Extramedullary (EM) relapses of acute leukemia (AL) without concomitant bone marrow involvement are increasingly reported as a late complication after allogeneic hematopoietic stem cell transplantation (alloHSCT), however, the data regarding their incidence in larger cohorts of patients (pts), treatment options and long-term outcome are scarce. We retrospectively analysed this mode of leukemia recurrence in a group of 324 consecutive pts with AL (123 with ALL, 201 with AML, F/M 156/168, median age 29 years, range 10–61) who underwent alloHSCT in our institution between June 1993 and December 2007. 62 pts (34 with ALL, 28 with AML) relapsed (any site) after a median time of 8 months (range, 1–77 ). 7 (11,3 %) out of all pts who relapsed (2 with pre-pre B ALL, 2 with CD10+, Ph+ ALL, 2 with 45 X, −Y, t(8;21) AML, 1 with CD117+, 46, XY, t(19;11), del 13 AML, F/M 4/3, median age 29 years, range 28–40 years) developed isolated EM infiltrates after a median time of 13 months (range, 8–33 months) after alloHSCT. The leukemic origin of pathologic infiltrates was confirmed in each case by immunohistochemical methods or flow cytometry with the use of appropriate combination of the following markers: CD10, CD19, CD20, CD45, CD79a, CD34, TdT, CD13, CD33, CD117, MPO, lysozyme. We revealed complete donor chimerism in 6/7studied pts. 4 pts (3 with ALL, 1 with AML) developed skin and/or subcutaneous tissue infiltrates; in one of them ( patient with pre-preB ALL) leukemic tumor of the peritibial soft tissues was additionally observed. Other sites of EM relapse included (No. of cases/diagnosis): leptomeninges of the brain (1/Ph+ ALL), paraspinal soft tissues (1/AML), small intestine and the root of mesentery (1/AML). Treatment plans for those isolated EM relapses included (No. of cases/diagnosis): 1/involved-field radiotherapy (IF-RT) followed by chemotherapy (CHT) and interpheron-alpha (2/pre-pre B ALL), 2/imatinib + CHT + steroids and methotrexate intrathecally (1/Ph+ ALL), 3/imatinib + CHT (1/Ph+ ALL), 4/CHT (1/AML), 5/dasatinib (1/CD117+ AML,), 6/surgery (1/AML). In one patient who showed peritibial infiltrates, donor lymphocyte infusions and daunorubicine injections to the femoral artery, as well as total skin electron irradiation due to recurrent skin involvement were additionally applied. Unfortunately, all of the patients died after a median time of 10 months (range, 1–30) due to resistant systemic relapse and/or infectious complications. Only one patient who responded well to IF-RT was alive more than 2 years following relapse. Our data indicate that the graft-versus-leukemia effect observed in the EM sites of the body may not be as effective as in the bone marrow in some pts with AL following alloHSCT. Isolated EM disease affects slightly more often ALL than AML pts relapsing after alloHSCT. Sites of EM relapses vary widely among the pts with skin and/or subcutaneous tissue being frequently involved. Local radiation therapy seems to be effective treatment option, but it does not prevent from systemic relapse and should be followed by other therapeutic modalities. In selected pts with specific indications individualized management, such as intraarterially administered anthracyclines or total skin electron irradiation may result in transient improvement. Tyrosine kinase inhibitors such as imatinib or dasatinib should also be considered in cases of Ph+ ALL or c-kit positive AML. According to our experience occurrence of EM relapse following alloHSCT is associated with poor prognosis and the optimal therapy remains a challenge.
Disclosures: No relevant conflicts of interest to declare.