Myelodysplatic Syndrom

Myelodysplastic syndrome of 5q- type is generally considered to have a favorable course. But, even in the Lenalidomide era, it has been evidenced that it may be prone to transformation into more advanced disease, especially in patients who fail to reach transfusion independence or complete cytogenetic response or both. In this setting, it has been demonstrated that gain of chromosome 8 and loss of chromosome 7 are among the genetic cooperating events leading to clonal evolution. Treatment choices in such patients are not well codified and outcome is not predictable.

We combined 5′-Azacytidine to Lenalidomide as induction therapy to obtain the best response possible before reduced-intensity conditioning regimen (RIC) allogeneic hematopoietic stem cell transplantation for advanced disease developed from 5q- myelodysplastic syndrome.

A female patient born in 1949 was diagnosed with myelodysplastic syndrome of the 5q- type in 1997. The disease remained stable and the patient free of transfusion requirement until 2004. From 2004 to 2007, due to symptomatic anemia, many treatment lines, based on erythropoiesis-stimulating agents, have been attempted, but without success. Transfusion in red blood cells became necessary once every four weeks in 2006. In 2007, she has been started on Lenalidomide 10 mg daily. A prompt hematologic improvement was observed at two months of treatment, inducing the disappearance of the macrocytic feature and freedom of transfusion requirement. However, cytogenetic control at twelve months on Lenalidomide showed the persistence of the 5q loss. In 2010, at 24 months on Lenalidomide, a recurrence of macrocytic and symptomatic anemia, with red blood cell transfusion dependence, along with neutropenia and thrombocytopenia, was observed. Cytological evaluation of the bone marrow was consistent with transformation into RAEB-1 whereas cytogenetic control showed the occurrence of two 5q- subclones: one expressing trisomy 8, another one displaying monosomy 7. Lenalidomide has been continued on a daily basis, in combination with 5′-Azacytidine which was administered at 75 mg/m²/day as 7-day cycles every 28 days.

Platelet transfusions were necessary during the first two cycles and red blood cell transfusions until the fourth cycle. Neutropenia persisted throughout the treatment duration, with temporary recovery obtained under periodic courses of G-CSF. No infectious complication has been observed. At day 1 of the sixth cycle, bone marrow has been reevaluated. On cytological evaluation, the blast excess has disappeared, dropping from 8% to 1%, nuclei hypolobulation was still present in less than 10% of the megakaryocytic lineage and some dysplastic features were still evident in less than 10% of the erythroblastic and granulopoietic lineages. Conventional cytogenetic evaluation and FISH showed the complete disappearance of the 5q- clone and subclones.

We found that combining Lenalidomide with 5′-Azacytidine may be an effective therapeutic choice in myelodysplastic syndrome of 5q- type previously treated with Lenalidomide alone and transformed into advanced disease. It may allow for inducing cytological and cytogenetic complete response prior to RIC allogeneic hematopoietic stem cell transplantation in eligible patients.

No relevant conflicts of interest to declare.