OK432 (Picibanil) in the Treatment of Lymphatic Malformations

Lymphatic malformations are uncommon tumors that represent localized malformations in the
development of the lymphatic system. They typically present in children under 2 years of age
and in almost 50% of the cases, are diagnosed at birth. There is neither a racial nor a
sexual tendency. The malformations can occur anywhere on the body, but typically they are in
the head/neck area.

Morbidity can be significant. Besides the obvious cosmetic deformity caused by these tumors,
there is risk of infection and airway compromise and even obstruction. However, effective
therapeutic options are limited. Small lesions can be observed, although spontaneous
resolution is unlikely. For larger lesions, surgery has been the traditional form of therapy.
In the head and neck, in particular, lymphangiomas typically wrap themselves around major
neurovascular structures, making total excision removal difficult, if not impossible, and
thus the likelihood of recurrence is quite high.

Because of these surgical limitations, alternate therapies have been considered; including
cryotherapy, diathermy, and chemical sclerotherapy.

The investigators experience with using the drug for macrocystic disease(large cysts) since
1992 in the United States has been very promising compared to traditional surgery. Recurrence
rate to date, has been very minimal as well. (<2%)

Inclusion Criteria:

To be eligible to receive OK432 immunotherapy

- Patients must be ages 6 months to 17 years

- Patients must have a macrocystic Lymphatic Malformation

- Patients may have had surgical treatment for their Lymphatic Malformation

- Patients must have an imaging study to confirm the diagnosis of a macrocystic or mixed
Lymphatic Malformation An MRI is preferred over a CT scan (an ultrasound may be used
between injections if warranted, however an MRI or CT should be done pre and post
treatment)

Exclusion Criteria:

- Penicillin allergy

- Women who are pregnant or nursing

- Patients who present with a temperature of 100.5 degrees F or greater

- Patients with mixed hemangioma-lymphangioma lesions

- Patients with a history OR a family history of rheumatic heart disease or
post-streptococcal glomerulonephritis

- Patients with hemodynamic instability and respiratory failure

- Patients with a history OR a family history of obsessive-compulsive, tic disorders, or
PANDA (pediatric autoimmune neuro-psychiatric disorder associated with streptococcal
infections)

- Patients who demonstrate abnormalities in the history, physical examination or
laboratory analysis which may indicate significant hepatic, hematologic, or renal
disease

- Patients who are not in "good general health" (including patients with congenital
disorders, chronic diseases, immunologic dysfunction, transplant recipients)