Pre-B-cell acute lymphoblastic leukemia with bulk extramedullary disease and chromosome 22 (EWSR1) rearrangement masquerading as Ewing sarcoma

We report a 2-year-old female with a subcutaneous tumor who was initially misdiagnosed as suffering from Ewing sarcoma with a positive EWSR1 rearrangement and EWS/FLI1 transcript. After finding lymphoblasts in peripheral blood, the diagnosis of acute lymphoblastic leukemia was established. This necessitated further analysis of the subcutaneous tumor. The tissue was positive for immature B-cell markers and an immunoglobulin heavy chain gene rearrangement, which confirmed the final diagnosis of common type acute lymphoblastic leukemia with bulk extramedullary disease. The patient was treated with chemotherapy and was in remission 30 months after the diagnosis

Kompleksna varijantna translokacija Philadelphia kromosoma koja uključuje kromosome 1, 9, 12 i 22 u slučaju kronične mijeloične leukemije (KML)

Aim: Chronic myeloid leukemia (CML) is characterized by the Philadelphia (Ph) chromosome created by the reciprocal translocation t(9;22)(q34;q11), resulting in the hybrid gene breakpoint cluster region - Abelson (BCR-ABL1). Around 5–10% of CML cases develop complex variant Ph translocations involving one or more chromosomal regions besides 9 and 22. We report in this study a case of acute lymphoblastic leukemia (ALL) developed from CML displaying a novel four-way translocation. Case report: Complete blood analysis of 46-year-old male patient showed an increase in white blood cells, lower levels of red blood cells and platelets. Bone-marrow sample was subjected to conventional cytogenetic (Giemsa-banding) and fluorescence in situ hybridization methods and four - way translocation was identified. Considering hepatosplenomegaly and breakpoint cluster region that was characterized as major (M-bcr) on quantitative real-time polymerase chain reaction (RQ-PCR), ALL was diagnosed as a transformation from CML. Conclusion: This study reports new four-way translocation ins(22;1)(q11.2;q31q32)t(1;9;12;22)(q32;q34;q13;q11.2) in an ALL patient developed from the CML and was cross-checked in Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer.Cilj: Kronična mijeloična leukemija (KML) karakterizirana je Philadelphia kromosomom (Ph), koji nastane recipročnom translokacijom t(9;22)(q34;q11.2), i rezultira fuzijskim genom BCR-ABL1. Kompleksna varijantna translokacija uključuje jos jedan ili više kromosoma uz kromosome 9 i 22, te se javlja u 5-10% svih slučajeva KML. U ovoj studiji prijavljujemo novi slučaj varijantne akutne limfoblastične leukemije (ALL) koja se transformirala iz KML. Prikaz slučaja: Kompletna krvna slika 46-godišnjeg pacijenta pokazala je povećane vrijednosti bijelih krvnih stanica, a snižene vrijednosti crvenih krvih stanica i trombocita. Uzorak koštane srži (KS) poslan je na klasičnu citogenetičku (Giemsa-pruganje) i fluorescentu in situ hibridizacijsku (FISH) analizu kojima je potvrđena nova varijantna translokacija između četiri kromosoma. Obzirom na hepatosplenomegaliju i područje prijelomne točke koja je karakterizirana kao „major“ (M-bcr) korištenjem kvantitativne polimerazne lančane reakcije u stvarnom vremenu, dijagnosticirana je ALL u transformaciji iz KML. Zaključak: Ova studija prijavljuje novu varijantnu translokaciju koja obuhvaća 4 kromosoma ins(22;1)(q11.2;q31q32)t(1;9;12;22)(q32;q34;q13;q11.2) kod pacijenta sa ALL transformiranom iz KML, na temelju provjere u bazama podataka „Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer“

Coexistence of trisomy 12 and del(13)(q14.3) in two patients with chronic lymphocytic leukemia

We describe two patients with diagnosis of chronic lymphocytic leukemia (CLL) in whom interphase fluo­rescence in situ hybridization (FISH) analysis revealed trisomy 12 and del(13)(q14.3) occurring in the same clone. These abnormalities are rarely seen together and the prognostic relevance of their coexistence is still unclear. According to some data, a probable adverse prognosis for this group of patients is suggested. Our patients have been in a stable phase of the disease for more than one year since the given abnormalities were documented in their karyotypes. Further study is necessary to determine the prognostic significance of coexistence of these abnormalities in CLL patients

