Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21)

Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8; 21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients with other subtypes of AML. However, similar to 40% of patients relapse, and the literature suggests that patients with inv(16) fare differently from those with t(8;21). We retrospectively analyzed 537 patients with CBF-AML, focusing on additional cytogenetic aberrations to examine their impact on clinical outcomes. Trisomies of chromosomes 8, 21, or 22 were significantly more common in patients with inv(16)/t(16;16): 16% vs 7%, 6% vs 0%, and 17% vs 0%, respectively. In contrast, del(9q) and loss of a sex chromosome were more frequent in patients with t(8;21): 15% vs 0.4% for del(9q), 37% vs 0% for loss of X in females, and 44% vs 5% for loss of Y in males. Hyperdiploidy was more frequent in patients with inv(16) (25% vs 9%, whereas hypodiploidy was more frequent in patients with t(8;21) (37% vs 3%. In multivariable analyses (adjusted for age, white blood counts at diagnosis, and KIT mutation status), trisomy 8 was associated with improved overall survival (OS) in inv(16), whereas the presence of other chromosomal abnormalities (not trisomy 8) was associated with decreased OS. In patients with t(8;21), hypodiploidy was associated with improved disease-free survival; hyperdiploidy and del(9q) were associated with improved OS. KIT mutation (either positive or not tested, compared with negative) conferred poor prognoses in univariate analysis only in patients with t(8;21)

Core-binding factor acute myeloid leukemia with t(8;21) Risk factors and a novel scoring system (I-CBFit)

Background: Although the prognosis of core-binding factor (CBF) acute myeloid leukemia (AML) is better than other subtypes of AML, 30% of patients still relapse and may require allogeneic hematopoietic cell transplantation (alloHCT). However, there is no validated widely accepted scoring system to predict patient subsets with higher risk of relapse. Methods: Eleven centers in the US and Europe evaluated 247 patients with t(8;21) (q22;q22). Results: Complete remission (CR) rate was high (92.7%), yet relapse occurred in 27.1% of patients. A total of 24.7% of patients received alloHCT. The median diseasefree (DFS) and overall (OS) survival were 20.8 and 31.2 months, respectively. Age, KIT D816V mutated (11.3%) or nontested (36.4%) compared with KIT D816V wild type (52.5%), high white blood cell counts (WBC), and pseudodiploidy compared with hyper- or hypodiploidy were included in a scoring system (named I-CBFit). DFS rate at 2 years was 76% for patients with a low-risk I-CBFit score compared with 36% for those with a high-risk I-CBFit score (P <0.0001). Low- vs high-risk OS at 2 years was 89% vs 51% (P <0.0001). Conclusions: I-CBFit composed of readily available risk factors can be useful to tailor the therapy of patients, especially for whom alloHCT is not need in CR1 (ie, patients with a low-risk score)

Structure and transport properties of the electronically correlated thiospinel CuV2S4

Diese Arbeit widmet sich der Einkristallzucht sowie der Charakterisierung der kristallografischen, magnetischen und insbesondere elektronischen Transporteigenschaften des metallischen Thiospinells CuV2S4, das eine enge Verwandschaft zum isostrukturellen und isoelektronischen LiV2O4 aufweist, dem einzigen bisher bekannten Schwere-Fermionen-System ohne f-Elektronen. Berichte über einen ebenfalls deutlich erhöhten Sommerfeldkoeffizient der spezifischen Wärme kennzeichnen auch CuV2S4 als elektronisch stark korreliertes System. Darüber hinaus durchläuft es bei 90 K einen Phasenübergang, der von der Ausbildung einer Ladungsdichtewelle (LDW) verursacht wird, deren Kommensurabilität sich nahe 75 K und 55 K nochmals abrupt ändert. Dieses typisch niedrigdimensionale Ordnungsphänomen ist ausgehend von einer kubischen Hochtemperaturphase äußerst ungewöhnlich und motivierte neben einer bislang ungeklärten Probenabhängigkeit, die mit der Wahl des Transportmittels (Chlor bzw. Iod) zu korrelieren schien, ebenfalls die in dieser Arbeit unternommenen Anstrengungen zur Zucht qualitativ hochwertiger Einkristalle mittels chemischen Gasphasentransports. Durch den direkten Vergleich von sowohl mit Iod bzw. Chlor als Transportmittel gewonnener Einkristalle gelang erstmals der signifikante Nachweis einer äußerst geringen Chlor-Kontamination als Ursache für die nahezu vollständige Unterdrückung der Phasenübergänge in den entsprechenden Einkristallen. Die starke Empfindlichkeit der LDW auf strukturelle Unordnung kommt auch in der enormen Steigerung des Restwiderstandsverhältnisses um mehr als eine Größenordnung zum Ausdruck, die durch eine geeignete Temperbehandlung nur in den mit Iod als Transportmittel gezüchteten Einkristallen erzielt werden konnte. Dadurch wurde erstmals auch die Signatur des dritten Phasenübergangs im elektrischen Widerstand sichtbar. Die nahezu identische Erhöhung der Übergangstemperaturen unter dem Einfluss externen hydrostatischen Drucks unterstreicht den gemeinsamen physikalischen Ursprung aller drei Phasenübergänge. Das unterhalb von 7 K beobachtbare T2-Verhalten im elektrischen Widerstand belegt neben anderen experimentellen Kenngrößen das Fermiflüssigkeitsverhalten der Leitungselektronen mit einer um eine Zehnerpotenz kleineren effektiven Masse als im LiV2O4 und erlaubt eine Interpretation im Rahmen eines Kondo-Szenarios.This work deals with the single crystal growth and the characterization of crystallographic, magnetic and mainly electronic transport properties of the metallic thiospinel CuV2S4, which is isostructural and isoelectronic to the heavy fermion system LiV2O4. Former reports of an enhanced Sommerfeld-coefficient of the specific heat indicated that electronic correlations are present in CuV2S4 as well. Additionally CuV2S4 shows a phase transition at 90 K, which has been associated with the formation of a charge density wave (CDW), whose propagation vector changes its length at two additional phase transitions close to 75 K and 55 K. The formation of a CDW is a typical low dimensional order phenomenon and very unusual for a three dimensional system with a cubic crystal symmetry in the high temperature phase. An additional motivation for the efforts to grow single crystals of this compound was a sample dependency which seemed to correlate with the type of transport agent (iodine or chlorine) used in the chemical transport reaction as the preferred preparation procedure for the single crystal growth. Due to the direct comparison of single crystals grown by both types of transport agents it could be shown that a very low concentration of chlorine is the origin for the almost complete suppression of the phase transitions in the corresponding type of single crystals. The strong sensitivity of the CDW-formation to disorder is also reflected by the huge increase of the residual resistivity ratio of more than one order of magnitude which could only be achieved by annealing procedures in the case of single crystals grown with iodine as transport agent. The high quality of the samples allowed for the first time to detect all three phase transition signatures in resistivity measurements. Their almost identical temperature dependence as a function of external hydrostatic pressure emphasizes their common physical origin. The coefficient of the T2 behavior of the electrical resistivity below 7 K confirms beside other experimental quantities the fermi liquid behavior of CuV2S4 with an effective mass which is one decade smaller than in LiV2O4 and allows an interpretation in the framework of a Kondo scenario