Acute myeloid leukemia (AML) is a hematological malignancy commonly found in adult patients. Low overall survival and resistance to therapy are the main issues in AML. The first line of treatment for AML chemotherapy is the induction phase, namely, the phase to induce remission by administering a combination of daunorubicin (DNR) for three days followed by administration of cytarabine (Ara-C) with continuous infusion for seven days, which is referred to as \"3 + 7.\" Such induction therapy has been the standard therapy for AML for the last four decades. This review article is made to discuss daunorubicin and cytarabine from their chemical structure, pharmacodynamics, pharmacokinetics, and mechanisms of resistance in AML.

BACKGROUND: Acute leukemia patients have a diminished survival inversely proportional to their age. 5-year overall survival in younger AML patients is 50%, however reduced to <10% if age >70. Factors contributing include poor performance status, decreased response to induction therapy, increased treatment related mortality, unfavorable cytogenetics and secondary leukemia.
OBJECTIVE: Report observed characteristics and outcomes of elderly leukemia patients.
METHODS: Retrospective chart review of newly diagnosed acute myeloid leukemia (AML) patients >65 admitted from 7/1/2015 through 6/30/2021. Demographic information, classification, duration of hospital stay, blood products administered, treatment, discharge condition, 3 and 6 month remission, and survival data collected.
METHODS: Academic medical center.
METHODS: 149 patients identified. AML[n=130], acute promyelocytic leukemia (APL)[n=9], and acute leukemia not otherwise specified (AML-NOS)[n=10].
METHODS: 97 patients treated. AML treatment: Induction therapy, daunorubicin and cytarabine (liposomal), or hypomethylating agent +/-venetoclax. APL treatment: all-trans retinoic acid (ATRA) +/- arsenic trioxide (ATO). One patient with AML-NOS received hypomethylator.
RESULTS: Patients separated into three groups: <70[n=55], 70 to 74[n=52], and >75[n=60]. Percent of patients who did not receive any therapy increased as age group increased (21.8%, 32.7%, and 41.7%). Length of hospital stay, reflective of treatment, was greatest in the younger population (28 days, 17.6 days, and 15.3 days). 6-month survival 51% younger, 42.3% middle and 23.4% for eldest cohort. Treatment related mortality (TRM) including transitioning to hospice care increased as age increased (29%, 34% and 50%).
RESULTS: 25/130 patients received induction chemotherapy. Nineteen patients were <70. The expected TRM for the younger cohort was 10.68% (1 - 41%) and 10.1% (1-20%) for elder cohort. The observed TRM was 10.5% in the younger cohort and 50% in the older cohort. Most of the eldest AML patients received a hypomethylating mono- or combination therapy. Nearly 50% of all AML were discharged home. The 6-month survival was 50% for younger, 26.8% for middle and 13.3% for eldest cohort. Nine APL patients were identified with 5 being in the eldest cohort. Only 3(33.3%) survived 6 months. None of the patients with AML-NOS were alive at 6 months.
CONCLUSIONS: Acute leukemia in the elderly population remains a challenge with poor outcomes despite considering patient\'s age and performance status.

BACKGROUND: B-lymphoblastic lymphoma (B-LBL) with BCR/ABL mutation (Ph+ B-LBL) is a rare type of cancer in both childhood and adults. Its clinical manifestations are similar to those of other types lymphoma. However, the targeted therapy can substantially improve the outcome of Ph+ B-LBL.
METHODS: A 19-year-old male with blood type O, Rh+ was admitted into our hospital on August 14, 2018, due to a recurrent fever and hypocytosis for 6 months.
METHODS: Routine blood exam showed pancytopenia. Bone marrow sample flow cytometry (FCM) exam showed abnormal cells were 2.27% of the nucleated cells, and was classified as the abnormal early B-lineage lymphoblastic cells. FISH testing showed the BCR/ABL positive cells were 13.6%. Karyotype analysis showed the 46, XY, t(9;22)(q34;q11). Molecular analysis of BCR/ABL mutation on ABL kinase showed that BCR/ABL T315I mutation. Patient was diagnosed with B-LBL with BCR/ABL mutation (Ph+ B-LBL).
METHODS: The patient was given chemotherapy with VDPI regimen (Vinorelbine, daunorubicin, prednisone, imatinib).
RESULTS: The patient achieved complete remission after 2 courses\' treatment, followed by one course of clarithromycin regimen and another two courses of VDPI regimen. Patient remains in complete remission as of March 10, 2021.
CONCLUSIONS: In B-LBL, a BCR/ABL mutation can happen in some of these patients. It is important to guide the pathologist to perform appropriate gene mutation detection, in addition to routine Immunohistochemistry test, to ensure an accurate diagnosis and use the targeted agent for treatment. According to the literature and our results, it seems that intensive chemotherapy plus TKI regimen is effective in inducing complete remission, and allo-SCT should be used as a long-term strategy.

