Incidence, Clinical Presentations and Management of Isolated Extramedullary Relapses After Allogeneic Hematopoietic Stem Cell Transplantation for Acute and Chronic Leukemias: An Updated Single-Center Analysis of 612 Patients.
Authors: Kata Dariusz , Markiewicz Miroslaw , Czerw Tomasz , Seweryn Marek , Kyrcz-Krzemien Slawomira 
Published: October 2019

Abstract
Abstract 4506

INTRODUCTION.
Isolated extramedullary relapses (IER) are increasingly reported as long-term complications after allogeneic hematopoietic stem cell transplantation (alloHSCT) for leukemias. However, the optimal treatment strategies for IER following alloHSCT have not been established.

AIMS AND METHODS.
We retrospectively analysed incidence, clinical features, treatment options and long-term outcome of this mode of leukemia recurrence in a cohort of 612 consecutive patients (pts) (147 with ALL, 237 with AML, 213 with CML, 15 with CLL) who underwent alloHSCT in our institution between June 1993 and December 2008. 87 pts (35 with ALL, 31 with AML, 18 with CML, 3 with CLL) relapsed (any site).

RESULTS.
10 (11%) out of all pts who relapsed (5 with B-line ALL, 4 with AML, 1 with CML, F/M 5/5, median age 29,5 years, range 28 – 46 years) developed IER after a median time of 18,5 months (mts) (range, 8 – 80 mts) following alloHSCT. We revealed complete donor chimerism in 8/10 studied pts. 4 pts (3 with ALL, 1 with AML) developed skin and/or subcutaneous tissue infiltrates; in one of them (patient with ALL) leukemic tumor of the peritibial soft tissues was additionally observed. Other sites of IER 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), inguinal lymph nodes (1/AML), paranasal sinuses (1/AML), multiple bones (1/ALL) Treatment plans for those IER included (No. of cases/diagnosis): 1/involved-field radiotherapy (IF-RT) followed by chemotherapy (CHT) and interferon-alpha (2/ALL), 2/imatinib + CHT + steroids and methotrexate intrathecally (1/ALL), 3/imatinib + CHT (1/ALL), 4/CHT (2/AML, 1/ALL), 5/dasatinib (1/CD117+ AML,), 6/surgery (1/AML), 7/surgery + IF-RT (1/CML). 7/10 pts died after a median time of 10 mts (range, 1 – 30) due to resistant systemic relapse and/or infectious complications, 3/10 pts are currently under CHT.

CONCLUSIONS.
Our data indicate that IER following alloHSCT occur predominantly in acute leukemia pts, being rarely observed in pts with CML. No cases of IER have been reported among CLL pts. Sites of IER 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. Our observations suggest also that insufficient graft versus leukemia mechanism may result in unusual clinical appearance of disease progression, temporarily restricted to focal infiltrates that precede leukemic generalization. Due to the lack of efficacious treatment strategies, there is a need for novel approaches to manage IER after stem cell transplantation.

Disclosures:
No relevant conflicts of interest to declare.