לוקמיה מסוג apl

אמי בת 62 לפני כשלוש שנים חלתה במחלת הלוקמיה מסוג apl. קיבלה 3 טיפולים כימותרפיים ולאחר מכן בוצע איסוף תאי אב. לפני כחודש המחלה חזרה. הרופאים המטפלים בה החליטו על טיפול בארסן עד להגעה לרימיסיה ולאחר מכן מייעדים טיפול כימותרפי אחד חזק ע"מ לבצע השתלת מח עצם עצמית. שאלתי היא: האם לא ניתן להסתפק בטיפול בארסן בלבד ומה ההשלכות? הבנתי כי במקרים רבים המחלה חזרה גם לאחר השתלת מח עצם עצמית, האם ישנה אפשרות לבדוק את התאים השמורים, או אולי ישנו פתרון אחר. כל הזמן אומרים לנו שסוג הלוקמיה הזה יחסית קל? אנא השב לשאלותיי ואם יש לך דיעה נוספת בעניין נשמח לשמוע.

ראשית - קראי את התשובה שכתבתי בנושא ארסן ואת המקורות שצרפתי http://doctors.msn.co.il/forums/read.php?f=81&i=58966&t=58801 שנית - כמובן שלא אוכל להביע דעה בנושא הטיפול הרצוי במקרה הפרטני. באופן עקרוני, אין הוכחות ברורות מחקריות שיש עדיפות להשתלת מח עצם עצמית לאחר כניסה לרמיסיה שניה ב- APL. יש מחקרים ראשוניים מעודדים בנושא זה כפי שתקראי בציטוטים הבאים, אבל עדיין לא מסקנות חד משמעיות באשר לעדיפות מסלול זה. בדיקת כל התאים המוקפאים בודאי אינה אפשרית. בכל מקרה - ההנחה היא שרוב מכריע של התאים שנאספו במהלך רמיסיה אינו נושא את המחלה, וגם אם יש תאים בודדים פגועים הם יוכרעו ע"י הטיפולים או מערכת החיסון. השתלה עצמית כזו מאפשרת מתן כמויות גבוהות של כימותרפיה ומגדילה את הסיכוי שכל התאים הנגועים הושמדו. אני מדגיש שוב שאיני אומר שזו דרך הטיפול המומלצת במקרה זה והמידע הינו כללי. Acta Haematol 2002;107(1):1-17 Advances in the treatment of relapsed acute promyelocytic leukemia. Douer D. Division of Hematology, Keck School of Medicine, USC/Norris Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA. [email protected] The presence of the characteristic fusion transcript gene, promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARalpha), provided hematologists with a rationale for the use of all-trans retinoic acid (ATRA) for differentiation therapy for acute promyelocytic leukemia (APL). Multiple studies have established that combination of ATRA and chemotherapy in newly diagnosed patients has increased the cure rate to 70% from 35% in patients treated with chemotherapy alone. However, still about 30% of the patients relapse and are often resistant to ATRA retreatment. Consequently, a number of novel agents that include several differentiation agents and monoclonal antibodies have been studied to provide improved outcomes for patients with APL who have relapsed. In particular, arsenic trioxide has shown great promise for the induction, consolidation, and maintenance of complete remission in relapsed patients with APL. The unique mechanisms of action by which arsenic trioxide exerts its effects are complementary to those of ATRA, potentially allowing for combination therapies with additive or even synergistic results. Within this context autologous or allogeneic bone marrow transplantations are also considered in second or subsequent relapse, especially after arsenic trioxide-induced complete remission in relapsing patients. Furthermore, molecular monitoring for the PML-RARalpha fusion protein permits prompt intervention for early molecular relapse of APL before clinical relapse, ultimately improving chances of prolonged remission. Copyright 2002 S. Karger AG, Basel -------------------------------------------------------------------------------- Bone Marrow Transplant 2001 Aug;28(3):219-26 The role of bone marrow transplantation in acute promyelocytic leukemia. Nabhan C, Mehta J, Tallman MS. Division of Hematology-Oncology, Department of Medicine, Northwestern University Medical School, Robert H Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA. Acute promyelocytic leukemia (APL) is characterized by a specific gene rearrangement and the generation of the PML-RARalpha fusion transcript which results from a translocation between chromosomes 15 and 17. Targeted therapy with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy results in an apparent cure in 70-80% of patients. Both allogeneic (ALLO) and autologous (AUTO) hematopoietic stem cell transplantation (HSCT) are effective in acute myeloid leukemia (AML), but their role in APL is not clear given the excellent outcome with ATRA and chemotherapy. Several retrospective studies have analyzed the outcome of patients undergoing AUTO or ALLO-HSCT in first (CR1) or second (CR2) complete remission. Most of these studies have shown significant transplant-related mortality (TRM) with ALLO-HSCT, but a reduction in relapse rate compared with AUTO-HSCT. The high TRM with ALLO-HSCT and the excellent outcome with ATRA and chemotherapy do not justify recommending this procedure for the majority of patients in CR1. The role of AUTO-HSCT in CR1 also is unclear. A small subset of patients at high risk of relapse, possibly identifiable by a high white blood cell count at presentation may benefit from HSCT. Most patients with relapsed disease achieve