a-ß T/CD19-Depleted Haploidentical Hematopoietic Stem Cell Transplant (HSCT) as a Rescue Strategy in Blast-Phase Chronic Myeloid Leukemia Relapsing after a Matched Unrelated HSCT with Extramedullary Involvement: A Case Report

Special Article - Acute and Chronic Myeloid Leukemia

Ann Hematol Oncol. 2016; 3(11): 1124.

a-ß T/CD19-Depleted Haploidentical Hematopoietic Stem Cell Transplant (HSCT) as a Rescue Strategy in Blast-Phase Chronic Myeloid Leukemia Relapsing after a Matched Unrelated HSCT with Extramedullary Involvement: A Case Report

Cambò B1, Crugnola M1, Prezioso L1, Sammarelli G1, Bonomini S1, Craviotto L1, Mancini C2, Martella EM2, Masselli E1*, Bonifazi F3, Arpinati M3 and Aversa F1

1Department of Clinical and Experimental Medicine, Parma University Hospital, Italy

2Department of Diagnostics, Parma University Hospital, Italy

3Bone Marrow Transplant Unit, Bologna University Hospital, Italy

*Corresponding author: Elena Masselli, Hematology and BMT Unit, Department of Clinical and Experimental Medicine, Parma University Hospital, Via Gramsci n. 14, 43126 Parma, Italy

Received: November 02, 2016; Accepted: December 02, 2016; Published: December 05, 2016

Perspective

Blast crisis (BC) and extramedullary involvement (EI) are rare and aggressive clinical manifestations of chronic myelogenous leukemia (CML) that challenge the patient treatment algorithms also in the TKI-era. An adequate therapeutic approach for these patients need to consider the intrinsic biology of this disease, which is one of the most immunogenic hematologic neoplasm. Here we present an emblematic case of a patient with BC-CML, initially treated by allogenic bone marrow transplant from HLA-matched unrelated donor, who relapsed with EI under TKI maintenance. Only a-ß T cell depleted haploidentical stem cell transplant allowed to achieve stable disease remission, leading us to speculate that preserving the immunologic properties of the graft and avoiding immunosuppressive therapy is of utmost relevance in the transplantation strategy of CML.

Keywords: Chronic myelogenous leukemia; Blast crisis; Extramedullary involvement; Tyrosine kinase inhibitors; Hematopoietic stem cell transplant; TCR a-ßT-cell depletion

Introduction

Blast crisis (BC) and extramedullary involvement (EI) are both rare, aggressive clinical manifestations of chronic myelogenous leukemia (CML), that confer a dismal prognosis and challenge the conventional therapeutic approach to this disease. While EI by CML occur sporadically [1-4], up to 6.7% patients are in BC at the time of diagnosis.

Although the introduction of tyrosine kinase inhibitors (TKI) had a profound impact in altering the natural history of CML, reducing the disease progression rate from >20% to 1-1.5% per year, their effectiveness in uncommon presentations such as EI and BC is still controversial. In this setting, a therapeutic algorithm that considers allogenic hematopoietic stem cell transplantation (HSCT) configures as the only curative chance for these patients also in the TKI-era [5]. Here we present a case in which a a-ßT cell/CD19-depleted haploidentical HSCT successfully rescued a patient with BC-CML who had relapsed with EI after allogeneic transplant from a HLAmatched unrelated donor.

Case Presentation

In November 2009, a 42 year-old man was referred to our institution for leucocytosis (WBC= 28x109/L), moderate anemia (Hb =10.2 g/dl) and mild splenomegaly. The patient complained constitutional symptoms and presented a relevant history of previous exposure to chemotherapeutic agents for testicular lymphoma.

A diagnosis of blastic transformation of a chronic myeloproliferative disease was done on the basis of the peripheral blood morphology (Figure 1A), bone marrow aspirate immunophenotype (Figure 1B) and bone marrow biopsy showing increased cellularity with marked granulocytic precursor hyperplasia accompanied by reduced erythro- and megakaryopoiesis and a blast count of 40%. Cytogenetic analysis revealed the Philadelphia chromosome in the 56% of the examined metaphases and one metaphase with the following readout, encompassing all the so called “major route” abnormalities: 57, XY, t(9;22)(q34;q11), +der(22)t(9;22)(q34;q11.2), +6, +7, +8, +9, +10, +14, +19, +21, +21, +21 (Figure 2A and B). FISH analysis confirmed the presence of extra-copies of the Philadelphia chromosome and molecular analysis was positive for BCR-ABL hybrid gene (b3a2 p210).