Impact of allogeneic stem cell transplantation on survival of patients less than 65 years of age with primary myelofibrosis

Kröger, Nicolaus; Giorgino, Toni; Scott, Bart L.; Ditschkowski, Markus; Alchalby, Haefaa; Cervantes, Francisco; Vannucchi, Alessandro M.; Cazzola, Mario; Morra, Enrica; Zabelina, Tatjana; Maffioli, Margherita; Pereira, Arturo; Beelen, Dietrich; Deeg, H. Joachim; Passamonti, Francesco

doi:10.1182/blood-2014-10-608315

Cited by 156 publications

(113 citation statements)

References 17 publications

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“…The current paucity of disease-modifying drugs in MF reinforces the early consideration of ASCT in DIPSS-plus high or intermediate 2 risk or molecularly high risk disease [152]. The introduction of nextgeneration sequencing in routine clinical practice provides the opportunity to genetically refine current prognostic models in MF.…”

Section: The Futurementioning

confidence: 99%

Myeloproliferative neoplasms: A decade of discoveries and treatment advances

2015

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Myeloproliferative neoplasms (MPN) are clonal stem cell diseases, first conceptualized in 1951 by William Dameshek, and historically included chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). In 1960, Nowell and Hungerford discovered an invariable association between the Philadelphia chromosome (subsequently shown to harbor the causal BCR‐ABL1 mutation) and CML; accordingly, the term MPN is primarily reserved for PV, ET, and PMF, although it includes other related clinicopathologic entities, according to the World Health Organization (WHO) classification system. In 2005, William Vainchenker and others described a Janus kinase 2 mutation (JAK2V617F) in MPN and this was followed by a series of additional descriptions of mutations that directly or indirectly activate JAK‐STAT: JAK2 exon 12, myeloproliferative leukemia virus oncogene (MPL) and calreticulin (CALR) mutations. The discovery of these, mostly mutually exclusive, “driver” mutations has contributed to revisions of the WHO diagnostic criteria and risk stratification in MPN. Mutations other than JAK2, CALR and MPL have also been described in MPN and shown to provide additional prognostic information. From the standpoint of treatment, over the last 50 years, Louis Wasserman from the Unites States and Tiziano Barbui from Italy had skillfully organized and led a number of important clinical trials, whose results form the basis for current treatment strategies in MPN. More recently, allogeneic stem cell transplant, as a potentially curative treatment modality, and JAK inhibitors, as palliative drugs, have been added to the overall therapeutic armamentarium in myelofibrosis. In the current review, I will summarize the important advances made in the last 10 years regarding the science and practice of MPN. Am. J. Hematol. 91:50–58, 2016. © 2015 Wiley Periodicals, Inc.

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Section: The Futurementioning

confidence: 99%

Myeloproliferative neoplasms: A decade of discoveries and treatment advances

2015

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“…97 Allogeneic hematopoietic cell transplantation (allo-HCT), still the only treatment modality with curative potential, should be offered to all patients with higher-risk MF. 157,158 Although the timing of allo-HCT in patients receiving ruxolitinib is not known with certainty, retrospective studies suggest that prior ruxolitinib therapy does not compromise allo-HCT outcomes and that the drug should be continued almost up until the time of conditioning. 159 A plethora of other targeted agents are being studied in MPNs, mostly in MF, both alone and in combination with ruxolitinib.…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

JAK2 inhibitors for myeloproliferative neoplasms: what is next?

Bose

Verstovšek

2017

Blood

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Since its approval in 2011, the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib has evolved to become the centerpiece of therapy for myelofibrosis (MF), and its use in patients with hydroxyurea resistant or intolerant polycythemia vera (PV) is steadily increasing. Several other JAK2 inhibitors have entered clinical testing, but none have been approved and many have been discontinued. Importantly, the activity of these agents is not restricted to patients with JAK2 V617F or exon 12 mutations. Although JAK2 inhibitors provide substantial clinical benefit, their disease-modifying activity is limited, and rational combinations with other targeted agents are needed, particularly in MF, in which survival is short. Many such combinations are being explored, as are other novel agents, some of which could successfully be combined with JAK2 inhibitors in the future. In addition, new JAK2 inhibitors with the potential for less myelosuppression continue to be investigated. Given the proven safety and efficacy of ruxolitinib, it is likely that ruxolitinib-based combinations will be a major way forward in drug development for MF. If approved, less myelosuppressive JAK2 inhibitors such as pacritinib or NS-018 could prove to be very useful additions to the therapeutic armamentarium in MF. In PV, inhibitors of histone deacetylases and human double minute 2 have activity, but their role, if any, in the future treatment algorithm is uncertain, given the availability of ruxolitinib and renewed interest in interferons. Ruxolitinib is in late-phase clinical trials in essential thrombocythemia, in which it could fill an important void for patients with troublesome symptoms.