CR2 with ATRA, arsenic trioxide, or combination therapy. However, it is not known if these responses are sustained or if consolidation with HSCT has a place in this setting. The outcome of AUTO-HSCT in CR2 using stem cells that are negative for PML-RARalpha is excellent. It is unclear whether ALLO-HSCT from an HLA-identical sibling is superior to AUTO-HSCT with PML-RARalpha-negative cells in CR2 since the former would be associated with graft-versus-leukemia effects and the latter with lower TRM. Alternatively, arsenic trioxide or re-treatment with ATRA, followed by intensive chemotherapy may also be effective. A randomized prospective clinical trial, or a retrospective analysis of the available data would be useful in answering this critical question. -------------------------------------------------------------------------------- Leukemia 2000 Jun;14(6):1006-13 Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic acid therapy followed by timed sequential chemotherapy and stem cell transplantation. APL Study Group. Acute promyelocytic leukemia. Thomas X, Dombret H, Cordonnier C, Pigneux A, Gardin C, Guerci A, Vekhoff A, Sadoun A, Stamatoullas A, Fegueux N, Maloisel F, Cahn JY, Reman O, Gratecos N, Berthou C, Huguet F, Kotoucek P, Travade P, Buzyn A, de Revel T, Vilque JP, Naccache P, Chomienne C, Degos L, Fenaux P. Department of Hematology, Hopital Edouard Herriot, Lyon, France. The purpose of this study was to assess the safety and efficacy of stem cell transplantation (SCT) mainly autologous SCT as consolidation therapy in APL patients who relapsed and achieved a second complete remission (CR2). Fifty adult patients with a first relapsed APL, of whom 39 had been previously treated with ATRA, entered a multicenter trial of oral ATRA until complete remission (CR) achievement followed by timed sequential chemotherapy (EMA combining etoposide 200 mg/m2/day for 3 days, mitoxantrone 12 mg/m2/day for 3 days, and cytarabine 500 mg/m2/day for two sequences of 3 days). EMA was started either after CR achievement, or on day 1 of ATRA because of initial white blood cell (WBC) counts >5 x 10(9)/l, or rapidly added to ATRA in order to prevent ATRA syndrome because WBC count increased under ATRA. Forty-five patients (90%, 95% CI 78%-97%) were in CR after induction therapy. Five patients died from infection during aplasia following EMA chemotherapy. Eleven patients who achieved CR had a familial HLA-identical donor and were allografted. The median disease-free survival (DFS) of allografted patients was 8.2 months. The 34 other CR patients were scheduled for autologous peripheral blood (PB) SCT (intent-to-treat group). Actually, autologous transplantation was only carried out in 22 patients (65%) (17 PBSCT and five autologous bone marrow transplantation (BMT)). Reasons for not autografting were early relapse (three patients), severe toxicity of EMA chemotherapy (six patients), and refusal or failure of stem cell harvest (three patients). The 3-year DFS rate of patients actually autografted was 77%. Among the 17 autografted patients still in CR2, nine patients have already reached a longer CR2 than first CR (CR1). Results of detection of PML/RARalpha by RT-PCR after autologous transplantation show negative findings in eight of the nine patients tested. We conclude that (1) ATRA combined to EMA chemotherapy is effective in the treatment of relapsed APL; (2) allogeneic BMT may be too toxic after salvage treatment including EMA intensive chemotherapy; (3) clinical outcome of autografted patients and preliminary molecular results regarding detection of PML/RARalpha after autologous PBSCT are encouraging. -------------------------------------------------------------------------------- Bone Marrow Transplant 1999 Aug;24(3):345-8 Arsenic and all-trans retinoic acid as induction therapy before autograft in a case of relapsed resistant secondary acute promyelocytic leukemia. Galimberti S, Papineschi F, Carmignani A, Testi R, Fazzi R, Petrini M. Oncology Department, University of Pisa, Italy. Arsenic trioxide has recently been reported to be successful in the treatment of promyelocytic leukemia. Several concerns about the use of this toxic agent are currently reducing its potential clinical use even in severely ill patients. In this report we describe the results achieved by As2O3 with all-trans retinoic acid in a patient suffering from secondary, relapsed, resistant promyelocytic leukemia. Several complications, including sepsis and an extensive area of skin necrosis, did not allow us to treat the patient further with chemotherapy. With As2O3 and ATRA therapy, the patient obtained a complete molecular remission without any significant toxicity and, subsequently, it was possible to perform a bone marrow autograft in a state of complete remission