Isolated Extramedullary Relapses after Allogeneic Hematopoietic Stem Cell Transplantation for Acute Leukaemia: Single-Center Experience with 220 Patients.
Authors: Kata Dariusz , Holowiecki Jerzy , Wojnar Jerzy , Krawczyk-Kulis Malgorzata , Stella-Holowiecka Beata , Krzemien Slawomira , Sadus-Wojciechowska Maria , Helbig Grzegorz 
Published: April 2020

Abstract
Extramedullary (EM) relapses of acute leukaemia (AL) without concomitant bone marrow (BM) involvement are rare after allogeneic hematopoietic stem cell transplantation (alloHSCT) and little is known about their incidence in larger series of patients (pts) and long-term outcome. We retrospectively analysed this mode of leukemia recurrence in a cohort of 220 consecutive pts with AL (88 with ALL, 132 with AML) who underwent alloHSCT in our institution between June 1993 and May 2005. 5 out of 48 pts who relapsed (4 B-line ALL, 1 45 X, -Y, t,(8;21) AML, F/M 4/1, median age 29 years, range 28–38 years) developed isolated EM infiltrates after a median time of 13 months (range, 8–23 months) post alloHSCT. There was no evidence of leukaemic BM involvement at relapse in 5/5 pts. We revealed complete donor chimerism in 4/4 studied pts. The leukaemic origin of pathologic massess 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, MPO. Our data indicate that isolated EM disease following alloBMT affects predominantly high-risk ALL pts. Sites of EM relapses varies widely among the pts, however, in most of them are localised outside the well-defined sanctuaries (i.e. CNS or testis). Local radiation therapy seems to be the most effective treatment option, however, the long-term ouctomes of the pts with EM tumors remain poor. According to our experience in selected pts individualized menagement, such as intraarterially administered anthracyclines or “total skin irradiation” may be of value. Characteristics and clinical course of pts with isolated EM relapse post alloHSCT are summarized in the table below.
The extramedullar relapses after AlloHSCT Patient no Age/sex Disease/subtype, cytogenetics Sites of relapse (post-allHSCT months) Treatment after relapse Survival post relapse (months) Outcome ND = not done, CNS = central nervous system, DLI = donor lymphocyte infusion 1 30/F ALL/CD10+; t(9;22) skin of the head (13) imatinib, chemotherapy 18 Progressive disease with systemic relapse; hypoplastic death following induction 2 29/F ALL/pre-pre B, ND Left distal tibia with soft tissue (23), then soft tissues of the left hand, right forearm, skin at various sites, cervical and axillary lymph nodes (30-52) Radiotherapy (including “total skin irradiation”), IFN-alpha, DLI, daunorubicine injections to the left femoral artery, chemotherapy 30 Systemic relapse; hypoplastic death following palliative chemotherapy 3 28/F ALL/pre-preB; t(4;11) Subcutaneous tissue of the left arm (17) Radiotherapy, oral cytostatics (mercaptopurine, methotrexate), IFN-alpha 17 Systemic relapse, death during induction treatment due to pneumonia 4 28/F ALL/CD10+;t(9;22) CNS, leptomeningeal (8) Chemotherapy (high-dose cytarabine), methotrexate +steroids intrathecally, imatinib 10 Death due to fulminant gastrointestinal infection 5 38/M AML/M2, 45, X,-Y, t(8;21) Small intestine and the root of mesentery (8) Surgery 1 Immediate systemic relapse; death due to infectious complications