring in adult patients with AML.

We present the case of a 57-year-old male with poor prognosis AML whose management was significantly disrupted by concurrent infection with M chelonae. It appears that ATM infection was responsible for persistent myelosuppression after expected recovery from chemotherapy during a period of cytogenetic remission, which subsequently precluded optimum treatment for AML. Treatment of this infection is typically for 18 months, but in this case the treatment period could be shortened as the apparent focus of infection (central line) was promptly removed. There was no evidence of recurrence of infection despite this shortened duration of therapy. We suggest vigilance for atypical infections in patients with known remission but persistent myelosuppression, and consideration of early removal of potential foci of infection such as central venous catheters.

Learning points

• Atypical mycobacterium may cause profound myelosuppression and should be considered in patients after chemotherapy.

• When identified, sources of infection (eg, central lines) must be removed as soon as possible.

• Expert care is required in immunocompromised patients, with close input from the medical microbiology and infectious disease departments.