Metastasis of solid tumors into bone marrow – Single center experience

Introduction: Metastases of solid tumors to the bone marrow are rarely reported. Clinical manifestation and laboratory findings remain uncharacteristic and lead to misdiagnosis. Detection of bone marrow metastases may have an impact on therapeutic decisions and is usually associated with poor prognosis. Aim: To characterize clinical picture and hematological findings in patients with bone marrow metastasis. Material and methods: We retrospectively reviewed medical records of patients with bone marrow metastases who were primary misdiagnosed with hematological malignancies. Results: Ten patients at median age of 51 years at diagnosis were included. There were following findings on admission: duopenia (n=7), pancytopenia (n=1), anemia (n=1) and skeletal lytic lesions (n=1). The diagnosis of prior cancer was reported in 3 patients and included multiple myeloma, breast cancer and oligoastrocytoma. Clinical manifestations were hepatomegaly (n=4), lymphadenopathy (n=4), skin pallor (n=3), cachexia (n=2) and hemorrhagic diathesis (n=2). Imaging studies revealed diffuse bone lesions (n=5), pulmonary infiltrates (n=2) and liver masses (n=2). Leukoerythroblastosis was demonstrated in 4 cases. Bone marrow aspirate detected the presence of abnormal cell population in 4 patients. In all studied patients a final diagnosis was established by immunohistochemistry of bone marrow biopsy. The following malignancies were detected: prostate adenocarcinoma (n=2), anaplastic microcellular carcinoma of unknown origin (n=2), adenocarcinoma of unknown origin (n=2), Ewing's sarcoma (n=1), breast cancer (n=1), clarocellular renal cancer (n=1) and neuroendocrine tumor (n=1). Nine out of the 10 metastatic patients died shortly after chemotherapy. Conclusions: Unexplained hematological abnormalities should arise the suspicion of bone marrow metastases

Results of Polish Adult Leukemia Study Group (PALG) project assessing TP53 mutations with next-generation sequencing technology in relapsed and refractory chronic lymphocytic leukemia patients — an 18-month update

Indtroduction and methods: In chronic lymphocytic leukemia (CLL), molecular and cytogenetic diagnostics are crucial for the determination of accurate prognosis and treatment choice. Among different genetic aberrations, del(17p13) or TP53 mutations constitute high-risk factors, and early identification of such defects is a high priority for CLL patients. While cytogenetic diagnostics is well-established and accessible for the majority of CLL patients in Poland, molecular diagnostics of TP53 mutations is performed only in a few ERIC-certified centers (eight as of September 2020), and only two of these employ next-generation sequencing (NGS) for routine analysis of TP53 status in CLL patients. Here we report the interim results of a project assessing TP53 mutations with NGS technology in relapsed or refractory CLL patients with confirmed negative del(17p13) status. 249 patients from 32 clinical centers were included in the study. Results: NGS analysis revealed TP53 mutations in 42/249 (17%) patients, half of whom (21/249, 8.5%) had subclonal mutations (VAF ≤10%). These results are in line with published data in relapsed/refractory CLL patients. Conclusions: The results of the project demonstrated the feasibility and accuracy of NGS testing in CLL patients despite several initial logistical and technical obstacles. Our study also proved that, with appropriate funding, CLL patients from any hematological center in Poland can have access to state-of-the-art molecular diagnostic

Late relapse of chronic myeloid leukemia after allogeneic stem cell transplantation – a case report

