Tacrolimus and Short-Term Methotrexate (mini-MTX) for Graft Versus Host Disease (GVHD) Prophylaxis after Unrelated Single Unit Cord Blood Transplant (CBT) in Pediatric Patients.

CBT is increasingly used in the management of patients with a variety of hematologic and neoplastic conditions. We investigated the use of Tacrolimus with MTX for the prevention of GVHD. Sixty consecutive pediatric patients (37 males, median age 6.8 years, range 0.4–20 y) underwent 63 single unit CBT. Sixty-two units were mismatched with the patients (1 Antigen mismatch [Ag MM]: 20; 2 Ag MM: 39; 3 Ag MM: 3). Five patients had non-malignant conditions (severe aplastic anemia [SAA] 2, Wiskott-Aldrich 2, Hunter 1). Thirty-one of the 55 patients with malignant diseases (ALL 30, AML 16, CML 2, NHL 2, MDS 2, JMML 2, neuroblastoma 1) had high-risk disease. The conditioning regimen was chemotherapy-only in 34 (Thiotepa, Busulfan[Bu], Cyclophosphamide[Cy] for 28 children younger than 5 years or with prior irradiation; Bu-Cy in the patient with Hunter and a patient with AML and trisomy 21; Fludarabine[Flu], Cy, Lymphoglobulin in one patient with SAA; Bu-Flu:3) transplants. Radiochemotherapy was implemented in 29 patients (Flu, Melphalan[Mel], TBI: 26; Etoposide, Mel, TBI:1; Etoposide, Mel, TBI:1; Flu, Cy, ATG, 200cGy TBI:1 SAA patient). The median pre-cryopreservation total nucleated cell dose was 4.3 x 10⁷ / kg recipient weight (range 1.8–12 x 10⁷/ kg). The combination of Tacrolimus and mini-MTX (5 mg/m2 on days 1, 3 and 6) was used in 60 transplants (Tacrolimus alone in 3). ATG or steroids were not routinely used.

Results: Forty-six of the 52 transplants evaluable for acute GVHD did not have severe GVHD (Grade 0:11 patients; I: 10 patients; II: 25 with 22 limited to skin only; III: 3; IV: 3 patients). Eight patients had primary graft failure (2 with persistent disease). There were 3 early deaths. Chronic GVHD was diagnosed in 8/42 evaluable patients. With a median follow-up of 1,757 days (range 512–3,731) 27 patients are alive without disease.

Conclusion: Tacrolimus with mini-MTX should be considered for the prevention of GVHD after mismatched unrelated cord blood transplants in pediatric patients with malignant or non-malignant diseases.