Prognostic factors in myelodysplastic syndromes: single-center experience

Uvod: Mijelodisplastični sindrom (MDS) jedna je od najčešćih klonskih hematoloških neoplastičnih neoplazma starije dobi karakterizirana jednom ili s više citopenija te ograničenim terapijskim rješenjima. Cilj je ovog rada bila retrospektivna analiza klasičnih prognostičkih čimbenika kod bolesnika dijagnosticiranih u jednom centru. Kao glavni ishod uzeto je ukupno preživljenje (engl. Overall survival – OS) definirano kao smrt od posljedica same bolesti ili nekoga drugog uzroka. Metode: Retrospektivno smo analizirali povijesti bolesti svih bolesnika dijagnosticiranih u jednom centru u razdoblju od 1. siječnja 2013. do 31. prosinca 2016. godine. Rezultati: U istraživanje je uključeno ukupno 58 bolesnika s medijanom dobi od 69 godina. Nakon medijana praćenja od 12 mjeseci medijan OS-a iznosio je 17 mjeseci s procijenjenom trogodišnjom stopom OS-a od 25%. U analizi prognostičkih čimbenika zbrojevi rizične stratifikacije prema IPSS-u, R-IPSS-u i WPSS-u bili su statistički značajni te su jasno diskriminirali OS ispitanika s nižim rizikom u odnosu prema OS-u ispitanika s visokom rizikom, no zbog malenog broja bolesnika nije bilo moguće odgovoriti na pitanje koji je bodovni sustav najprikladniji u ovoj populaciji. Citogenetičke kategorije prema IPSS-u i R-IPSS-u bile su statistički značajni prediktori OS-a. Usprkos statističkoj tendenciji morfološke karakteristike (podtip MDS-a, broj blasta u koštanoj srži) nisu se pokazale statistički značajnim čimbenicima prognoze u ovih bolesnika. Od kliničkih karakteristika jedino su prisutnost anemije i njezina težina, odnosno transfuzijska ovisnost bile znatno povezane s lošijim ishodom. Zaključak: Na našoj kohorti bolesnika većina tradicionalnih faktora pokazala se važnom u skladu s literaturnim podacima.Introduction: Myelodysplastic syndrome (MDS) is one of the most common myeloid neoplasms of elderly characterized by cytopenias and limited therapeutic options. The main aim of this retrospective singlecenter study was to examine the value of classical prognostic factors. The main outcome of the study was overall survival (OS) defined as death from MDS or any other reason. Methods: We analyzed the medical records of patients diagnosed with MDS at single centre in the period from beginning of 2013 to the end of 2016. Results: Total of 58 patients (median age of diagnosis being 69 years) were included in the study. After median of follow-up of 12 months, median OS was 17 months and estimated 3-year OS rate 25%. Classical prognostic systems such as IPSS, WPSS and R-IPSS were statistically significant prognostic factors discriminating adequately between low and high risk groups in terms of outcome. However , due to small sample size, we were not able to distinguish the most appropriate scoring system. The cytogenetics subgroups according to IPPS and R-IPSS were significant predictors of outcomes underlying its crucial role in MDS diagnosis. Despite the statistical tendency morphological features of MDS (2008 World Health Organization subtype and number of blasts in bone marrow) were not significant predictors of OS. Among clinical features, only presence and degree of anemia and transfusion dependency were significant predictors of inferior survival. Conclusion: The majority of traditional prognostic factors were significant in our cohort in concordance with literature review