Chronic myeloid leukemia now is a disease which in the most cases is well manageable with tyrosine kinase inhibitors treatment. Still however the only potentially curable therapeutic approach is for chronic myeloid leukemia allogeneic stem cell transplantation. 30-years old woman was diagnosed as a relapse 18 years after sibling matched donor allotransplantation. After a short cytoreductive treatment imatinib was given in standard dose. Then due to hematological toxicities the dose was diminished to 100 mg. The patient has maintained major molecular response since 2,5 years.Przewlekła białaczka szpikowa obecnie w większości przypadków jest chorobą dobrze poddającą leczeniu inhibitorami kinazy tyrozynowej. Nadal jednak jedyną procedurą leczniczą dającą możliwość wyleczenia jest aloprzeszczepienie komórek macierzystych. U 30-letniej pacjentki 18 lat po aloprzeszczepieniu od dawcy rodzinnego z powodu przewlekłej białaczki szpikowej stwierdzono wznowę choroby. Po leczeniu cytoredukcyjnym włączono standardową dawkę imatynibu. Z powodu toksyczności hematologicznej zmniejszano ją do obecnej – 100 mg/24 h. Po 2,5 roku leczenia u pacjentki utrzymuje się pogłębiająca się większa odpowiedź molekularna

Pacjent z przewlekłą białaczką limfocytową z licznymi powikłaniami po wcześniejszych liniach leczenia i wieloma powikłaniami obecnie w trakcie terapii wenetoklaksem w skojarzeniu z rytuksymabem

U 67-letniego pacjenta z przewlekłą białaczką limfocytową po 15 latach od rozpoznania wystąpiła kolejna progresja choroby po 10. linii leczenia. Wcześniej pacjent otrzymywał chemioterapię, immunoterapię oraz leczenie celowane ibrutynibem. Pacjent był obciążony udarem krwotocznym oraz wymagał w przeszłości żywienia przez gastrostomię. Z powodu kolejnej progresji choroby i stwierdzenia delecji w obrębie chromosomu 17 pacjent został zakwalifikowany do leczenia rytuksymabem i wenetoklaksem, który następnie stosowano w monoterapii. Leczenie to poprawiło stan kliniczny pacjenta, prowadząc do całkowitej remisji. Nie obserwowano poważnych zdarzeń niepożądanych związanych z leczeniem, jednak w trakcie terapii pacjent przebył zakażenie wirusem SARS-CoV-2. Przebieg zakażenia był umiarkowany, a pacjent nie wymagał hospitalizacji; na czas zakażenia przerwano jednak terapię wenetoklaksem. Podsumowując, wenetoklaks jest skutecznym lekiem w nawracającej lub opornej przewlekłej białaczce limfocytowej również u pacjentów leczonych wcześniej innymi lekami celowanymi

OCCURRENCE OF SECONDARY MALIGNANCIES IN CHRONIC MYELOID LEUKEMIA DURING THERAPY WITH IMATINIB MESYLATE-SINGLE INSTITUTION EXPERIENCE

Introduction. Imatinib mesylate (IM) remains a treatment of choice for chronic myeloid leukemia (CML) showing a remarkable efficacy and providing a perspective for a long disease-free survival. Due to the long-term administration of IM, the questions about the possible impact on the development of secondary malignancies (SM) are raised. Objective. To investigate the frequency and clinical outcome of secondary malignancies during IM therapy for CML. Material and Methods. The records of 221 CML patients treated with IM between 2003-2013 in single institution were reviewed. The Chi-squared test was used for statistic analysis. Results. Secondary malignancies developed in eight out of the 221 patients (3.6%) receiving IM for a median of 61 months (range, 10-137 months). Female/male ratio was 5/3. Two patients were diagnosed with their CML at accelerated phase whereas 6 had chronic phase. The median age at IM initiation was 58 years (range, 31-72 years).  Five of these 8 SM patients received IM after other treatments failure: interferon α (n=5), hydroxyurea (n=4) and cytarabine (n=1). Three patients received IM as a frontline therapy. All patients were on IM at 400mg daily at SM occurrence. The therapy for SM included surgery (n=3); chemotherapy only (n=3); and chemotherapy followed by radiotherapy (n=1). One patient did not receive treatment due to disseminated disease. At the time of SM development all patients were in hematologic and cytogenetic remission (CCR) of their CML and all patients continued their IM while receiving treatment for their SM.  Among 8 patients with SM, five patients are alive and remain in CCR on IM whereas 3 patients died due to SM. The observed incidence of SM was found to be comparable with that expected in the age-adjusted population (chi-squared=0.4; p=0.52). Conclusions. The association between IM therapy for CML and SM development has not been found