Acute Lymphoblastic Leukemic Transformation in a Patient With Chronic Idiopathic Myelofibrosis and Paroxysmal Nocturnal Hemoglobinuria: A Case Report and Review of the Literature

Abstract

Leukemic transformation of chronic idiopathic myelofibrosis (CIMF) to acute lymphoblastic leukemia (ALL) is rare. We report a case of a patient with CIMF who developed paroxysmal nocturnal hemoglobinuria (PNH) 2 years after initial presentation. His disease eventually transformed to ALL of precursor B-cell type. In that CIMF and PNH are clonal stem cell disorders with different pathogeneses, there may be an association between them. However, leukemic transformation is a rare sequel of both disorders. Coexistence of CIMF and PNH and subsequent transformation to ALL have, to our knowledge, never been previously reported in the world literature. The simultaneous presentation of CIMF and PNH, complicated by the rare sequela of leukemic transformation, raises important issues with regard to diagnosis and treatment.

Clinical and prognostic significance of small paroxysmal nocturnal hemoglobinuria clones in myelodysplastic syndrome and aplastic anemia

“…Although none of them developed classic hemolytic PNH, we demonstrated the persistency of PNH clones in 88% of the 26 cases that had been tested at least twice. Some Authors described the occurrence of PNH clones in MPN [ 13 – 15 ], and Fraiman et al reported one patient developing a PNH clone of 60% on granulocytes and hypothesized the cooperation with CALR driver mutation in PNH clone selection and expansion [ 14 ]. Similar data were recently confirmed by Richards et al in five patients with MPN that mainly showed association of PIG-A mutation and JAK2 V617F or other MPN driver mutations [ 13 ].…”

Coexistence of Primary Myelofibrosis and Paroxysmal Nocturnal Hemoglobinuria Clone with JAK2 V617F, U2AF1 and SETBP1 Mutations: A Case Report and Brief Review of Literature

“…In PNH, acquiring additional MPN-associated gene mutations might promote clonal expansion of the PIGA mutant clone, consequently inducing clinical manifestation of both MPN and PNH [27]. Interestingly, a few cases of coexistence of PMF and PNH have been reported (Table 2) [11,12,14,16]. One recent study reported that PNH clones were found in 2% of MPN patients [15].…”

“…Interestingly, a few cases of coexistence of PMF and PNH have been reported ( Table 2 ) [ 11 , 12 , 14 , 16 ]. One recent study reported that PNH clones were found in 2% of MPN patients [ 15 ].…”

“…According to the previous reports, some patients were initially diagnosed with MPN and PNH together, harboring concomitant MPN associated genes and PIGA gene mutations [ 14 , 16 , 17 , 27 ]. Another report showed that patients were initially diagnosed with MPN, following eventual evolution of PNH [ 11 , 12 , 13 ], while other patient was diagnosed as PNH at first and then developed MPN later [ 12 ]. Taken together, MPN and PNH association may be attributed to the PNH clone arising either from the MPN-mutated populations or in parallel with the MPN mutated populations and vice versa.…”

“…There have been a few reports of the concomitant MPN and PNH [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ], whereas a close association between PNH and aplastic anemia (AA)/myelodysplastic syndrome (MDS) has been well known [ 18 ].…”