nach oben

Erschienen in:

01.06.2015 | Original Article

Allogeneic transplantation with myeloablative FluBu4 conditioning improves survival compared to reduced intensity FluBu2 conditioning for acute myeloid leukemia in remission

verfasst von: John M. Magenau, Thomas Braun, Pavan Reddy, Brian Parkin, Attaphol Pawarode, Shin Mineishi, Sung Choi, John Levine, Yumeng Li, Gregory Yanik, Carrie Kitko, Tracey Churay, David Frame, Mary Mansour Riwes, Andrew Harris, Dale Bixby, Daniel R. Couriel, Steven C. Goldstein

Erschienen in: Annals of Hematology | Ausgabe 6/2015

Einloggen, um Zugang zu erhalten

Abstract

The optimal intensity of conditioning for allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) remains undefined. Traditionally, myeloablative conditioning regimens improve disease control, but at the risk of greater nonrelapse mortality. Because fludarabine with myeloablative doses of intravenous busulfan using pharmacokinetic monitoring has excellent tolerability, we reasoned that this regimen would limit relapse without substantially elevating toxicity when compared to reduced intensity conditioning. We retrospectively analyzed 148 consecutive AML patients in remission receiving T cell replete HCT conditioned with fludarabine and intravenous busulfan at doses defined as reduced (6.4 mg/kg; FluBu2, n = 63) or myeloablative (12.8 mg/kg; FluBu4, n = 85). Early and late nonrelapse mortality (NRM) was similar among FluBu4 and FluBu2 recipients, respectively (day + 100: 4 vs 0 %; 5 years: 19 vs 22 %; p = 0.54). NRM did not differ between FluBu4 and FluBu2 in patients >50 years of age (24 vs 22 %, p = 0.75). Relapse was lower in recipients of FluBu4 (5 years: 30 vs 49 %; p = 0.04), especially in patients with poor risk cytogenetics (22 vs 59 %; p = 0.02) and those >50 years of age (28 vs 51 %; p = 0.02). Overall survival favored FluBu4 recipients at 5 years (53 vs 34 %, p = 0.02), a finding confirmed in multivariate analysis (HR: 0.57; 95 % CI: 0.34–0.95; p = 0.03). These data suggest that myeloablative FluBu4 may provide equivalent NRM, reduced relapse, and improved survival compared to FluBu2, emphasizing the importance of busulfan dose in conditioning for AML.

Rowe JM (2009) Optimal induction and post-remission therapy for AML in first remission. Hematol Am Soc Hematol Educ Program 396-405. doi:10.1182/asheducation-2009.1.396

Stone RM (2013) Acute myeloid leukemia in first remission: to choose transplantation or not? J Clin Oncol 31(10):1262–1266CrossRefPubMed

Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P, O’Brien S, Khouri I, Gajewski J, Mehra R, Claxton D, Andersson B, Beran M, Przepiorka D, Koller C, Kornblau S, Korbling M, Keating M, Kantarjian H, Champlin R (1997) Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 89(12):4531–4536PubMed

Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, Varadi G, Kirschbaum M, Ackerstein A, Samuel S, Amar A, Brautbar C, Ben-Tal O, Eldor A, Or R (1998) Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 91(3):756–763PubMed

Niederwieser D, Maris M, Shizuru JA, Petersdorf E, Hegenbart U, Sandmaier BM, Maloney DG, Storer B, Lange T, Chauncey T, Deininger M, Ponisch W, Anasetti C, Woolfrey A, Little MT, Blume KG, McSweeney PA, Storb RF (2003) Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood 101(4):1620–1629CrossRefPubMed

Storb RF, Champlin R, Riddell SR, Murata M, Bryant S, Warren EH (2001) Non-myeloablative transplants for malignant disease. Hematol Am Soc Hematol Educ Program 375-391

Luger SM, Ringden O, Zhang MJ, Perez WS, Bishop MR, Bornhauser M, Bredeson CN, Cairo MS, Copelan EA, Gale RP, Giralt SA, Gulbas Z, Gupta V, Hale GA, Lazarus HM, Lewis VA, Lill MC, McCarthy PL, Weisdorf DJ, Pulsipher MA (2012) Similar outcomes using myeloablative vs reduced-intensity allogeneic transplant preparative regimens for AML or MDS. Bone Marrow Transplant 47(2):203–211CrossRefPubMedCentralPubMed

Aoudjhane M, Labopin M, Gorin NC, Shimoni A, Ruutu T, Kolb HJ, Frassoni F, Boiron JM, Yin JL, Finke J, Shouten H, Blaise D, Falda M, Fauser AA, Esteve J, Polge E, Slavin S, Niederwieser D, Nagler A, Rocha V, Acute Leukemia Working Party of the European Group for B, Marrow T (2005) Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT). Leukemia 19(12):2304–2312CrossRefPubMed

Ringden O, Labopin M, Ehninger G, Niederwieser D, Olsson R, Basara N, Finke J, Schwerdtfeger R, Eder M, Bunjes D, Gorin NC, Mohty M, Rocha V (2009) Reduced intensity conditioning compared with myeloablative conditioning using unrelated donor transplants in patients with acute myeloid leukemia. J Clin Oncol 27(27):4570–4577CrossRefPubMed

10.