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“…Az allo-HSCT jelenti az egyetlen potenciálisan kuratív megoldást, de szem előtt kell tartani a beavatkozáshoz köthető jelentős mortalitást is, így valójában elsősorban azoknak ajánlha-tó, akiknél a várható túlélés nem éri el az 5 évet és a leukaemiás transzformáció kockázata meghaladja a 20%-ot. A DIPSS-plusz besorolást és a hagyományos (JAK2-inhibitor előtti) kezelési módokat figyelembe véve, egy kö-zel 500 beteget vizsgáló tanulmány alapján elmondható, hogy egyértelmű túlélésbeli előnyt az allo-HSCT elvég-zése csak az intermedier-2 vagy nagy rizikójú betegek számára hozott [34] (III/A evidencia). Az allo-HSCTre való alkalmasság meghatározására egyértelmű konszenzus nincs, a felső korhatár 60 (65-70) év.…”

Section: Dipss-plusz éRték Szerint Nagy Vagy Intermedier-2 Rizikó (Vaunclassified

Aktualitások a primer myelofibrosis ellátásában

et al. 2016

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A primer myelofibrosis a Philadelphia-negatív krónikus myeloid neoplasiák közé tartozó ritka kórkép, amelyre jellemző a cytopeniák és hepatosplenomegalia kialakulása. A betegség etiológiája ugyan jelenleg sem ismert, de az utóbbi 10 -és még inkább a legutóbbi három -évben a patogenezisét és prognózisát tekintve ismereteink jelentősen bővül-tek. 2015-ben Magyarországon is elérhetővé vált a JAK2-gátló ruxolitinib a betegség kezelésére, amely a splenomegalia mérséklésén és a betegséghez társuló tünetek javításán túl a túlélési eredményeket is javíthatja. A primer myelofibrosis ellátásában tehát egyfajta szemléletváltás bontakozott ki, amely miatt időszerű a betegséggel kapcsolatos ismeretek összefoglalása. Orv. Hetil., 2016, 157(39), 1547-1556. Kulcsszavak: Philadelphia-negatív myeloproliferativ betegség, myelofibrosis, WHO 2016, calreticulin, JAK2, ruxolitinib Actualities in the management of primary myelofibrosisPrimary myelofibrosis is one of the Philadelphia negative chronic myeloproliferative neoplasms. It is a rare disease featured by cytopenias and hepatosplenomegaly. Although the etiology of the disease is still unknown, our knowledge about its pathology and prognosis has been improving in the last few years. Furthermore, the JAK2 inhibitor ruxolitinib has become available in Hungary since 2015. Beside its high efficacy in spleen volume and in reduction of myelofibrosis-associated symptoms, this novel therapy also exerts a disease-modifying effect and, therefore, ruxolitinib may improve the life expectancy too. Treatment approach of myelofibrosis has been changed these years, which gives a reason for this summary. Keywords: Philadelphia negative myeloproliferative neoplasms, myelofibrosis, WHO 2016, calreticulin, JAK2, ruxolitinibSimon, Zs., Marton, I., Borbényi, Z., Illés, Á. [Actualities in the management of primary myelofibrosis]. Orv. Hetil., 2016, 157(39), 1547-1556.

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Impact of allogeneic stem cell transplantation on survival of patients less than 65 years of age with primary myelofibrosis

Abstract: Key Points Transplant vs nontransplant approaches were compared in PMF patients grouped by DIPSS status. The net benefit of transplant vs nontransplant is marked in higher-risk patients.

Cited by 156 publications

References 17 publications

Myeloproliferative neoplasms: A decade of discoveries and treatment advances

Myeloproliferative neoplasms: A decade of discoveries and treatment advances

JAK2 inhibitors for myeloproliferative neoplasms: what is next?

Aktualitások a primer myelofibrosis ellátásában

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