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Despite the encouraging clinical progress of chemotherapeutic agents in cancer treatment, innovation and development of new effective anticancer candidates still represents a challenging endeavor. With 15 million death every year in 2030 according to the estimates, cancer has increased rising of an alarm as a real crisis for public health and health systems worldwide. Therefore, scientist began to introduce innovative solutions to control the cancer global health problem. One of the promising strategies in this issue is the multitarget or smart hybrids having two or more pharmacophores targeting cancer. These rationalized hybrid molecules have gained great interests in cancer treatment as they are capable to simultaneously inhibit more than cancer pathway or target without drug-drug interactions and with less side effects. A prime important example of these hybrids, the HDAC hybrid inhibitors or referred as multitargeting HDAC inhibitors. The ability of HDAC inhibitors to synergistically improve the efficacy of other anti-cancer drugs and moreover, the ease of HDAC inhibitors cap group modification prompt many medicinal chemists to innovate and develop new generation of HDAC hybrid inhibitors. Notably, and during this short period, there are four HDAC inhibitor hybrids have entered different phases of clinical trials for treatment of different types of blood and solid tumors, namely; CUDC-101, CUDC-907, Tinostamustine, and Domatinostat. This review shed light on the most recent hybrids of HDACIs with one or more other cancer target pharmacophore. The designed multitarget hybrids include topoisomerase inhibitors, kinase inhibitors, nitric oxide releasers, antiandrogens, FLT3 and JAC-2 inhibitors, PDE5-inhibitors, NAMPT-inhibitors, Protease inhibitors, BRD4-inhibitors and other targets. This review may help researchers in development and discovery of new horizons in cancer treatment.

To investigate the effects of mitoxantrone and daunorubicin in induced chemotherapy on complete remission (CR), death during induction therapy, overall survival (OS), disease-free survival (DFS), and relapse in patients of all ages with acute myeloid leukemia (AML).
We searched published reports at the Medline, Embase, and Cochrane Databases as well as other databases from inception through July 2019. There was no restriction on date of publication or language (PROSPERO registration CRD42018095843).
We enrolled 12 randomized controlled trials that included data of 4583 AML patients whose disease was untreated or relapsed/refractory, and compared the CR, death during induction therapy, DFS, and OS between mitoxantrone and daunorubicin. Mitoxantrone significantly increased the CR rate (relative risk = 1.07; 95% confidence interval [CI], 1.01, 1.14; P = .03) and DFS (hazard ratio = 0.87; 95% CI, 0.79, 0.96; P = .005) compared to daunorubicin. However, there was no significant difference in death during induction therapy (relative risk = 1.00; 95% CI, 0.81, 1.24; P = .99) and OS (hazard ratio = 0.94; 95% CI, 0.87, 1.01; P = .077) between the two drugs.
Although more studies are needed to compare mitoxantrone with higher-dose daunorubicin, the results showed that compared to daunorubicin, mitoxantrone can significantly improve CR and DFS in patients of all ages. These findings suggest that mitoxantrone may be a better choice than daunorubicin as an induction chemotherapy agent for AML patients, especially in developing countries.