Alyea EP, Kim HT, Ho V, Cutler C, DeAngelo DJ, Stone R, Ritz J, Antin JH, Soiffer RJ (2006) Impact of conditioning regimen intensity on outcome of allogeneic hematopoietic cell transplantation for advanced acute myelogenous leukemia and myelodysplastic syndrome. Biol Blood Marrow Transplant 12(10):1047–1055CrossRefPubMed

11.

Scott BL, Sandmaier BM, Storer B, Maris MB, Sorror ML, Maloney DG, Chauncey TR, Storb R, Deeg HJ (2006) Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis. Leukemia 20(1):128–135CrossRefPubMed

12.

de Lima M, Couriel D, Thall PF, Wang X, Madden T, Jones R, Shpall EJ, Shahjahan M, Pierre B, Giralt S, Korbling M, Russell JA, Champlin RE, Andersson BS (2004) Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood 104(3):857–864CrossRefPubMed

13.

Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, Sandmaier B (2009) Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant 15(3):367–369CrossRefPubMedCentralPubMed

14.

Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, Apperley J, Slavin S, Pasquini M, Sandmaier BM, Barrett J, Blaise D, Lowski R, Horowitz M (2009) Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant 15(12):1628–1633CrossRefPubMedCentralPubMed

15.

Shimoni A, Hardan I, Shem-Tov N, Yeshurun M, Yerushalmi R, Avigdor A, Ben-Bassat I, Nagler A (2006) Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensity. Leukemia 20(2):322–328CrossRefPubMed

16.

Shimoni A, Hardan I, Shem-Tov N, Yerushalmi R, Nagler A (2010) Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: long-term follow-up. Leukemia 24(5):1050–1052CrossRefPubMed

17.

Kharfan-Dabaja MA, Labopin M, Bazarbachi A, Hamladji RM, Blaise D, Socie G, Lioure B, Bermudez A, Lopez-Corral L, Or R, Arcese W, Fegueux N, Nagler A, Mohty M (2014) Comparing i.v. BU dose intensity between two regimens (FB2 vs FB4) for allogeneic HCT for AML in CR1: a report from the Acute Leukemia Working Party of EBMT. Bone Marrow Transplant 49(9):1170–1175CrossRefPubMed

18.

Copelan EA, Hamilton BK, Avalos B, Ahn KW, Bolwell BJ, Zhu X, Aljurf M, van Besien K, Bredeson C, Cahn JY, Costa LJ, de Lima M, Gale RP, Hale GA, Halter J, Hamadani M, Inamoto Y, Kamble RT, Litzow MR, Loren AW, Marks DI, Olavarria E, Roy V, Sabloff M, Savani BN, Seftel M, Schouten HC, Ustun C, Waller EK, Weisdorf DJ, Wirk B, Horowitz MM, Arora M, Szer J, Cortes J, Kalaycio ME, Maziarz RT, Saber W (2013) Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood 122(24):3863–3870CrossRefPubMedCentralPubMed

19.

Clift RA, Buckner CD, Appelbaum FR, Bearman SI, Petersen FB, Fisher LD, Anasetti C, Beatty P, Bensinger WI, Doney K et al (1990) Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens. Blood 76(9):1867–1871PubMed

20.

Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd (1994) Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med 331(14):896–903CrossRefPubMed

21.

Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS (2009) Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med 361(13):1249–1259CrossRefPubMed

22.

Lowenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Dohner H, Gratwohl A, Pabst T, Verhoef G, Dutch-Belgian Cooperative Trial Group for H-O, German AMLSG, Swiss Group for Clinical Cancer Research Collaborative G (2009) High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med 361(13):1235–1248CrossRefPubMed

23.

Pasquini MC WZ (2011) Current use and outcome of hematopoietic stem cell transplantation: CIBMTR Summary Slides. Available at: http://www.cibmtr.org

24.

Grimwade D, Walker H, Harrison G, Oliver F, Chatters S, Harrison CJ, Wheatley K, Burnett AK, Goldstone AH (2001) The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood 98(5):1312–1320CrossRefPubMed

25.