The value of chromosomal findings in treatment of acute myeloid leukemia

U istraživanje je uključeno 536 bolesnika s novootkrivenom akutnom mijeloičnom leukemijom. Medijan dobi iznosio je 36 godine u rasponu od 16-60 godina. Akutna mijeloična leukemija M2 podtipa dijagnosticirana je u 31% slučajeva, dok je AML-M6 dijagnosticirana u 3% slučajeva. Akutna promijelocitna leukemija dijagnosticirana je u 76/536 (14%). Akutna mijeloična leukemija M4 podtipa dijagnosticirana je u 75/536 (14%), dok je AML-M5 dijagnosticirana u 62/536 (12%) bolesnika. Eritroleukemija (AML-M6) dijagnosticirana je u 18/536 (3%) bolesnika. Medijan leukocita pri dijagnozi iznosio je 19x109/L, raspona od 0.8-323x109/L. Za analizu kromosoma primjenjene su standardne metode pruganja. Prema nalazu citogenetske analize bolesnici su razdijeljeni u tri prognostičke skupine. Bolesnici s translokacijom t(8;21), inverzijom inv(16), translokacijom t(15;17) nalaze se u tzv. povoljnoj skupini. Bolesnici s urednim nalazom bez kromosomskih promjena u kariotipu odnosno bolesnici sa citogenetskim promjenama nepoznate prognoze čine posebnu skupinu intermedijarne prognoze. Bolesnici u kojih je nađena trisomija 8, ili promjene kromosoma 5, 7, promjene lokusa 11q23, 3q26 nalaze se u nepovoljnoj skupini. Citogenetske promjene nađene su u 363 (68%) bolesnika. Povoljan citogenetski nalaz nađen je u 118 (22%) bolesnika. Intermedijarni tip citogenetske promjene utvrđen je u 260 (49%) bolesnika, dok je u 158 (30%) bolesnika utvrđena nepovoljna citogentska promjena. Kompletna remisija postignuta je u 76% bolesnika dobre citogenetske prognoze, u 70% bolesnika intermedijarne citogenetske prognoze, te u samo 45% bolesnika nepovoljne citogenetske prognoze (p=0.001). Vjerojatnost petogodišnjeg preživljenja bez znakova bolesti u bolesnika s povoljnom, intermedijarnom i nepovoljnom citogenetskom promjenom iznosi 43%, 34% i 9% (p=0.05). Vjerojatnost relapsa bolesti iznosi 82% za bolesnike s nepovoljnom citogenetskom promjenom, 68% za bolesnike s intermedijarnom citogenetskom promjenom i 56% za bolesnike s povoljnim citogenetskim nalazom (p=0.05).In our investigation 536 patients with de novo acute leukemia were included into prospective study. Median age was 36 years, ranged 16-60. The majority of patients have AML-M2 (31%) or AML-M6 subtype (3%) according to French-American-British classification. 14% patients have AML-M3 subtype. AML-M4 was observed in 75/536 (14%) and AML-M5 in 62/536 (12%) patients. In 3% patients AML-M6 was documented. Median WBC at diagnosis was 19x109/l, ranged 0.-323x109/l. For chromosome analysis standard banding was done. According to the cytogenetic finding patients were classified in three prognostic groups. Patients with translocations t(8;21) or t(15;17), inversion inv(16) were classified as a good prognostic group, while patients with trisomy 8, patients with chromosome 3, 11q23 abnormalities and patients with changes of chromosome 5 and 7 were classified as a poor prognostic group. Other patients were classified as an intermediate prognostic group. Cytogenetic abnormalities were found in 363 (68%) patients. 22% patients were classified as a good prognostic group and 158 (30%) as a poor prognosis group. Complete remission was obtained in 76% of patients with good karyotype, in 70% patients with intermediate karyotype and only 45% in poor prognostic group (P=0.001). Five year probability of disease free survival for patients with good, intermediate and poor karyotype is 43%, 34% and 9% respectively (P=0.05). Probability of relapse for patients with poor karyotype is 82%, for intermediate karyotype 68% and for patients with good karyotype is 56% (P=0.05)

Prognostička vrijednost citogenetskih promjena u liječenju akutne leukemije [The value of chromosomal findings in treatment of acute myeloid leukemia]

In our investigation 536 patients with de novo acute leukemia were included into prospective study. Median age was 36 years, ranged 16-60. The majority of patients have AML-M2 (31%) or AML-M6 subtype (3%) according to French-American-British classification. 14% patients have AML-M3 subtype. AML-M4 was observed in 75/536 (14%) and AML-M5 in 62/536 (12%) patients. In 3% patients AML-M6 was documented. Median WBC at diagnosis was 19x109/l, ranged 0.-323x109/l. For chromosome analysis standard banding was done. According to the cytogenetic finding patients were classified in three prognostic groups. Patients with translocations t(8;21) or t(15;17), inversion inv(16) were classified as a good prognostic group, while patients with trisomy 8, patients with chromosome 3, 11q23 abnormalities and patients with changes of chromosome 5 and 7 were classified as a poor prognostic group. Other patients were classified as an intermediate prognostic group. Cytogenetic abnormalities were found in 363 (68%) patients. 22% patients were classified as a good prognostic group and 158 (30%) as a poor prognosis group. Complete remission was obtained in 76% of patients with good karyotype, in 70% patients with intermediate karyotype and only 45% in poor prognostic group (P=0.001). Five year probability of disease free survival for patients with good, intermediate and poor karyotype is 43%, 34% and 9% respectively (P=0.05). Probability of relapse for patients with poor karyotype is 82%, for intermediate karyotype 68% and for patients with good karyotype is 56% (P=0.05)