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On June 28, 2018, the Committee for Medicinal Products for Human Use adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Vyxeos, intended for the treatment of acute myeloid leukemia (AML). Vyxeos was designated as an orphan medicinal product on January 11, 2012. The applicant for this medicinal product was Jazz Pharmaceuticals Ireland Limited. Vyxeos is a liposomal formulation of a fixed combination of daunorubicin and cytarabine, antineoplastic agents that inhibit topoisomerase II activity and also cause DNA damage. The strength of Vyxeos is 5 units/mL, where 1 unit equals 1.0 mg cytarabine plus 0.44 mg daunorubicin. The marketing authorization holder Jazz Pharmaceuticals had found that this was an optimal ratio for the efficacy of the product. Study CLTR0310-301, a phase III, multicenter, randomized, trial of Vyxeos (daunorubicin-cytarabine) liposome injection versus standard 3+7 daunorubicin and cytarabine in patients aged 60-75 years with untreated high-risk (secondary) AML, showed a statistically significant difference between the two groups in overall survival (OS) with a median OS of 9.56 months in the daunorubicin-cytarabine arm compared with 5.95 months for standard chemotherapy (hazard ratio, 0.69; 95% confidence interval, 0.52-0.90; one-sided p = .003). The most common side effects were hypersensitivity including rash, febrile neutropenia, edema, diarrhea/colitis, mucositis, fatigue, musculoskeletal pain, abdominal pain, decreased appetite, cough, headache, chills, arrhythmia, pyrexia, sleep disorders, and hypotension. IMPLICATIONS FOR PRACTICE: Vyxeos has demonstrated a clinically significant improvement in overall survival compared with the standard of care 7+3 in the proposed population of patients with newly diagnosed acute myeloid leukemia (AML) with myelodysplasia-related changes and therapy-related AML. This is remarkable given the very poor prognosis of these patients and their unmet medical need. Secondary endpoints support the primary outcome, in particular an increased rate of hematopoietic stem cell transplantation, which is potentially the only curative treatment in AML.

On February 22, 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product gemtuzumab ozogamicin (Mylotarg; Pfizer, New York City, NY), intended for the treatment of acute myeloid leukemia. Mylotarg was designated as an orphan medicinal product on October 18, 2000. The applicant for this medicinal product was Pfizer Limited (marketing authorization now held by Pfizer Europe MA EEIG).The demonstrated benefit with Mylotarg is improvement in event-free survival. This has been shown in the pivotal ALFA-0701 (MF-3) study. In addition, an individual patient data meta-analysis from five randomized controlled trials (3,325 patients) showed that the addition of Mylotarg significantly reduced the risk of relapse (odds ratio [OR] 0.81; 95% CI: 0.73-0.90; p = .0001), and improved overall survival at 5 years (OR 0.90; 95% CI: 0.82-0.98; p = .01) [Lancet Oncol 2014;15:986-996]. The most common (>30%) side effects of Mylotarg when used together with daunorubicin and cytarabine are hemorrhage and infection.The full indication is as follows: \"Mylotarg is indicated for combination therapy with daunorubicin (DNR) and cytarabine (AraC) for the treatment of patients age 15 years and above with previously untreated, de novo CD33-positive acute myeloid leukemia (AML), except acute promyelocytic leukemia (APL).\"The objective of this article is to summarize the scientific review done by the CHMP of the application leading to regulatory approval in the European Union. The full scientific assessment report and product information, including the Summary of Product Characteristics, are available on the European Medicines Agency website (www.ema.europa.eu). IMPLICATIONS FOR PRACTICE: This article reflects the scientific assessment of Mylotarg (gemtuzumab ozogamicin; Pfizer, New York City, NY) use for the treatment of acute myeloid leukemia based on important contributions from the rapporteur and co-rapporteur assessment teams, Committee for Medicinal Products for Human Use members, and additional experts following the application for a marketing authorization from the company. It\'s a unique opportunity to look at the data from a regulatory point of view and the importance of assessing the benefit-risk.

Diffuse large B-cell lymphoma is categorized by gene expression profiling into germinal center (GCB) and activated B-cell (ABC) subtype, also referred to as non-germinal center B-cell (non-GCB) by immunohistochemistry. ABC DLBCL is characterized by NF-κB pathway activation and high expression of IRF4/MUM1, a key transcription factor in B cell differentiation. Patients with ABC DLBCL have a significantly worse outcome when treated with standard chemotherapy (R-CHOP). Lenalidomide have shown activity in the ABC-DLBCL in combination with R-CHOP. But about 40% of patients remain resistant. We present the experience of treatment of a patient with generalized non-GCB-DLBCL using the intensive protocol R-mNHL-BFM-90 with lenalidomide.