The VEXAS syndrome, a genetically defined autoimmune disease, associated with various hematological neoplasms has been attracting growing attention since its initial description in 2020. While various therapeutic strategies have been explored in case studies, the optimal treatment strategy is still under investigation and allogeneic cell transplantation is considered the only curative treatment. Here, we describe 2 patients who achieved complete molecular remission of the underlying UBA1 mutant clone outside the context of allogeneic HCT. Both patients received treatment with the hypomethylating agent azacitidine, and deep molecular remission triggered treatment de-escalation and even cessation with sustained molecular remission in one of them. Prospective studies are necessary to clarify which VEXAS patients will benefit most from hypomethylating therapy and to understand the variability in the response to different treatment strategies.

Giant cell arteritis and Takayasu arteritis are two types of primary large-vessel vasculitis (LVV). Although glucocorticoids (GC) are the standard treatment for LVV, the disease relapse rates are high. Recent clinical trials on biological disease-modifying anti-rheumatic drugs (bDMARDs) and Janus kinase (JAK) inhibitors have demonstrated their efficacy in reducing LVV relapse rates and GC dosages. However, the control of residual inflammation and degenerative alterations in the vessel wall remains an outstanding requirement in the clinical management of LVV. The analysis of immune cell phenotypes in patients with LVV may predict their response to treatment with bDMARDs and JAK inhibitors and guide their optimal use. In this mini-review, we focused on molecular markers, including the immune cell proportions and gene expression, in patients with LVV and in mouse models of LVV treated with bDMARDs and JAK inhibitors.

Acute myeloid leukemia (AML) is an aggressive, heterogeneous group of malignancies with different clinical behaviors and different responses to therapy. For many types of cancer, finding cancer early makes it easier to treat. Identifying prognostic molecular markers and understanding their biology are the first steps toward developing novel diagnostic tools or therapies for patients with AML. In this study, we defined proteins and genes that can be used in the prognosis of different acute leukemia cases and found possible uses in diagnostics and therapy. We analyzed newly diagnosed acute leukemia cases positive for t (15; 17) (q22; q21) PML-RAR alpha, acute promyelocytic leukemia (APL). The samples of bone marrow cells were collected from patients at the diagnosis stage, as follow-up samples during standard treatment with all-trans retinoic acid, idarubicin, and mitoxantrone, and at the molecular remission. We determined changes in the expression of genes involved in leukemia cell growth, apoptosis, and differentiation. We observed that WT1, CALR, CAV1, and MYC genes\' expression in all APL patients with no relapse history was downregulated after treatment and could be potential markers associated with the pathology, thereby revealing the potential value of this approach for a better characterization of the prediction of APL outcomes.

The overall survival of Acute Promyelocytic Leukemia (APL), reported in recent studies, is approaching to 90% wherein, arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are used as the mainstay of treatment with either limited or no use of anthracycline and cytarabine. This study is aimed to ascertain the outcome of children with APL using similar approach. A total of 30 patients with APL, registered from January 2015 to December 2018, were reviewed. Diagnosis was established on bone marrow aspirate and confirmed by the presence of PML-RARA translocation. Treatment protocol was based on Australian APML 4 study performed by Australian Leukemia Lymphoma Group (ALLG). Lumbar puncture was not performed as it was not part of the protocol due to the risk of bleeding. The mean age in current cohort was 9 years with 53% males. Seven (23.3%) patients died and three (10%) abandoned treatment during induction. Twenty patients completed the intensive phase of chemotherapy and all (100%) of them attained molecular remission (MR). One patient dropped out after MR whereas, 19 remain on follow up with no evidence of disease, reflecting disease free survival (DFS) of 95%. With a median follow up of 2.5 years (range 2.1-4.8 years) the 5 years Kaplan-Meier estimate of OS was 63% and 73%, with and without abandonment, respectively. Analysis of outcome according to risk groups revealed inferior outcome of high risk (HR) group (38% and 50% with and without abandonment, respectively) in contrast to standard risk (SR) group which showed better outcome (82% and 88% with and without abandonment, respectively). The attainment of 100% molecular remission and absence of relapse supports the effectiveness of this regimen. Moreover, it is found to be less toxic and therefore, can be conveniently managed in day-care settings.

In patients with acute lymphoblastic leukemia (ALL) the risk of recurrent leukemia influences the choice of treatment between chemotherapy and allogeneic hematopoietic cell transplantation. The evaluation of minimal residual disease (MRD) is now considered to be the greatest progress in risk stratification in regard to leukemia recurrence. Achieving molecular remission at the end of induction therapy after diagnosis or after relapse has influenced treatment choice. Failure to achieve molecular remission is considered \"high risk\" and allogeneic hematopoietic cell transplantation with a suitable donor, the accepted standard. Nevertheless, published reports support lower relapse and higher survival rates for those in molecular remission at transplantation compared to those in morphological remission. In the setting of relapsed ALL, the availability of targeted therapies offers an opportunity for molecular remission so that transplant recipients have the best possible option of attaining sustained remission upon completion of this treatment.

APML is a highly curable hematological malignancy which is treated with differentiation agents and chemotherapy. The morbidity caused by chemotherapy in the treatment of APML is a great cause of concern. We treated 12 patients with newly diagnosed APML with single agent arsenic trioxide between 2010 and 2014 irrespective of risk stratification. Out of 12 patient 2 patients died during induction. All the ten patients who completed induction, completed their consolidation and maintenance without any delays. One out of these ten patients relapsed 10 months after treatment. The remaining nine patients (80 %) are in molecular remission and are under regular follow up. The toxicity with arsenic was negligible and was very well tolerated. Hence arsenic trioxide as single agent can be offered as a standard alternative regimen to ATRA based chemotherapy in patients with economic constraints.

