The role of ponatinib in adult BCR-ABL1 positive acute lymphoblastic leukemia after allogeneic transplantation: a real-life retrospective multicenter study.

The experience of third-generation tyrosine kinase inhibitor ponatinib treatment in Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph'+ ALL) patients post-allogeneic transplantation is limited. We retrospectively collected data on 25 Ph'+ ALL patients who were started on ponatinib after allogeneic transplantation between July 2015 and July 2019 from nine transplantation centers in Italy. Ponatinib was given in prophylaxis in five (20%), as pre-emptive treatment in seven (28%), and as salvage therapy in thirteen (52%) patients. It was combined with donor leukocyte infusions in ten patients. Half of the patients (12/25) harbored T315I mutation of BCR/ABL1, while in the remaining mutational analysis was negative or not performed. Among the 20 patients who received ponatinib as pre-emptive/salvage treatment, complete molecular response was achieved in 15 (75%) patients. Estimated overall survival at 2-year post-initiation of treatment in the whole cohort was 65% (respectively 60%, 60%, and 78% for the prophylaxis, pre-emptive, and salvage therapy groups). In patients with T315I-positive mutational status, the estimated 2-year survival was 40%. Fourteen patients (56%) experienced toxicity, requiring temporary or definitive suspension of treatment. In conclusion, treatment of Ph'+ ALL patients with ponatinib after transplantation is effective, although the question of adequate drug dose and treatment duration remains unanswered.

Pomalidomide-Responsive Extramedullary Myeloma Relapsed after Allogeneic Hematopoietic Transplant and Refractory to Multiple Lines of Chemotherapy.

Patients who experience extramedullary relapses (EMR) of multiple myeloma (MM) have an adverse prognosis, also in this era of novel agents like proteasome inhibitors and immunomodulatory drugs. We describe the case of an MM patient with EMR at 2 different sites after allogeneic stem cell transplantation. EMR was refractory to bortezomib, anthracycline, and bendamustine, but the patient achieved long-term complete remission (4 years) with pomalidomide and dexamethasone. This supports the hypothesis that this could be due to the graft-versus-myeloma effect during therapy enhanced by pomalidomide.

B-ALL Relapses After Autologous Stem Cell Transplantation Associated With a Shift from e1a2 to e14a2 BCR-ABL Transcripts: A Case Report.

BACKGROUND/AIM: The Philadelphia chromosome is found in 30% of acute lymphoblastic leukemia (ALL) patients, a distinct ALL subgroup where the BCR-ABL fusion gene is associated with poor prognosis. Treatment with tyrosine kinase inhibitors (TKIs) often induces complete remission and these patients subsequently undergo an autologous stem cell transplantation (ASCT). However, 20% of subjects experience a relapse associated with the selection of point-mutations in the BCR-ABL kinase domain. We report the clinical evolution of a Philadelphia-positive ALL patient co-expressing the e1a2 and e14a2 BCR-ABL transcript at diagnosis. MATERIALS AND METHODS: Multiplex reverse transcriptase (RT)-PCR was used to detect BCR-ABL transcripts and their levels were measured by quantitative Real Time PCR. Clonal sequencing and next-generation sequencing (NGS) were used to identify mutations. RESULTS: Although the patient underwent ASCT following treatment with multiple TKIs, he relapsed twice. The first time he exhibited the e1a2 transcript and the second time he presented only the e14a2 variant. Mutation analysis, performed by clonal sequencing and NGS, detected two alterations after the first relapse and a single mutation at the time of the second relapse. CONCLUSION: The observed shift from the e1a2 to the e14a2 variant and the selection of TKI-resistant clones heavily contributed to the fatal evolution of the disease.

Long-Term Molecular Remission Achieved by Antibody Anti-CD22 and Ponatinib in a Patient Affected by Ph'+ Acute Lymphoblastic Leukemia Relapsed after Second Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report.

Ph'+ acute lymphoblastic leukemia (Ph'+-ALL) is an oncohematologic disorder for which allogeneic bone marrow transplantation still offers the only chance of cure. However, relapse is the main reason for treatment failure, also after hematopoietic stem cell transplantation (HSCT). New drugs, such as third generation tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have expanded the therapeutic landscape, especially in patients who relapsed before HSCT. Very few reports, up to now, have described the use of both classes of these new agents in combination with donor lymphocyte infusions (DLI) in the setting of patients who relapsed after HSCT. We report on a young patient affected by Ph'+-ALL, who relapsed after the second HSCT and who reached molecular remission and long-term disease control by treatment with the anti-CD22 monoclonal antibody inotuzumab ozogamicin, DLI, and the 3rd generation TKI ponatinib.

Gels from a semifluorinated n-alkane in fluorinated solvents as a probe for intermolecular interactions.

Diblock semifluorinated n-alkanes can form aggregates and gels in fluorinated solvents. We have investigated the thermal behavior of binary mixtures comprising F(CF(2))(8)(CH(2))(16)H and fluorinated solvents. The solvents were perfluorohexane, perfluoroheptane, perfluorooctane, perfluorooctyl bromide, perfluorodecalin, and perfluorotributylamine. The phase diagrams were used to calculate the activity coefficients of the two components and the main excess thermodynamic functions. The solubility and self-assembly behavior of F(8)H(16) in the fluorinated solvents are related to the different solute-solvent dispersion interactions that depend on the polarizabilities and ionization potentials of the interacting species, and on the structural properties of the solvent.

Analysis of kavalactones from Piper methysticum (kava-kava).

The chemical analysis and quality control of both Piper methysticum G. Forster (kava-kava) and extracts obtained by aqueous acetone or aqueous methanol as well as supercritical fluid extraction are reviewed. In the last two decades various procedures concerning the separation and detection of kavalactones have been routinely carried out by gas chromatography (without previous derivatization of kavalactones) and high performance liquid chromatography but most of them are not validated or only partially validated. Recently, analyses by supercritical fluid chromatography and micellar electrokinetic chromatography have also been reported. Both gas chromatography and high performance liquid chromatography can be used for the analysis of kavalactones with some advantages and disadvantages for each method. Using gas chromatography analysis, methysticin and yangonin, which are two of the major components, are generally not separated. In addition, the high temperature of the injection port caused the decomposition of methysticin. Concerning high performance liquid chromatography analyses, the reversed-phase is generally better because highly reproducible with a very low detection limit for all compounds even if the quantitative analysis of the kavalactones by liquid chromatography needs to be carried out in the absence of light to prevent the cis/trans isomerisation of yangonin.