Autologiczna transplantacja komórek krwiotwórczych u chorych na szpiczaka plazmocytowego w dobie nowych terapii

Autologiczna transplantacja komórek krwiotwórczych (AHSCT) należy do standardowych metod leczniczych u chorych na szpiczaka plazmocytowego (MM) od ponad 30 lat. Wprowadzenie do terapii nowych leków (inhibitory proteasomu, leki immunomodulacyjne, przeciwciała monoklonalne) radykalnie zmieniło główne zasady leczenia. W artykule podjęto próbę określenia miejsca AHSCT w aktualnym algorytmie terapii chorych na MM

Ruksolitynib w leczeniu pierwotnej mielofibrozy w fazie akceleracji i z małopłytkowością – opis przypadku

Pierwotna mielofibroza ( – PMF) jest Ph-negatywnym nowotworem mieloproliferacyjnym, charakteryzującym się włóknieniem szpiku, cytopeniami oraz objawami ogólnymi, które w istotny sposób wpływają na jakość i długość życia. Stosowanie ruksolitynibu, inhibitora kinaz JAK1 i JAK2 prowadzi do zmniejszenia wymiarów śledziony, a także nasilenia objawów ogólnych, co poprawia jakość życia. Tego typu terapia rekomendowana jest u chorych z objawową mielofibrozą z grupy ryzyka pośredniego 2 i wysokiego. Opublikowano dotąd niewiele doniesień dotyczących zastosowania ruksolitynibu w zaawansowanych fazach PMF: akceleracji i zaostrzenia blastycznego. Ważnym klinicznie problemem jest także prowadzenie chorych ze współistniejącą małopłytkowością.W pracy przedstawiono chorą na PMF, u której ruksolitynib z dobrym skutkiem stosowany jest od 4 lat w fazie akceleracji, przy współistniejącej małopłytkowości. Rozpoznanie PMF postawiono w 2008 r. W ciągu piewszych 5 lat w leczeniu stosowano hydroksykarbamid, talidomid, prednizon i radioterapię śledziony. W roku 2013 rozpoznano akcelerację choroby, charakteryzującą się obecnością 10% blastów w szpiku, splenomegalią dużego stopnia, małopłytkowością oraz nasileniem objawów ogólnych. Leczenie ruksolitynibem rozpoczęto w grudniu 2013 r. Dawka leku, zależnie od liczby płytek krwi, wahała sie od 5 mg raz dziennie do 20 mg 2 razy dziennie. Terapia ruksolitynibem jest kontynuowana do dzisiaj, tj. ponad 4 lata. Jej efektem jest redukcja wymiarów śledziony, ustąpienie objawów ogólnych, poprawa jakości życia oraz stabilizacja odsetka komórek blastycznych w szpiku. Prezentowany przypadek jest przykładem na skuteczność ruksolitynibu w fazie zaawansowanej PMF dzięki indywidualizacji dawkowania leku

The role of hematopoietic stem cell transplantation in the treatment of patients with plasma cell myeloma

Autologiczne przeszczepienie macierzystych komórek krwiotwórczych (auto-HSCT) nadal jest standardową metodą w leczeniu I linii u chorych na szpiczaka plazmocytowego (PCM) w wieku poniżej 65 lat. Nowe leki, takie jak talidomid, lenalidomid i bortezomib, stosuje się na wszystkich etapach terapii, w tym w okresach: indukcji, kondycjonowania, konsolidacji i podtrzymywania. Efektem jest większy odsetek całkowitych remisji (CR) przed i po transplantacji oraz wydłużenie czasu przeżycia chorych. Transplantacja allogeniczna (allo-HSCT) nadal stanowi opcję eksperymentalną. Z powodu dużej śmiertelności po transplantacji mieloablacyjne kondycjonowanie jest obecnie zastępowane przez kondycjonowanie o ograniczonej intensywności (RIC), co wykonuje się po wcześniejszej transplantacji autologicznej zmniejszającej masę guza. Hematologia 2011; 2, 2: 131–139Autologous hematopoietic stem cell transplantation (auto-HSCT) is still standard method in the frontline therapy of patients with plasma cell myeloma younger than 65 years. Novel agents, e.i. thalidomide, lenalidomide, bortezomib are incorporated into all phases of therapy, including: induction, conditioning, consolidation and maintenance. It results in higher preand posttransplantation complete remission (CR) rates and leads to a longer overall survival. Allogeneic transplantation (allo-HSCT) is still only an investigational procedure. Because of high transplantation-related mortality myeloablative allografting is replaced by reduced-intensity conditioning (RIC) after a debulky autologous transplantation. Hematologia 2011; 2, 2: 131–13

