Bone Marrow Failure: Congenital Amegakaryocytic Thrombocytopenia- A Case Report of Successful Matched Unrelated Bone Marrow Transplantation in Pediatric Twins

Congenital Amegakaryocytic Thrombocytopenia (CAMT) is a rare inherited autosomal recessive bone marrow failure disorder that presents with thrombocytopenia and absence of megakaryocytes.   Bleeding/bruising is typically recognized on day 1 of life or at least within the first month, with risk of life threatening hemorrhage, requiring platelet transfusions and progression to bone marrow failure and leukemic transformation later in life.  Diagnosis is confirmed by the MPLgene testing.  Allogeneic stem cell transplantation remains the only curative therapy.  Due to its rarity, there are few published reports with variable conditioning regimens in the allogeneic setting. 

We report two female identical twin siblings with thrombocytopenia at birth (11,000 and 9,000 respectively) and subsequent work up for persistent low platelets revealed heterozygous R102P missense mutation on exon 3 of MPL gene. No phenotypic abnormalities noted and Fanconi anemia testing was negative.  One of them progressed to aplastic anemia (bone marrow cellularity< 30%, no clonal abnormality) and received conditioning with Cytoxan 50mg/kg x 4 days, reduced dose of TBI at 200cGY x 1 and Campath 3mg/kg x 4 days followed by transplant with 10/10 allele matched, unrelated, CMV + donor bone marrow. Tacrolimus alone was used for GVHD prophylaxis. Sister received myeloablative conditioning using once a day Busulfan for 4 days based on pharmacokinetics, Cytoxan 50mg/kg x 4 days, Campath 5mg/kg x 3 days followed by a transplant with the same unrelated bone marrow donor.  Tacrolimus and mini methotrexate were given on days +1, +3, +6, + 11.  Both sisters tolerated the transplant with minimal toxicity, durable engraftment, and no acute or chronic GVHD.  The first twin is approximately 1.5 years post BMT and the second is past day 100.

For matched unrelated donor transplant, the conditioning regimen used may be variable based on patients’ clinical presentation, bone marrow cellularity and presence of comorbidities.