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By
Kenneth McClain, M.D., Ph.D.
Langerhans cell histiocytosis (LCH) is one of the rare diseases
seen by pediatric oncologists that in the past was treated by
several different methods
–
from surgery alone to radiation
therapy and several types of chemotherapy.
Many investigators are unaware of the organized clinical trials
sponsored by the Histiocyte Society (HS). The trials have
provided important data on efficacy of the best medications
available, but more importantly have taught us about the
long-term consequences of LCH, especially regarding central
nervous system disease associated with skull lesions of the
orbit, mastoid and temporal bone. These lesions must be treated
with velban and prednisone for at least six months to reduce the
risk of developing diabetes insipidus from 40 percent to 20
percent. The next treatment study will have to address how to
further reduce this risk.
Another recent discovery is that pulmonary disease in children
may not be a high-risk organ as has classically been taught.
For years, LCH of the liver, spleen, bone, marrow and lung has
been classified as needing more vigorous treatment than that of
bone, skin or lymph node. Published evidence now exists that
shows children with pulmonary disease – with or without the
low-risk sites – have better chances of cure than those with
other high-risk organs.
Recently, a nearly 2-year-old patient with pulmonary, liver and
spleen LCH had a remarkable response in her lungs to a new
chemotherapy plan. The patient had not responded well to initial
treatment with vinblastine, prednisone and methotrexate at
another hospital during the first months of 2005. I consulted with the patient’s physicians
and recommended
treatment with 2-CdA (Cladribine) and cytosine arabinoside.
After two courses, the patient improved, but her lungs were so
badly affected that a lung transplant became necessary.
The patient transferred to Texas Children’s Hospital, and my
colleagues and I were astonished at how little functional lung
remained (less than 20 percent) and the fact that the child
played actively and had an oxygen saturation of over 90 percent
on room air. Since her liver was still enlarged, she was treated
with another course of 2-CdA alone at a reduced dose while
awaiting the decision about a lung transplant. One month after
that therapy, a CT of her lungs showed an amazing amount of good
lung tissue – more than 40 percent. This could have resulted
from resolution of nodules causing blockage of bronchi and cysts
such that functional lung became aerated again. It also is
possible that this young child could have redeveloped functional
lung tissue. Given the good response, it was decided to give the
child some more time to grow and decide later if a lung
transplant is needed.
Texas Children’s Cancer Center’s Histiocytosis Center has been
participating in the Histiocyte Society trials for more than 10
years and is a leading contributor of patients to these trials,
as well as a referral center for patients from all over South
and North America seeking help with the diagnosis and treatment
of the histiocytic disorders including LCH, Hemophagocytic
Lymphohistiocytosis (HLH), Rosai-Dorfman disease (Sinus
Histiocytosis with Massive Lymphadenopathy), juvenile
xanthogranuloma, Erdheim-Chester Disease and others.
It is only through cooperative trials that progress will be made
in understanding the cause and cure of these rare diseases. We
welcome your questions and look forward to collaborating with
you.
Kenneth McClain, M.D., Ph.D., is the clinical director of
Texas
Children’s Cancer Center’s Histiocytosis Center and professor of
pediatrics of Baylor College of Medicine.
Dr. McClain and his staff see more than 40 new patients annually
in Texas Children’s Cancer Center’s Histiocytosis Center. A
leader in promoting trials of new drugs – such as thalidomide
for low-risk LCH and use of vincristine and cytosine arabinoside
for central nervous system LCH – the goal of the center is to
provide the latest therapeutic options for patients while
supporting the efforts of physicians worldwide in placing
patients in the Histiocyte Society’s clinical trials.
McClain KL, Drug Therapy for
Treatment of Langerhans Cell Histiocytosis. Expert Opinion on
Pharmacotherapy.2005;6:2435-2441. PMID: 16259575
Braier J, Latella An, Balancini
B, et al. Outcome in Children with Pulmonary Langerhans Cell
Histiocytosis. Pediatr Blood Cancer 2004;43:765-769. PMID:
15390304
Grois N, Potschger U, Prosch H,
et al. Risk factors for diabetes insipidus in langerhans cell
histiocytosis. Pediatr Blood Cancer. 2006 Feb;46(2):228-33.
PMID: 16047354
Weitzman S, McClain KL, Arceci
R. Salvage Therapies for Langerhans Cell Histiocytosis. In:
Egeler RM and Weitzman S. Editors Histiocytic Disorders of
Children and Adults. Cambridge Press, Cambridge. 2005,
pp254-271.
McClain KL, Kozinetz C. A phase
II trial using thalidomide for Langerhans cell histiocytosis.
Pediatr Blood Cancer. 2005 Dec 6; [Epub ahead of print]
PMID: 16333818 |