Primary myelofibrosis – review of therapeutic methods

Primary myelofibrosis (PMF) is a Ph-negative myeloproliferative neoplasm (MPN), that manifests bone marrow fibrosis, cytopenias, splenomegaly, and constitutional symptoms. The conventional therapeutic options for patients with PMF consist of management of anemia, use of cytoreductive and immunomogulatory agents, and splenectomy or splenic irradiation. Cure is only achievable through allogeneic haematopoietic stem cell transplantation. The discovery of crucial role of JAK2 signaling in pathogenesis of PMF has resulting in new JAK2 inhibitor therapy, such ruxolitinib or other investigated molecules

Leukaemic stem cells

Acute myeloid leukaemia (AML) is a neoplasm originating in early haematopoietic progenitor cells. Each AML clone contains a subpopulation of leukaemic stem cells (LSCs). LSCs have the capacity to repopulate AML in NOD/SCID mice and regrow leukaemia in patients after remission period. LSCs are characterized by CD34+CD38-Lin-CD33+/-CD123+ immunophenotype. The currently available data show that LSCs play a pivotal role in drug resistance. Many studies and clinical trials are being conducted to eradicate LSCs using different forms of target therapy

Imatinib therapy of Ph positive acute lymphoblastic leukaemia – 2 case reports

AimThe aim of this works is the presentation of two cases of relapsed Ph positive acute lymphoblastic leukaemia (ALL) to which the tyrosine inhibitor Imatinib (Glivec, Novartis) was applied. This therapy was earlier shown to be very helpful in the treatment of chronic myeloid leukemia.Case discriptionCase 1: A 17 year old patient with Ph positive T-ALL relapsed after allogenic transplantation of marrow and was treated with Imatinib in escalating doses from 200 to 600 mg per day. After 4 weeks of treatment the blastosis in the marrow had fallen from 96% to 7%. Blasts disappeared from the cerebrospinal fluid. At the same time, progression of hepatic and renal failure related to GVHD was observed. Imatinib withdrawal resulted in relapse, uncontrolled proliferation and the death of the patient.ResultsCase 2: Imatinib was used in the case of a 45 year old patient with Ph positive null-ALL and a mediastinal tumour. After autologous bone marrow transplantation, Imatinib therapy was begun for maintenance.. Daily doses of the drug amounted to only 200 mg owing to associated gastric complaints. After two months of therapy, an increase in blast cells in the bone marrow to 18% was noted. FLAM chemotherapy was given and complete haematological remission was achieved.ConclusionsThe cases described illustrate new possibilities in the treatment of Ph positive ALL. It is necessary, however, to conduct clinical trials in larger group of patients for the purposes of establishing optimal dosing, the most suitable phase of the disease in which to begin therapy and possible combinations with chemotherapy

The activity of human telomerase in the cells of acute leukaemias

Telomeres are the end fragments of chromosomes formed by a number of non-coding double-stranded TTAGGG repeats in vertebrates. During cell division the number of repeats decreases, leading to cell senescence or apoptosis. In immortal cells, including cancer cells, the telomere length is stable and maintained by, among other factors, telomerase. The aim of the study is to compare telomerase activity in normal lymphocytes and in leukaemic cells. Samples of acute leukaemia cells, HL 60 cell line and the lymphocytes of healthy volunteers were examined. Telomerase analysis was performed using TeloTAGGG Telomerase PCR ELISAplus (Roche). The relative telomerase activities (RTA) in leukaemic and normal cells were analysed. A high level of RTA was observed in leukaemic cells

