Unrelated bone marrow transplant for congenital amegakaryocytic thrombocytopenia: Report of two cases and review of the literature

Abstract

CAMT is a very rare cause of thrombocytopenia in infants. Most of the patients will progress to marrow failure. Allogeneic stem cell transplant remains the only curative therapy. We present two patients with CAMT who underwent an unrelated donor bone marrow transplant, one after developing marrow failure and another early in the course of the disease. Both patients tolerated the transplant with minimal toxicity and durable engraftment. We also present a comprehensive review of the literature for unrelated donor transplant for this condition.

Congenital Amegakaryocytic Thrombocytopenia: Clinical Presentation, Diagnosis, and Treatment

“…Nevertheless, there are reports on CAMT patients with inconspicuous BM findings or only slightly reduced numbers of megakaryocytes at the time of an initial BM analysis, although ineffective megakaryopoiesis was confirmed as the cause of the thrombocytopenia at later marrow examinations. 10,36,37 Most of the CAMT patients show a progression toward a hypocellular BM during the course of the disease. This exhaustion of hematopoiesis reflects the important and nonredundant role of THPO for the regulation of hematopoietic stem cells, a topic that has been previously reviewed.…”

“…1). 2,3,15,16,19,[24][25][26][27][28]31,32,[35][36][37][38][39][40][41] Although mutations have been reported for all coding exons of the MPL gene, there is a significant excess of mutations located in the first five exons that encode the first cytokine receptor homology domain. Three-quarters of all mutations which have been detected in CAMT patients are in this region, and over 60% of mutations are in exons 2 and 3 alone.…”

“…Allogeneic HSCT is the only curative treatment option for CAMT patients progressing to pancytopenia and the only curative therapy reported so far (see below). A total of 52 CAMT patients treated with HSCT have been reported, [10][11][12][13][14][15][18][19][20][21][22][23][24][25][26][27][36][37][38] and among this group, 26 had a confirmed MPL mutation.…”

What To Do When You Suspect an Inherited Platelet Disorder

“…62 BM transplantation has been performed in a patients with WAS and GT, resulting in normalization of platelet function and megakaryopoiesis. 63,64 There have been similar efforts in GT, but it most such patients have a near-normal lifestyle and the cost-benefit of such therapy needs better evaluation. Use of autologous platelet-rich clots has also been reported to be effective in skin biopsy and dental extraction in patients with type 2 VWD, platelet-type VWD, and GT.…”

T-cell-depleted hematopoietic SCT from unrelated donors for the treatment of congenital amegakaryocytic thrombocytopenia

“…2 A total of 11 patients with CAMT who received transplants from unrelated donors have been described in the literature (Table 2). [1][2][3][4][5][6][7][8] Nine patients received unmodified grafts from matched-unrelated donors, and two patients received one allele mismatched-unrelated cord-blood transplants. Three of the 11 patients failed to engraft: One patient following an unmodified BMT from a matched-unrelated donor after cytoreduction with TBI/ CY, one patient following an unmodified BMT from a matched-unrelated donor after cytoreduction with BU/CY/ATG and one patient following a single HLA allele mismatched-unrelated cord-blood transplant after cytoreduction with TBI/CY/methylprednisolone/ATG.…”