ATRA Based (Iraqi) Protocol for Children with Acute Promyelocytic Leukemia (APL) in Baghdad: Results in the First 8 Patients.

At the Oncology Unit/Al Mansour Teaching Hospital for Pediatrics in Baghdad, Iraq, between January 2002 and January 2003, a total of 11 children (age < 15 years) out of 32 acute myelogenous leukaemia (AML), were morphologically diagnosed as APL. This represents an overall very high incidence (35%) of childhood AML referred to a single institution. Molecular and cytogenetic studies were not feasible. ATRA was not available and most children received combination cytarabine and daunorubicin induction treatment that resulted in more than 50% early fatalities mainly due to hemorrhagic events and in less than 10% survivors. As a consequence of a collaborative project between the Oncology Unit/Al Mansour Teaching Hospital for Pediatrics in Baghdad and the Pediatric Hematology Unit of our Institute at “La Sapienza” University of Rome, a specific ATRA based protocol was designed according to the modern strategies for the management of APL and adapted to the severe local difficulties in Iraq. ATRA was supplied by Roche. The treatment plan consisted of oral induction ATRA (25 mg/m²/day) for 30 days associated to Daunorubicin (DNR 25 mg/m²/day for 2 consecutive days) only if the WBC count was > 10 x 10⁹/L at diagnosis or increased during treatment. Consolidation included three chemotherapy cycles (DNR; DNR+ARA-C; DNR); ATRA was associated to each cycle for patients with a WBC count at diagnosis > 10 x 10⁹/L and/or for those requiring the addition of DNR during ATRA therapy (high-risk). Standard 6-MP and MTX maintenance with 14 days ATRA, every 3 months was administered to all patients in complete remission (CR) for 2 years. Intrathecal MTX prophylaxis (total 3 doses) was given at each consolidation course, for high-risk patients.

Since December 2003, 8 consecutive children with APL (5 male and 3 female; median age: 12 years, range 3–16) were enrolled in the protocol. Seven were defined as high-risk and one as low-risk. Morphological diagnosis was that of classic M3 in 7 children and of M3 variant in 1. The M3v child had a very high WBC count and died the same day of referral due to a massive bleeding, while the other 7 children achieved a CR. One of the 7 responders was lost to follow-up in CR; the other 6 patients are alive and well in CR, on consolidation (1 case) and on maintenance treatment (5 cases).

These preliminary but highly encouraging results represent a substantial improvement over the earlier experience in childhood APL in the main Pediatric Center in Baghdad and demonstrate that modern therapeutic strategies, adapted to the local reality, are a necessity and can be effectively implemented through international collaborative efforts even in countries with limited resources and severe difficulties.