At the University of Nebraska, we adhere to current guidelines advocating MMR vaccination at 24 months after autologous or allogeneic stem cell transplant in patients without chronic graft-vs-host disease or ongoing immune suppression. Earlier MMR vaccination may be advised in a measles outbreak setting, but data are limited in stem cell transplant recipients.
—Alison G. Freifeld, MD
Measles outbreaks in the United States during 2014 and early 2015 have yielded an unprecedented number of cases nationwide, raising concerns about the threat measles poses to cancer patients (especially children) who may be at risk for severe complications and even death due to measles infection.
“In normal children, measles is an acute viral respiratory illness characterized by a prodrome of high fever with cough, coryza, and conjunctivitis, known as ‘the three C’s,’ followed by the evolution of a pathognomonic enanthema (Koplik spots) in the oropharynx and a diffuse red maculopapular rash. Measles pneumonitis is the most feared complication, and it is associated with a high rate of mortality. As many as 1 in 20 children with measles may develop lung infection.” Alison G. Freifeld, MD, who specializes in infectious diseases in cancer patients, said in an interview with The ASCO Post. Dr. Freifeld is Professor in the Department of Internal Medicine at the University of Nebraska Medical Center, Omaha.
“Measles encephalitis is also rare, occurring in 1 out of 1,000 cases, which can lead to seizures and mental deterioration. More common complications include otitis media, bronchopneumonia, laryngotracheobronchitis, and diarrhea,” Dr. Freifeld said.
Children With ALL at Risk
“In 2000, measles was declared eliminated in the United States. Since then, measles cases have ranged from as few as 37 in 2004 to 644 in the 2014 outbreak. The majority of cases have been among people who are not vaccinated against measles. Concerns now abound regarding the vulnerability of children with cancer who may contract the infection,” Dr. Freifeld said.
“Prior to 2000, children with acute lymphocytic leukemia (ALL), in particular, were reported to develop severe and often fatal measles pneumonia.1 Children with ALL seem to be at particular risk for severe measles, due to the more frequent loss of protective antibodies postchemotherapy compared with childen who have other cancers.2 Profound chemotherapy-induced B-cell depletion may be linked to the measles risk,” she continued.
“The most effective way to protect children with ALL is to ensure timely vaccination of their family members and community contacts with measles, mumps, rubella (MMR) vaccine. No case of vaccine strain virus transmission to cancer patients has ever been reported,” she noted.
Stem Cell Transplant Recipients and Measles Vaccine
In a majority of stem cell transplant recipients, antigen-specific antibody titers, including those for measles, decline progressively over time posttransplant. Accordingly, a fixed schedule of vaccination is prescribed for all autologous and allogeneic stem cell transplant recipients. MMR and other live virus vaccination is not recommended until patients are considered immunologically competent: at least 2 years post–allogeneic transplant, off immunosuppression, and free of chronic graft-vs-host disease.3
During a measles outbreak in Brazil, 34 stem cell transplant patients not on immunosuppression were safely immunized between 1 and 2 years posttransplant, raising the question of whether this vaccine should be given earlier than 2 years in general. “Early vaccination with MMR would be of interest to explore in a multicenter protocol,” said Dr. Freifeld. “Determining if MMR is safe and immunogenic in some populations of post–stem cell transplant patients—for example autologous recipients—could be beneficial,” she commented.
“Currently at the University of Nebraska transplant program, we assess measles titers for post–stem cell transplant patients seen for 1- and 2-year follow-up visits but are not performing active surveillance. We adhere to the current [American Society for Blood and Marrow Transplantation/Infectious Diseases Society of America] guidelines to reserve MMR for patients out 2 years or more from stem cell transplant. However, if measles activity becomes more widespread in our region, we may need to consider early vaccination in some of our seronegative transplant patients who are out more than 1 year. Two MMR injections at least 2 months apart would be recommended to promote adequate responses,” stated Dr. Freifeld.
‘Hallmark’ Measles Rash May Not Develop
Although a diffuse bright red maculopapular rash is characteristic of measles virus disease, as many as 30% of immunocompromised patients do not develop a rash.1 Identifying these patients is challenging and depends on clinical and epidemiologic clues. Children being treated for ALL and other immunocompromised cancer patients who have unexplained pneumonitis or encephalitis should be tested for measles virus, if active cases have been confirmed in the region.
“That makes it a real challenge,” Dr. Freifeld acknowledged, “because the rash, of course, is the hallmark of measles, and it is what we depend upon to make the diagnosis clinically. Evaluating whether family members or schoolmates have had a measles-like rash or illness may also be helpful. The patient should have serum IgM and IgG antibodies sent to assess immune status, and real-time polymerase chain reaction [RT-PCR] can identify the measles virus RNA in blood or bronchoscopy fluid for rapid diagnosis,” she said.
“Laboratory confirmation is essential for all sporadic measles cases and all outbreaks. Detection of measles-specific IgM antibody and measles RNA by RT-PCR are the most common methods for confirming measles infection,” according to the Centers for Disease Control and Prevention (CDC). Health-care providers should obtain “both a serum sample and a throat swab (or nasopharyngeal swab) from patients suspected to have measles at first contact with them. Urine samples may also contain virus, and when feasible to do so, collecting both respiratory and urine samples can increase the likelihood of detecting measles virus.”4
There is no drug therapy for measles, Dr. Freifeld noted, only supportive care.
According to the CDC, immunoglobulin should be administered to people who have been exposed to measles and are at risk for severe illness and complications from measles. This includes people with severely compromised immune systems, who do not yet have onset of measles symptoms.
“It would absolutely be a good idea to give immunoglobulin” to patients with cancer who have been exposed to measles but do not have symptoms, Dr. Freifeld said. She cited a study from the Cochrane Database that found that the risk of measles was up to 83% lower for nonimmune people receiving intramuscular or intravenous immunoglobulin within 7 days of exposure to measles.5 The investigation included 1 randomized trial, 2 quasirandomized trials, and 10 cohort studies involving a total of 3,925 participants. ■
Disclosure: Dr. Freifeld reported no potential conflicts of interest.
1. Kaplan LJ, Daum RS, Smaron M, et al: Severe measles in immunocompromised patients. JAMA 267:1237-1241, 1992.
2. Bochennek K, Allwinn R, Langer R, et al: Differential loss of humoral immunity against measles, mumps, rubella and varicella-zoster virus in children treated for cancer. Vaccine 32:3357-3361, 2014.
3. Rubin LG, Levin MJ, Ljungman P, et al: 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 58:309-318, 2014.
4. Centers for Disease Control and Prevention: Measles (rubeola): For healthcare professionals (updated February 9, 2015). Available at www.cdc.gov/measles/hcp/. Accessed February 11, 2015.
5. Young MK, Nimmo GR, Cripps AW, et al: Post-exposure passive immunisation for preventing measles. Cochrane Database Syst Rev 4:CD010056, 2014.
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