After 25 years, evaluation of minimal residual disease (MRD) in follicular lymphoma (FL) has become a standardized technique frequently integrated into clinical trials for its consistent and independent prognostic significance. Achievement of a sustained MRD negativity is a marker of treatment sensibility that has been associated with excellent clinical outcome in terms of clinical response and progression-free survival, independently from the employed therapy. However, no survival advantages has been reported for MRD negative patients and despite the compelling results of clinical trials, MRD evaluation has currently no role in clinical practice. Ongoing clinical trials will help in clarifying the potential setting in which MRD monitoring may have a routine clinical application i.e. allowing de-escalation of standard maintenance therapy in very low risk patients. In this review the clinical implications of MRD monitoring in Rituximab-era are discussed in light of the current treatment paradigms most aimed at reducing toxicities, and the response definition that now routinely integrates PET scan.

Autologous stem cell transplantation (ASCT) for adult acute myelogenous leukemia (AML) is a valid therapeutic option for patients with good-risk and intermediate-risk disease. The authors used the registry of the European Society for Blood and Marrow Transplantation to compare combined busulfan and melphalan (BUMEL) with combined busulfan and cyclophosphamide (BUCY) before transplantation.
From 2005 to 2013, 853 patients with available cytogenetics underwent ASCT in first remission, including 257 after receiving BUMEL and 596 after receiving BUCY. The proportion of patients with good-risk AML was lower in those who received BUMEL (14% vs 20%; P = .02). More patients who received BUMEL underwent autograft in molecular remission (89% vs 78%; P = .02). Three years after transplantation, the relapse incidence (RI) was 48.7%, the leukemia-free survival (LFS) rate was 47.7%, the overall survival (OS) rate was 66.2%, and the nonrelapse mortality (NRM) rate was 3.6%.
Patients who underwent an autograft after receiving BUMEL fared better than those who underwent an autograft after receiving BUCY with a lower RI (39.5% vs 52.2%; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.49-0.87; P = .003) a better LFS (55.4% vs 44.6%; HR, 0.69; 95% CI, 0.53-0.89; P = .005), and a better OS (73.8% vs 63%; HR, 0.62; 95% CI, 0.47-0.82; P = .0007). There was no difference in the NRM rate (BUMEL vs BUCY, 4.5% vs 3.2%, respectively). Among 74 patients in the BUMEL group and 187 in the BUCY group who underwent autograft in molecular remission, the RI was 30% versus 51%, respectively (univariate analysis; P = .01), and the LFS rate was 66% versus 47%, respectively (univariate analysis; P = .03).
In patients with AML in first complete remission who undergo ASCT, the BUMEL combination is a better preparative regimen. Cancer 2017;123:824-31. © 2016 American Cancer Society.

BCR-ABL1 tyrosine kinase inhibitors (TKIs) have dramatically transformed the treatment of patients with chronic myelogenous leukemia (CML). Given the impressive and sustained response to TKI therapy that the majority of treated patients with CML enjoy, recent studies have explored the potential to achieve treatment-free remission in select patients, which may allow these patients to escape the adverse clinical and financial effects associated with life-long TKI therapy. The results of multiple prospective trials have demonstrated that patients who maintain a deep molecular response for at least 2 years with TKI treatment may be eligible for trial of TKI discontinuation. Mounting data indicates that approximately 40% of those who discontinue therapy on trial will remain in remission at least 1 year after TKI discontinuation; the majority of patients with molecular recurrence relapse within the first 6 months after TKI discontinuation, and TKI retreatment is highly effective in restoring response. Sokol score, duration of TKI therapy, depth of molecular response, and the presence of natural killer cells may all be associated with a higher probability of attaining treatment-free remission. Moving forward, emerging data from ongoing TKI discontinuation trials will allow for appropriate selection of patients with CML eligible for this approach, will expand our current understanding of the CML stem cell, and identify therapeutic interventions capable of effectively deleting the malignant hematopoietic stem cell.

The prognosis of acute promyelocytic leukemia (APL) has become the most favorable among all acute myeloid leukemias, due to the efficacy of treatment with all-trans retinoic acid (ATRA). ATRA combined with anthracycline-based chemotherapy has significantly improved the long-term outcome for low-to-intermediate-risk APL patients; thus, the efficacy of maintenance therapy for patients achieving molecular complete remission (MCR) following consolidation therapy has become debatable. To evaluate the efficacy of maintenance therapy, we conducted a retrospective analysis of 11 consecutive patients with low-to-intermediate-risk APL who received induction and consolidation therapy with ATRA and anthracyclines according to the PETHEMA LPA protocols at our hospital between January, 2001 and March, 2013. All the patients achieved MCR following consolidation therapy. Of these patients, 7 were followed without maintenance therapy, including 2 patients who discontinued maintenance therapy within 2 months. With a median follow-up of 85 months, the overall survival for all the patients was 100%, while the disease-free survival estimate at 5 years with and without maintenance therapy was 100 and 85.7%, respectively; the difference was not statistically significant (P=0.45). Two patients treated with maintenance therapy later developed secondary primary malignancy. Thus, even without maintenance therapy, ATRA combined with anthracyclines exhibited significant efficacy in low-to-intermediate-risk APL patients, suggesting that maintenance therapy, which is associated with adverse events, may be dispensable for patients achieving MCR following adequate consolidation therapy.