A small subgroup of patients with hypereosinophilic syndrome (HES) demonstrates imatinib-sensitive fusion transcript-the FIP1L1-PDGFRA (F/P+). These cases are currently diagnosed as chronic eosinophilic leukaemia (CEL). In this paper, we screened 77 patients to estimate the frequency of FIP1L1-PDGFRA transcript among patients with unexplained, long-term hypereosinophilia exceeding 1.5 x 10(9)/L and to analyse the clinical and serological features in F/P+ CEL population. The FIP1L1-PDGFRA chimeric protein was detectable in 16 (14 males and 2 females) out of 77 examined HES patients (20%) by RT-PCR. Two patients suffered from cough at diagnosis. Three out of 16 (18%) patients had no organ involvements, in 5-one organ was affected and in the remaining eight cases-at least two. Eosinophilic organ damage/dysfunction identified splenomegaly in the majority of studied patients. We compared clinical and serological features between CEL F/P+ (n = 16) and HES (n = 61) patients. F/P+ cases had significantly increased WBC and absolute eosinophil count (AEC) at diagnosis (p = 0.008 and 0.02), whereas platelet count was decreased in this population (p = 0.03). Serum B12 and tryptase levels were increased (p = 0.002 and 0.004) in CEL F/P+ patients when compared to HES cases whereas serum IL-5 levels were significantly increased in the latter group (p = 0.01). Male gender and splenomegaly occurred more frequent in CEL F/P+ population (p = 0.002 and 0.0007, respectively). Additionally, patients with F/P+ CEL (n = 16) were compared with F/P- CEL (n = 8). The latter group, was significantly older, had lower AEC and higher platelet count. In conclusion, significant clinical symptoms are infrequent present and splenomegaly remains the most common organ involvement in patients with CEL expressing F/P fusion transcript. Our study confirmed the long-term remission on imatinib in this patient population.

The idiopathic hypereosinophilic syndrome (HES) comprises a heterogenous group of disorders characterized by marked blood eosinophilia with eosinophilia-associated organ damage. Eight patients with a median age at diagnosis of 42 years (range 19-67) received imatinib mesylate (IM) for FIP1L1-PDGFRα-negative HES resistant to previous conventional treatment. Median number of prior therapies was 3 (range 2-4). Median time from diagnosis to IM initiation was 112 months (range 2-293). Four patients were treated daily with 100 mg IM, whereas the remaining four patients were treated daily with 400 mg IM. Four male patients (50%) achieved complete haematologic response (CHR) after median of 7 days (range 3-150) using 100 mg daily IM (n = 2) and 400 mg (n = 2). Median duration of IM treatment for IM responders was 18 months (range 2-88). No adverse events were reported throughout the treatment duration. Two patients maintained CHR while on 100 mg weekly IM. Four patients (2 men and 2 women) failed IM treatment. Median duration of IM for non-responding patients was 3 weeks (range 3-12). Non-responding HES patients were significantly older and had lower percentage of blood eosinophilia when compared with IM responders. Our results suggest that IM, even at lower than conventional doses, may induce and maintain long-term remission for FIP1L1-PDGFRα-negative HES.

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StreszczenieInhibitory kinaz tyrozynowych (TKI) II generacji pozwalają uzyskać bardzo dobry efekt leczenia u znacznego odsetka chorych z przewlekłą białaczką szpikową (CML) po niepowodzeniu leczenia imatynibem (IM). Leki te, na ogół dobrze tolerowane, mają charakterystyczne profile toksyczności, a ich zaletą jest niewielka krzyżowa nietolerancja. W artykule opisano przypadek pacjenta od 10 lat leczonego z powodu CML, początkowo IM, a następnie z powodu niepowodzenia leczenia stwierdzonego w 18 miesiącu terapii -dazatynibem. Po 6 latach, z powodu nawracającego płynu w jamach opłucnowych, wymuszającego zmniejszanie dawki (do 80 mg/d., a następnie do 50 mg/d.) i przerwy w leczeniu, doszło do utraty większej odpowiedzi molekularnej (MMR). Z tego powodu u chorego włączono do terapii nilotynib. W chwili wdrożenia tego leku stwierdzono obecność czynników ryzyka chorób układu sercowo-naczyniowego w postaci nadciśnienia tętniczego, hipercholesterolemii i otyłości brzusznej. Pacjent po 3 miesiącach uzyskał MMR, a po 18 miesiącach -głęboką odpowiedź molekularną (MR4,0). Nie doszło do pojawienia się żadnych objawów niepożądanych w stopniu wymagającym przerwania leczenia nilotynibem bądź zmniejszenia dawki. Pacjent przestrzega zaleceń dotyczących stosowania TKI, a także korekty modyfikowalnych czynników ryzyka sercowo-naczyniowego. Słowa kluczowe: przewlekła białaczka szpikowa, imatynib, dazatynib, nilotynib, działanie niepożądane, stosowanie się do zaleceń Hematologia 2017; 8, supl. B: B5-B10Abstract Second-generation tyrosine kinase inhibitors (TKI), have shown high efficacy for patients with imatinib (IM) resistence or intolerance. Lack of cross-intolerance is an important advantage of TKI 2 nd generation. Unfortunatelly they have significant side effects. The case of a patient treated since last 10 years due to chronic myelogenous leukemia has been described. He was prescribed dasatinib in second-line and achived major molecular response (MMR) at 18 month. After 6 years, due to recurrent pleural effusion, which was the reason for dose reduction and treatment interruptions, loss of MMR occurred. Next drug used was nilotinib. At the begining of treatment Adres do korespondencji: B6 Hematologia 2017, tom 8, supl. B www.hematologia.viamedica.pl cardiovascular risk factors (arterial hypertension, and obesity) were present. After 3 months MMR and after 18 months -deep molecular response was achieved. Any side effect which would force to treatment interruption or dose reduction hasn't occured till now. Patient adheres to the recomendations, including correction of modifiable cardiovascular risk factors.