High Incidence of Extramedullary Relapses Following Allogeneic Bone Marrow Transplant (Allo-BMT) in Adults with Acute Lymphoblastic Leukemia.

Allo-BMT represents a curative therapy for certain patients with ALL. Unfortunately, leukemia relapse still represents a major problem following allo-BMT. Studying the pattern of relapses following allo-BMT may shed some light into the exact mechanisms of such relapses and suggest better ways to prevent them. Extramedullary relapses have been reported following allo-BMT for ALL. We investigated the pattern of ALL relapses in 57 patients after allo-BMT. All donors were HLA matched serologically at HLA A, B, and DR. All patients were treated with high-dose busulfan (16 mg/kg) combined with cyclophosphamide (120 mg/kg) with or without etoposide (50 mg/kg) and all received GVHD prophylaxis, excluding T-cell depletion. We identified 57 patients with ALL treated with BMT between 1987 and 2001. 45 patients (78.9%) had a matched related donor (MRD) and the rest had matched unrelated donors (MUD). 22 patients (39%) relapsed, 8 patients had an isolated extramedullary (IEM) relapse and 14 patients had bone marrow relapse (BM-R) with or without an isolated extramedullary relapse. The median time to relapse for the IEM relapses was 432 days with a range of 139–1422. This was significantly longer than the median time to relapse with BM (median 192 days and range 40–498) P=0.016. The following table shows the characteristics of both groups:

IEM relapses occurred in different organs including mastoid sinus, mediastinum, pericardium, nasopharyngeal lymphoid tissue, bone, CNS, and breast. Hematopoietic chimerism was determined utilizing the polymerase chain reaction (PCR) amplification of Short Tandem Repeat (STR) loci on DNA extracted from peripheral blood leukocytes compared with Pre-Transplant STR loci of donors and recipients. At the time of relapse all the patients with IEM relapses had 100% donor chimerism. Treatment plans for those IEM relapses included donor lymphocytes infusion (DLI), local radiation therapy, reinduction chemotherapy, imatinib for Ph+ patients, and one patient had an additional Allo-BMT. Only one patient in the IEM relapse group eventually had a relapse in the bone marrow, only 2 patients (25%) were alive more than 2 years following relapse and 3 patients died due to transplant complications.

We concluded from our review that IEM relapse following Allo-BMT for ALL is not an uncommon occurrence. These relapses may have a wide-range of clinical presentations depending on the organ affected which makes the diagnosis of this type of relapse challenging. These relapses have, usually, a late occurrence compared to BM-R, and their pathogenesis is poorly understood. Full donor chimerism does not exclude the possibility of IEM relapse.