Personalized therapy for patients with follicular lymphoma in era of rituximab

In patients with follicular lymphoma (FL), there are several factors influencing the disease course: morphological, immunological, genetic and clinical. The therapeutic options for patients with FL contain many methods such as rituximab with different chemotherapy regimens, radioimmunotherapy, radiotherapy and hematopoietic stem cell transplantation. The modern management of FL patients should consist of personalization of therapy related to risk factors

Central nervous involvement by chronic lymphocytic leukaemia

Inclusion of the central nervous system (CNS) in the course of chronic lymphocytic leukaemia (CLL) is rare. At the moment no risk factors or proven treatment methods are known. The disease is described both in its early phase and during its acceleration period, thus it has been suggested that there might be independent mechanisms influencing the development of this condition. As there are no unified diagnostic procedure algorithms each patient needs to be assessed individually. CLL can manifest mostly in elderly people, for whom a possibility of development of neurological disorders with their aetiology different from leukaemia, should also be taken into consideration. The thesis presents a group of seven patients with CLL with CNS infiltration. Patients with prolymphocytic leukaemia, Richter's transformation and the original location of leukemic infiltration within the eye socket constitute an especially interesting case

Treatment of multiple myeloma patients with autologous stem cell transplantation — a fresh analysis

Patients with multiple myeloma (MM) treated with conventional chemotherapy have an average survival of approximately three years. High dose chemotherapy followed by autologous stem cell transplantation (ASCT), first introduced in the mid-1980s, is now considered the standard therapy for almost all patients with multiple myeloma, because it prolongs overall survival and disease free survival. Between November 1997 and October 2006, 122 patients with MM (58 females, 64 males, median age 51.0 years [± 7.98] range: 30–66 years) were transplanted in the Department of Hematooncology and Bone Marrow Transplantation at the Medical University of Lublin: 47 patients were in complete remission or in unconfirmed complete remission, 66 patients were in partial remission, and nine had stable disease. Of these, there were 95 patients with IgG myeloma, 16 with IgA myeloma, one with IgG/IgA, one with IgM myeloma, five with non secretory type, two with solitary tumor and two with LCD myeloma. According to Durie-Salmon, 62 patients had stage III of the disease, 46 had stage II and four had stage I. Most patients (69/122) were transplanted after two or more cycles of chemotherapy, 48 patients were transplanted after one cycle of chemotherapy, one patient after surgery and rtg- -therapy and four patients had not been treated. In mobilisation procedure, the patients received a single infusion of cyclophosphamide (4–6 g/m2) or etoposide 1.6 g/m2 followed by daily administration of G-CSF until the peripheral stem cells harvest. The number of median harvest sessions was 2.0 (± 0.89) (range: 1–5). An average of 7.09 (± 33.28) × 106 CD34+ cells/kg were collected from each patient (range: 1.8–111.0 × 106/kg). Conditioning regimen consisted of high dose melphalan 60–210 mg/m2 without TBI. An average of 3.04 (± 11.59) × 106 CD34+ cells/kg were transplanted to each patient. Fatal complications occured in four patients (treatment- -related mortality = 3.2%). In all patients there was regeneration of hematopoiesis. The median number of days for recovery to ANC > 0.5 × 109/l was 13 (± 4.69) (range: 10–38) and platelets recovery to > 50 × 109/l was 25 days (± 11.65) (range: 12–45). Median time of hospitalization was 22 days (± 7.14) (range: 14–50). Patients were evaluated on day 100 after transplantation: 74.9% achieved CR and nCR, 14.3% were in PR, 5.4% had SD and 5.4% had progressed. Median of OS was 45 months (± 30.67). OS at 3-years was 84% and at 7-years 59%. Median PFS was 25 months (± 26.13). PFS at 3-years was 68%, and at 7-years was 43%. At present (November 2009) 52 patients (42%) are still alive. High-dose chemotherapy followed by autologous stem cell transplantation is a valuable, well tolerated method of treatment for patients with MM that allows the achievement of long- -lasting survival. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 248–254