The value of chromosomal findings in treatment of acute myeloid leukemia

U istraživanje je uključeno 536 bolesnika s novootkrivenom akutnom mijeloičnom leukemijom. Medijan dobi iznosio je 36 godine u rasponu od 16-60 godina. Akutna mijeloična leukemija M2 podtipa dijagnosticirana je u 31% slučajeva, dok je AML-M6 dijagnosticirana u 3% slučajeva. Akutna promijelocitna leukemija dijagnosticirana je u 76/536 (14%). Akutna mijeloična leukemija M4 podtipa dijagnosticirana je u 75/536 (14%), dok je AML-M5 dijagnosticirana u 62/536 (12%) bolesnika. Eritroleukemija (AML-M6) dijagnosticirana je u 18/536 (3%) bolesnika. Medijan leukocita pri dijagnozi iznosio je 19x109/L, raspona od 0.8-323x109/L. Za analizu kromosoma primjenjene su standardne metode pruganja. Prema nalazu citogenetske analize bolesnici su razdijeljeni u tri prognostičke skupine. Bolesnici s translokacijom t(8;21), inverzijom inv(16), translokacijom t(15;17) nalaze se u tzv. povoljnoj skupini. Bolesnici s urednim nalazom bez kromosomskih promjena u kariotipu odnosno bolesnici sa citogenetskim promjenama nepoznate prognoze čine posebnu skupinu intermedijarne prognoze. Bolesnici u kojih je nađena trisomija 8, ili promjene kromosoma 5, 7, promjene lokusa 11q23, 3q26 nalaze se u nepovoljnoj skupini. Citogenetske promjene nađene su u 363 (68%) bolesnika. Povoljan citogenetski nalaz nađen je u 118 (22%) bolesnika. Intermedijarni tip citogenetske promjene utvrđen je u 260 (49%) bolesnika, dok je u 158 (30%) bolesnika utvrđena nepovoljna citogentska promjena. Kompletna remisija postignuta je u 76% bolesnika dobre citogenetske prognoze, u 70% bolesnika intermedijarne citogenetske prognoze, te u samo 45% bolesnika nepovoljne citogenetske prognoze (p=0.001). Vjerojatnost petogodišnjeg preživljenja bez znakova bolesti u bolesnika s povoljnom, intermedijarnom i nepovoljnom citogenetskom promjenom iznosi 43%, 34% i 9% (p=0.05). Vjerojatnost relapsa bolesti iznosi 82% za bolesnike s nepovoljnom citogenetskom promjenom, 68% za bolesnike s intermedijarnom citogenetskom promjenom i 56% za bolesnike s povoljnim citogenetskim nalazom (p=0.05).In our investigation 536 patients with de novo acute leukemia were included into prospective study. Median age was 36 years, ranged 16-60. The majority of patients have AML-M2 (31%) or AML-M6 subtype (3%) according to French-American-British classification. 14% patients have AML-M3 subtype. AML-M4 was observed in 75/536 (14%) and AML-M5 in 62/536 (12%) patients. In 3% patients AML-M6 was documented. Median WBC at diagnosis was 19x109/l, ranged 0.-323x109/l. For chromosome analysis standard banding was done. According to the cytogenetic finding patients were classified in three prognostic groups. Patients with translocations t(8;21) or t(15;17), inversion inv(16) were classified as a good prognostic group, while patients with trisomy 8, patients with chromosome 3, 11q23 abnormalities and patients with changes of chromosome 5 and 7 were classified as a poor prognostic group. Other patients were classified as an intermediate prognostic group. Cytogenetic abnormalities were found in 363 (68%) patients. 22% patients were classified as a good prognostic group and 158 (30%) as a poor prognosis group. Complete remission was obtained in 76% of patients with good karyotype, in 70% patients with intermediate karyotype and only 45% in poor prognostic group (P=0.001). Five year probability of disease free survival for patients with good, intermediate and poor karyotype is 43%, 34% and 9% respectively (P=0.05). Probability of relapse for patients with poor karyotype is 82%, for intermediate karyotype 68% and for patients with good karyotype is 56% (P=0.05)