Leith CP, Kopecky KJ, Chen IM, Eijdems L, Slovak ML, McConnell TS, Head DR, Weick J, Grever MR, Appelbaum FR, Willman CL (1999) Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group Study. Blood 94(3):1086–1099PubMed

26.

Ciurea SO, Andersson BS (2009) Busulfan in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 15(5):523–536CrossRefPubMedCentralPubMed

27.

Bredeson CN, Zhang MJ, Agovi MA, Bacigalupo A, Bahlis NJ, Ballen K, Brown C, Chaudhry MA, Horowitz MM, Kurian S, Quinlan D, Muehlenbien CE, Russell JA, Savoie L, Rizzo JD, Stewart DA (2008) Outcomes following HSCT using fludarabine, busulfan, and thymoglobulin: a matched comparison to allogeneic transplants conditioned with busulfan and cyclophosphamide. Biol Blood Marrow Transplant 14(9):993–1003CrossRefPubMedCentralPubMed

28.

Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M, Roberson S, Giralt S, Pierre B, Russell JA, Shpall EJ, Jones RB, Champlin RE (2008) Once daily i.v. busulfan and fludarabine (i.v. Bu-Flu) compares favorably with i.v. busulfan and cyclophosphamide (i.v. BuCy2) as pretransplant conditioning therapy in AML/MDS. Biol Blood Marrow Transplant 14(6):672–684CrossRefPubMedCentralPubMed

29.

Kreyenberg H, Holle W, Mohrle S, Niethammer D, Bader P (2003) Quantitative analysis of chimerism after allogeneic stem cell transplantation by PCR amplification of microsatellite markers and capillary electrophoresis with fluorescence detection: the Tuebingen experience. Leukemia 17(1):237–240CrossRefPubMed

30.

Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, Paietta E, Willman CL, Head DR, Rowe JM, Forman SJ, Appelbaum FR (2000) Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 96(13):4075–4083PubMed

31.

Gray R (1988) A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 16:1141–1154CrossRef

32.

Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94(446):496–509CrossRef

33.

Sorror ML, Giralt S, Sandmaier BM, De Lima M, Shahjahan M, Maloney DG, Deeg HJ, Appelbaum FR, Storer B, Storb R (2007) Hematopoietic cell transplantation specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences. Blood 110(13):4606–4613CrossRefPubMedCentralPubMed

34.

Sorror M, Storer B, Sandmaier BM, Maloney DG, Chauncey TR, Langston A, Maziarz RT, Pulsipher M, McSweeney PA, Storb R (2008) Hematopoietic cell transplantation-comorbidity index and Karnofsky performance status are independent predictors of morbidity and mortality after allogeneic nonmyeloablative hematopoietic cell transplantation. Cancer 112(9):1992–2001. doi:10.1002/cncr.23375 CrossRefPubMed

35.

Guilfoyle R, Demers A, Bredeson C, Richardson E, Rubinger M, Szwajcer D, Seftel MD (2009) Performance status, but not the hematopoietic cell transplantation comorbidity index (HCT-CI), predicts mortality at a Canadian transplant center. Bone Marrow Transplant 43(2):133–139CrossRefPubMed

36.

Devillier R, Crocchiolo R, Etienne A, Prebet T, Charbonnier A, Furst S, El-Cheikh J, D’Incan E, Rey J, Faucher C, Blaise D, Vey N (2012) Outcome of relapse after allogeneic stem cell transplant in patients with acute myeloid leukemia. Leuk Lymphoma. doi:10.3109/10428194.2012.741230

37.

Bredeson C, LeRademacher J, Kato K, Dipersio JF, Agura E, Devine SM, Appelbaum FR, Tomblyn MR, Laport GG, Zhu X, McCarthy PL, Ho VT, Cooke KR, Armstrong E, Smith A, Rizzo JD, Burkart JM, Pasquini MC (2013) Prospective cohort study comparing intravenous busulfan to total body irradiation in hematopoietic cell transplantation. Blood 122(24):3871–3878CrossRefPubMedCentralPubMed

38.

Lee JH, Joo YD, Kim H, Ryoo HM, Kim MK, Lee GW, Lee WS, Park JH, Bae SH, Hyun MS, Kim DY, Kim SD, Min YJ, Lee KH (2013) Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine. J Clin Oncol 31(6):701–709CrossRefPubMed

39.

Rambaldi A, Grassi A, Micò M, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, al. e (2014) Randomized trial of busulfan with cyclophosphamide versus busulfan with fludarabine as preparative regimen to allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: a study from the Gruppo Italiano Trapianto Midollo Osseo (GITMO). Blood 124 (21). Abstract #727

40.

