For patients with refractory or high risk leukemias, stem cell transplantation is still the only possible curative approach. Those patients, although, without a HLA identical matched sibling, unrelated stem cells are the only stem cell source. In patients with refractory disease this unrelated cells may be unavailable in a short time period. The use of HLA-mismatched familiy donors has been used before, by depleting in vitro T cells or selecting CD34+ cells. These methods are extremely expensive and patients suffer with delayed immune reconstitution. In an attempt to overcome the HLA barrier, Cyclophosphamide, a highly toxic agent against activated T cells, but not myeloablative, has been used after transplantation to ensure engraftment and avoid GVHD. We describe here two patients who were sequentially submitted to a citoreductive protocol described by Schmid et al (Blood 2006) followed after transplantation by Cyclophosphamide (50 mg/kg day +3 and day +4) as described by O’Donnel et al (BBMT 2002). We transplanted 2 boys (16 years-case 1 and 6 years-case 2) with secondary AML after MDS and AML relapse after second SCT respectively. Case 2 received two SCT from his HLA-id brother and was 8 months after the second transplant. Both had active disease at time of transplant and received full bone marrow from there HLA haploidentical mothers (3 loci mismatch). Engraftment was achieved on day +15 in both cases. Chimerism analysis on day +30 showed that they had 96% XX and 95% XX cells respectively in bone marrow. Case 1 never developed GVHD but relapsed after SCT. Case 2 are in complete remission and complete quimera day+90 after SCT. He developed GVHD (skin, liver and gut) were treated with prednisone and Basiliximab and we are now tapering imunossupression.
Herby we demonstrated that haploidentical transplantation with the use of Cyclophosphamide after transplantation can be a useful transplant strategy in high risk patients without a matched sibling donor. Relapse and infections will always be the most frequent complications. In countries with limited health resources a protocol who avoid the expensive costs of cell depletion or selection can be a real alternative for patients without suitable donors.
Disclosure: No relevant conflicts of interest to declare.