The value of chromosomal findings in treatment of acute myeloid leukemia

U istraživanje je uključeno 536 bolesnika s novootkrivenom akutnom mijeloičnom leukemijom. Medijan dobi iznosio je 36 godine u rasponu od 16-60 godina. Akutna mijeloična leukemija M2 podtipa dijagnosticirana je u 31% slučajeva, dok je AML-M6 dijagnosticirana u 3% slučajeva. Akutna promijelocitna leukemija dijagnosticirana je u 76/536 (14%). Akutna mijeloična leukemija M4 podtipa dijagnosticirana je u 75/536 (14%), dok je AML-M5 dijagnosticirana u 62/536 (12%) bolesnika. Eritroleukemija (AML-M6) dijagnosticirana je u 18/536 (3%) bolesnika. Medijan leukocita pri dijagnozi iznosio je 19x109/L, raspona od 0.8-323x109/L. Za analizu kromosoma primjenjene su standardne metode pruganja. Prema nalazu citogenetske analize bolesnici su razdijeljeni u tri prognostičke skupine. Bolesnici s translokacijom t(8;21), inverzijom inv(16), translokacijom t(15;17) nalaze se u tzv. povoljnoj skupini. Bolesnici s urednim nalazom bez kromosomskih promjena u kariotipu odnosno bolesnici sa citogenetskim promjenama nepoznate prognoze čine posebnu skupinu intermedijarne prognoze. Bolesnici u kojih je nađena trisomija 8, ili promjene kromosoma 5, 7, promjene lokusa 11q23, 3q26 nalaze se u nepovoljnoj skupini. Citogenetske promjene nađene su u 363 (68%) bolesnika. Povoljan citogenetski nalaz nađen je u 118 (22%) bolesnika. Intermedijarni tip citogenetske promjene utvrđen je u 260 (49%) bolesnika, dok je u 158 (30%) bolesnika utvrđena nepovoljna citogentska promjena. Kompletna remisija postignuta je u 76% bolesnika dobre citogenetske prognoze, u 70% bolesnika intermedijarne citogenetske prognoze, te u samo 45% bolesnika nepovoljne citogenetske prognoze (p=0.001). Vjerojatnost petogodišnjeg preživljenja bez znakova bolesti u bolesnika s povoljnom, intermedijarnom i nepovoljnom citogenetskom promjenom iznosi 43%, 34% i 9% (p=0.05). Vjerojatnost relapsa bolesti iznosi 82% za bolesnike s nepovoljnom citogenetskom promjenom, 68% za bolesnike s intermedijarnom citogenetskom promjenom i 56% za bolesnike s povoljnim citogenetskim nalazom (p=0.05).In our investigation 536 patients with de novo acute leukemia were included into prospective study. Median age was 36 years, ranged 16-60. The majority of patients have AML-M2 (31%) or AML-M6 subtype (3%) according to French-American-British classification. 14% patients have AML-M3 subtype. AML-M4 was observed in 75/536 (14%) and AML-M5 in 62/536 (12%) patients. In 3% patients AML-M6 was documented. Median WBC at diagnosis was 19x109/l, ranged 0.-323x109/l. For chromosome analysis standard banding was done. According to the cytogenetic finding patients were classified in three prognostic groups. Patients with translocations t(8;21) or t(15;17), inversion inv(16) were classified as a good prognostic group, while patients with trisomy 8, patients with chromosome 3, 11q23 abnormalities and patients with changes of chromosome 5 and 7 were classified as a poor prognostic group. Other patients were classified as an intermediate prognostic group. Cytogenetic abnormalities were found in 363 (68%) patients. 22% patients were classified as a good prognostic group and 158 (30%) as a poor prognosis group. Complete remission was obtained in 76% of patients with good karyotype, in 70% patients with intermediate karyotype and only 45% in poor prognostic group (P=0.001). Five year probability of disease free survival for patients with good, intermediate and poor karyotype is 43%, 34% and 9% respectively (P=0.05). Probability of relapse for patients with poor karyotype is 82%, for intermediate karyotype 68% and for patients with good karyotype is 56% (P=0.05)

COEXISTENCE OF TRISOMY 12 AND DEL(13)(Q14.3) IN TWO PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA

Abstract — We describe two patients with diagnosis of chronic lymphocytic leukemia (CLL) in whom interphase fluorescence in situ hybridization (FISH) analysis revealed trisomy 12 and del(13)(q14.3) occurring in the same clone. These abnormalities are rarely seen together and the prognostic relevance of their coexistence is still unclear. According to some data, a probable adverse prognosis for this group of patients is suggested. Our patients have been in a stable phase of the disease for more than one year since the given abnormalities were documented in their karyotypes. Further study is necessary to determine the prognostic significance of coexistence of these abnormalities in CLL patients