Cytoprotective Effect of Palifermin on Gastrointestinal Mucous Membrane Enabled Non-Myeloablative Chemotherapy Administration in ALL Patient with High Risk of Gastrointestinal Toxicity.

Palifermin (Keratinocyte Growth Factor, KGF) is indicated to decrease the incidence, persistence and severity of mucositis in patients with hematologic malignancies receiving myeloablative chemotherapy with consecutive hematopoietic stem cell support. Hereby we present a clinical case of acute lymphoblastic leukemia (ALL) patient with a high risk of gastrointestinal complications who received intensive reinduction and consolidation chemotherapy together with KGF. 21-years old male with common ALL (BCR/ABL negative) with primary central nervous system (CSN) infiltration diagnosed in 2003, received two doses of standard induction therapy (vincristine + epirubicin) and four doses of intrathecal methotrexate (4 x 20mg) and arabinoside cytosine (4 x 50mg) with consecutive development of severe intestinal mucositis resulted in ileus perforation. After repeated procedure of laparotomy surgery the extended right hemicolectomy must had been performed. The patient remained in complete remission (CR) and was disqualified for following chemotherapy. After 23 months the patient relapsed with 90% of bone marrow infiltration and right testis involvement. Local irradiation was performed. Because of a high risk of severe life-threatening intestinal mucositis KGF was administered together with the second induction therapy according to PALG4-2002 protocol (Polish Adult Leukemia Group www.palg.pl). Patient’s informed consent and local Ethics Committee approval were obtained. KGF was administered 60μg/kg during three consecutive days before each cytostatics infusion with retaining of 24–48 hrs period between KGF and chemotherapy dose. No gastrointestinal side effects were observed, thus consolidation chemotherapy with non-reduced doses was performed. The only side effects that occurred during the treatment were taste alteration and subjective sensation of gustatory buds hypertrophy. A generalized intense bone pain during concomitant administration of KGF and granulocyte-colony stimulating factor (G-CSF) was observed. This seems to be significant because the symptom did not appear when the two drugs were administered separately. Currently the patient remains in CR and is qualified as eligible for allogeneic stem cell transplantation (SCT). A cytoprotective activity of KGF on distal parts of gastrointestinal tract has been concluded based on the case of intensive chemotherapy administered together with KGF in patient with high risk of severe chemotherapy-related intestinal mucositis. That may allow significantly reduce incidence and severity of gastrointestinal mucositis not only in patients receiving myeloablative chemotherapy but also in those who developed chemotherapy-related severe mucositis after non-myeloablative treatment. The excellent chemotherapy tolerability without any serious complication and no gastrointestinal side effects allows taking into consideration KGF administration in patients with hematological malignancies and high risk of severe mucositis.