Ben Barouch S, Cohen O, Vidal L, Avivi I, Ram R (2014) Busulfan fludarabine vs. busulfan cyclophosphamide as a preparative regimen prior to allogeneic hematopoietic cell transplantation – systematic review and meta-analysis. Blood 124 (21):Abstract 3872

41.

Soiffer RJ, Lerademacher J, Ho V, Kan F, Artz A, Champlin RE, Devine S, Isola L, Lazarus HM, Marks DI, Porter DL, Waller EK, Horowitz MM, Eapen M (2011) Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Blood 117(25):6963–6970CrossRefPubMedCentralPubMed

42.

Bornhauser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schafer-Eckart K, Holler E, Kroger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M (2012) Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol 13(10):1035–1044CrossRefPubMed

43.

Chen YB, Coughlin E, Kennedy KF, Alyea EP, Armand P, Attar EC, Ballen KK, Cutler C, Dey BR, Koreth J, McAfee SL, Spitzer TR, Antin JH, Soiffer RJ, Ho VT (2013) Busulfan dose intensity and outcomes in reduced-intensity allogeneic peripheral blood stem cell transplantation for myelodysplastic syndrome or acute myeloid leukemia. Biol Blood Marrow Transplant

44.

Pasquini M, Le-Rademacher J, Kato K, Zhu X, McCarthy P, Ho V, Cooke K, Armstrong B, Smith A, Rizzo J, Burkart J, Bredeson C (2013) Comparison of myeloblative intravenous busulfan with cyclophosphamide (BuCy) or fludarabine (BuFlu) prior to haematopoietic cell transplantation (HCT) for myeloid malignancies. CBMTG (Abstract 0379):S61-62

45.

Alatrash G, de Lima M, Hamerschlak N, Pelosini M, Wang X, Xiao L, Kerbauy F, Chiattone A, Rondon G, Qazilbash MH, Giralt SA, de Padua SL, Hosing C, Kebriaei P, Zhang W, Nieto Y, Saliba RM, Champlin RE, Andersson BS (2011) Myeloablative reduced-toxicity i.v. busulfan-fludarabine and allogeneic hematopoietic stem cell transplant for patients with acute myeloid leukemia or myelodysplastic syndrome in the sixth through eighth decades of life. Biol Blood Marrow Transplant 17(10):1490–1496CrossRefPubMedCentralPubMed

46.

Patel JP, Gonen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, Van Vlierberghe P, Dolgalev I, Thomas S, Aminova O, Huberman K, Cheng J, Viale A, Socci ND, Heguy A, Cherry A, Vance G, Higgins RR, Ketterling RP, Gallagher RE, Litzow M, van den Brink MR, Lazarus HM, Rowe JM, Luger S, Ferrando A, Paietta E, Tallman MS, Melnick A, Abdel-Wahab O, Levine RL (2012) Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 366(12):1079–1089CrossRefPubMedCentralPubMed

47.

ClinicalTrials.gov (Accessed 07/21/14) http://clinicaltrials.gov/show/NCT01339910. http://clinicaltrials.gov/show/NCT01339910.

48.

Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb HJ (2005) Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 23(24):5675–5687CrossRefPubMed

Titel: Allogeneic transplantation with myeloablative FluBu4 conditioning improves survival compared to reduced intensity FluBu2 conditioning for acute myeloid leukemia in remission
verfasst von: John M. Magenau
Thomas Braun
Pavan Reddy
Brian Parkin
Attaphol Pawarode
Shin Mineishi
Sung Choi
John Levine
Yumeng Li
Gregory Yanik
Carrie Kitko
Tracey Churay
David Frame
Mary Mansour Riwes
Andrew Harris
Dale Bixby
Daniel R. Couriel
Steven C. Goldstein
Publikationsdatum: 01.06.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 6/2015
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-015-2349-4

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

25.04.2024 | Hypotonie | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Allogeneic transplantation with myeloablative FluBu4 conditioning improves survival compared to reduced intensity FluBu2 conditioning for acute myeloid leukemia in remission

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Update Innere Medizin

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2015

A multi-state model approach for prediction in chronic myeloid leukaemia

Rituximab as frontline monotherapy in untreated hairy cell leukemia patients

Evaluation of bone marrow involvement in extranodal NK/T cell lymphoma by FDG-PET/CT

Modified ESHAP regimen for relapsed/refractory T cell lymphoma: a retrospective analysis

Cytomegalovirus retinitis complicating combination therapy with rituximab and fludarabine

First-line treatments for chronic lymphocytic leukaemia: interpreting efficacy data by network meta-analysis

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Update Innere Medizin