What is the treatment approach for a patient with leukemia and latent tuberculosis (TB)?

From the Guidelines

Treating a leukemic patient with latent tuberculosis requires initiating treatment with a preferred rifamycin-based regimen, such as 3 months of once-weekly isoniazid plus rifapentine, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin, to prevent TB reactivation and minimize hepatotoxicity risk 1. The recommended approach is to initiate latent tuberculosis infection (LTBI) treatment before or concurrently with leukemia therapy to prevent TB reactivation.

• The preferred regimens are based on effectiveness, safety, and high treatment completion rates, as outlined in the 2020 guidelines from the National Tuberculosis Controllers Association and CDC 1, 2.
• Alternative regimens, such as daily isoniazid for 6 or 9 months, are available but have higher toxicity risk and lower treatment completion rates than the preferred rifamycin-based regimens.
• Before starting treatment, baseline liver function tests should be obtained and monitored regularly, as both TB medications and chemotherapy can cause hepatotoxicity.
• Drug interactions between TB medications (especially rifampin) and chemotherapeutic agents must be carefully managed, as rifampin can induce liver enzymes and reduce the efficacy of many cancer drugs.
• Pyridoxine (vitamin B6) supplementation at 25-50mg daily should be added to prevent peripheral neuropathy when using isoniazid.
• The timing of TB treatment is crucial - ideally, LTBI treatment should be started 2-3 weeks before chemotherapy when possible, but in urgent cases of acute leukemia requiring immediate treatment, both therapies can be initiated simultaneously with close monitoring 3. This approach is necessary because leukemia treatment causes immunosuppression that significantly increases the risk of TB reactivation, which could be life-threatening in these vulnerable patients.

From the FDA Drug Label

For preventive therapy of tuberculous infection and treatment of tuberculosis, it is recommended that physicians be familiar with the following publications: For Treatment of Tuberculosis Isoniazid is used in conjunction with other effective anti-tuberculosis agents. The above treatment guidelines apply only when the disease is caused by organisms that are susceptible to the standard antituberculous agents Rifampin is indicated in the treatment of all forms of tuberculosis. A three-drug regimen consisting of rifampin, isoniazid, and pyrazinamide is recommended in the initial phase of short-course therapy which is usually continued for 2 months

The treatment of a leukemic patient with latent tuberculosis should be individualized and based on susceptibility studies.

• Key considerations:
  • The patient's immune status due to leukemia
  • The potential for drug interactions between antitubercular and antileukemic medications
  • The need for close monitoring of the patient's condition and potential side effects
• Treatment options:
  • A combination of isoniazid and rifampin may be used, with the addition of other anti-tubercular agents as needed
  • The treatment regimen should be adjusted based on the patient's response to therapy and the results of susceptibility testing 4, 5 It is essential to consult with an expert in tuberculosis and hematology to determine the best course of treatment for the patient.

From the Research

Treatment Options for Latent Tuberculosis Infection

• Isoniazid (INH) has been the mainstay of treatment for latent tuberculosis infection for almost 50 years, with a recommended regimen of 9 months daily self-administered INH (9H) having an efficacy of more than 90% if completed properly 6
• However, INH is associated with serious adverse events, including hepatotoxicity, which can be fatal, and close follow-up of patients is necessary, increasing the cost and complexity of treatment 6
• Alternative regimens, such as 2 months of rifampin and pyrazinamide, have excellent efficacy in experimental studies, but are associated with an unacceptably high rate of severe liver toxicity in non-HIV-infected adults 6
• Three to four months of INH and rifampin has had equivalent effectiveness as 6 months INH in several randomized trials, but completion of therapy and toxicity has been the same as with INH 6
• Four months of rifampin has been found to have significantly better completion than 9H, with significantly less toxicity, especially hepatotoxicity 6, 7

Treatment Completion and Hepatotoxicity

• Treatment completion rates were higher for 4 months rifampin (53.5%) than for 9 months isoniazid (36.9%), with an adjusted relative risk of 1.5 (95% CI: 1.3-1.7) 7
• Severe hepatotoxicity risk was higher with isoniazid (n=15) than rifampin (n=1), with an adjusted odds ratio of 2.3 (95% CI: 0.3-16.1) 7
• Patients without co-morbidities had lower hepatotoxicity risk (0.1% versus 1.0%) 7

Novel Treatment Regimens

• Once-weekly isoniazid plus rifapentine for 3 months has been shown to be as effective as 9 months of isoniazid alone in preventing tuberculosis, with a higher treatment-completion rate 8
• Daily rifampin for 4 months, and daily isoniazid plus rifampin for 3-4 months, are also effective treatment regimens for latent tuberculosis infection 9
• Novel vaccine strategies, host immunity-directed therapies, and ultrashort antimicrobial regimens for TB prevention are under evaluation 9