Deepak Chellapandian, M.D., was a resident medical student in Philadelphia when he developed a fascination with diseases related to over-production of a kind of white blood cells known as histiocytes that can lead to organ damage and tumor formation.
“Histiocytosis is one of my areas of passion right from the beginning,” says Chellapandian, who joined the Johns Hopkins All Children’s Cancer & Blood Disorders Institute as a blood and marrow transplant specialist in 2017. “I became intrigued with this disease and wanted to do further work on it.”
Chellapandian continued to build his expertise through fellowships, presented numerous abstracts in the national and international meetings and has published several papers related to histiocytic disorders, which are known as orphan diseases because they affect fewer than 1 in 200,000 children. His latest work, in collaboration with researchers from North America, Europe and China, was published in December by Cancer, an international interdisciplinary reputable journal of the American Cancer Society.
“A Multicenter Study of Patients with Multisystem Langerhans Cell Histiocytosis Who Develop Secondary Hemophagocytic Lymphohistiocytosis” reports the results of a retrospective clinical study that looks at patients who have the rare blood disorder Langerhans cell histiocytosis (LCH). The cell normally helps fight infection, but in some cases, the body accumulates too many of the immature cells. The study looks at a subset of patients who also developed another rare blood disorder of the immune system, hemophagocytic lymphohistiocytosis (HLH) and falls under the same spectrum of histiocytic disorders. The study concludes that patients with LCH-associated HLH have poorer outcomes than LCH patients who do not develop HLH. It suggests further study to enhance recognition of LCH-associated HLH and to optimize treatment of it.
“LCH is a very interesting disorder,” Chellapandian says. “The most common presentation is in the bone and skin. Those are usually less harmful and easily treatable. The one that has the highest risk of complications is the multisystem presentation where these abnormal LCH cells go into the ‘risk organs’ such as liver, spleen and bone marrow. There are treatment options for these patients, but the outcomes aren’t very good.”
The Study’s Findings
For the study published in Cancer, Chellapandian and the other researchers compiled data on 384 LCH patients between 2000 and 2015. They believe it to be the largest study conducted on the disorder outside the context of a clinical trial. They found that 32 of these patients met the diagnostic criteria for HLH.
“To our surprise, we found the association was not that rare,” Chellapandian says. “We found it in nine to 10 percent of the patients. This coexistence is not being well reported in the literature. Almost one-third of these patients had associated infections, which may have triggered the development of HLH. That’s one of the conclusions we made in this paper.”
The study suggests young girls with multisystem LCH disease involving “risk organs” and those that do not have LCH involvement of the bones early on are at greater risk to develop HLH.
“It turns out to be that development of HLH in LCH disease dictates a bad outcome and increases the chances of dying from the disease, which is a very unique finding of the study,” Chellapandian says.
Building a Program
Chellapandian, who is originally from Madurai, India, is building a program at Johns Hopkins All Children’s to continue and expand his research and to treat more histiocytosis patients. The hospital is an associate member of the North American Consortium for Histiocytosis (NACHO), which supports clinical and translational studies and biological research for histiocytic diseases. NACHO launches a clinical study called LCH-IV this month, seeking to better tailor treatment in children.
“The usefulness of this consortium is it opens avenues for more research and to have access for several protocols to treat these disorders, both LCH and HLH,” Chellapandian says.
Chellapandian sees many promising areas for HLH, including gene therapy and unique transplant options with 50 percent match donors. He is eager to work with the Histiocytosis Association and other researchers to help in those advancements.
“When I came to Johns Hopkins All Children’s, I was very impressed with their research infrastructure here, especially the amount of investment they’ve made,” he says. “I can see myself growing with the research in this place and how the future will be. One of the areas I’m looking at is getting more referrals for transplant for patients with these rare forms of blood diseases and expanding transplant options for them using half-matched family donors. Also, the future seems promising with gene therapy. It’s on the horizon, at least for certain rare genetic diseases including, familial HLH.
“I think the future of our histiocytosis program in collaboration with the international consortium will bring more opportunities in the future. My goal is to make it a center of excellence in treating patients with this disorder and develop more novel transplant options for these patients who have been lacking donors. These are some promising areas in the future.”
What is LCH?
Langerhans cell histiocytosis (LCH) generally occurs between ages 1 and 3 when the body accumulates too many immature Langerhans cells. These white blood cells normally help the body fight infection, but a buildup of too many in certain parts of the body can lead to tumors or organ damage, according to the Histiocytosis Association.
The cause of LCH is unknown, but symptoms include skin rash, bone lesions, lung, liver or spleen dysfunction, or ear infections. It is believed to affect fewer than one in 200,000 children and is not contagious. Some cases of LCH do not require treatment, but a hematologist-oncologist should determine whether chemotherapy is necessary.
What is HLH?
Hemophagocytic lymphohistiocytosis (HLH) primarily affects infants and young children. It is a rare disorder of the immune system and can be hereditary (“primary”) or associated with infections, viruses, autoimmune diseases and cancers (“secondary”), according to the Histiocytosis Association. The hereditary form, sometimes called familial hemophagocytic lymphohistiocytosis (FHLH or FHL), may occur when defective genes are inherited from the mother or from both parents.
Symptoms include persistent high fever, liver and spleen dysfunction, sudden blindness, skin rash, coordination problems, seizures and enlarged lymph nodes. Treatment may include chemotherapy, immunotherapy, steroids, antibiotics, antiviral drugs, or bone-marrow or stem-cell transplants.