Search

In the 2016 revision of the World Health Organization classification the term therapy-related myeloid neoplasia (t-MN) defines a subgroup of acute myeloid leukemia (AML) comprising patients who develop myelodysplastic syndrome (MDS-t) or acute myeloid leukemia (AML-t) after treatment with cytotoxic and/or radiation therapy for various malignancies or autoimmune disorders. We report the case of a 36 year old patient with t-MN (t-MDS) after achieving complete remission (CR) of a PML-RARA positive acute promyelocytic leukemia (APL) at 32 months after diagnosis. Initially classified as low risk APL and treated according to the AIDA protocol - induction and 3 consolidation cycles - the patient achieved a complete molecular response in September 2013 and started maintenance therapy. On follow-up PML-RARA transcript remained negative. In January 2016 leukopenia and thrombocytopenia developed and a peripheral blood smear revealed hypogranular and agranular neutrophils. Immunophenotyping in the bone marrow aspirate identified undifferentiated blast cells that did not express cytoplasmic myeloperoxidase. The cytogenetic study showed normal karyotype. The molecular biology tests not identified PMLRARA transcript. A diagnosis of t-MDS (AREB-2 - WHO 2008) was established. Treatment of AML was started with 2 “3+7” regimens and 1 MEC cycle. Two months from diagnosis, while in CR, an allogeneic HSCT from an unrelated HLA compatible donor was performed after myeloablative regimen. An unfavorable clinical evolution was followed by death on day 9 after transplantation. The occurrence of t-MNs during CR of APL represents a particular problem in terms of follow-up and differential diagnosis of relapse and constitutes a dramatic complication for a disease with a favorable prognosis.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder that is characterized by the presence of an absolute monocytosis (1 × 10^ 9/l) in the peripheral blood, the overlap of myelodisplastic aspects and myeloproliferative aspects in the bone marrow and tendency to transform into acute myeloid leukemia. CMML is considered to be the most aggressive chronic myeloid leukemia. We present the case of a 48 years old woman who was hospitalized in March 2013 in the Center of Hematology and Bone Marrow Transplantation for anemia related symptoms. Initial investigations showed anemia, relative monocytosis (10% monocytes of the WBC differential) with an increasing absolute number of monocytes (> 1,000/μl) in the following months. Initial exploration of the bone marrow (aspirate and bone marrow biopsy and immunohistochemistry IHC tests) revealed elements of trilinear dysplasia and an increased percentage of myeloblasts (11-14%). In the next four months myeloblasts percentage remained below 20% (8-14%) and it has been observed a gradually increasing of monocytoid elements (> 20%). Immunophenotyping in the bone marrow aspirate identified a monocytic proliferation with high percentage (8%) of immature cells. The karyotype reported the presence of clones with t (1;3). Initially diagnosed as RAEB-2 (WHO) the case was recomitted in CMML-type 2 with a progression to acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been performed after getting the best possible therapeutic response with AML chemotherapy type (complete remission). Allo-HSCT was performed using myeloablative conditioning, 12 months after diagnosis. The patient is now in complete remission, 24 months after allo-HSCT.

Scopul acestui studiu, parte a proiectului PERSOTHER, este implementarea unei tehnici noi - hibridizarea in situ cu imunofluorescenţa (FISH) - in diagnosticul limfoamelor Burkitt (BL), pentru prima dată în ţara noastră. BL este un limfom cu celulă B de mare agresivitate clinică. Sunt recunoscute 3 variante de LB: endemică (în Africa ecuatorială), sporadică (peste tot in lume) şi asociată cu imunodeficienţa. Clasificarea Organizaţiei Mondiale a Sănătăţii din 2008 a descris o nouă formă de limfom cu celulă B, neclasificabil, cu caractere intermediare între un limfom difuz cu celulă mare B şi un BL. Deoarece tratamentul BL este foarte agresiv, cu chimioterapie in doze mari, un diagnostic corect este obligatoriu. Citologia, morfologia şi imunofenotipul (CD20+, CD10+, BCL6+, BCL2-, Ki67 98-100%) sunt tipice pentru BL. Majoritatea au o translocaţie a genei MYC, localizate pe 8q24 cu gena pentru IgH, 14q32. Demonstrarea transocaţiei MYC este necesară pentru diagnosticul de BL şi pentru diferenţierea de un DLBCL, în unele cazuri. 22 de cazuri de BL au fost evaluate prin FISH pentru translocaţia MYC. 17 cazuri au fost pozitive, un caz a fost negativ şi 4 cazuri au fost neconcludente. Aceste rezultate sunt concordante cu literatura de specialitate: autorii raportează aproximativ 10% cazuri de BL fără transocaţie MYC. În aceste cazuri pot fi implicate alterări ale micro-ARN. Studiul actual evidenţiază importanţa FISH in diagnosticul BL, identifică unele dificultăţi tehnice ale metodei şi reprezintă pentru viitor, o bază a diagnosticului de rutină, în cazuri selecţionate.