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Background We studied humoral responses after coronavirus disease 2019 (COVID-19) vaccination across varying causes of immunodeficiency. Methods Prospective study of fully vaccinated immunocompromised adults (solid organ transplant [SOT], hematologic malignancy, solid cancers, autoimmune conditions, human immunodeficiency virus [HIV]) versus nonimmunocompromised healthcare workers (HCWs). The primary outcome was the proportion with a reactive test (seropositive) for immunoglobulin G to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity. Results A total of 1271 participants enrolled: 1099 immunocompromised and 172 HCW. Compared with HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (P <.01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus messenger RNA (mRNA)-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman r  = 0.89, P  < .0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW. Conclusions Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCWs. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency. [ABSTRACT FROM AUTHOR]

We measured severe acute respiratory syndrome coronavirus 2 immunoglobulin G responses in 67 patients with hematological malignancies after 2 messenger RNA vaccine doses. Forty-six percent were nonresponders; patients with B-cell chronic lymphocytic leukemia were at highest risk (77% nonresponders). Patients with hematological malignancies should continue wearing masks and socially distancing. Studies of revaccination, boosters, and humoral immune correlates of protection are needed. [ABSTRACT FROM AUTHOR]

Background aims Activated NK cells (aNK) generated by expansion of a human interleukin-2–dependent NK cell line (NK-92) were shown to mediate strong anti-leukemia activity. This phase 1 study evaluated feasibility, safety, and activity of aNK cells adoptively transferred to patients with refractory/relapsed acute myeloid leukemia (AML). In addition, effects of these aNK cells on the patient's immune system were evaluated. Methods Two cell-dose levels (1 × 10 9 cells/m 2 and 3 × 10 9 cells/m 2 ) were used. One treatment course consisted of two infusions of the same cell dose, each cell infusion delivered 24 h apart. The aNK cells were administered in the outpatient setting. Results Seven patients with refractory/relapsed AML were treated with a total of 20 aNK cell infusions. None of the 7 patients experienced dose-limiting toxicities during the aNK cell administration or during 21 days of the post-infusion observation period. No grade 3–4 toxicities (probable or definite) related to aNK cell infusions occurred. Activity was transient in 3 of 7 patients. No significant changes in the patient's lymphocyte counts, subsets frequency, phenotype or activity were observed post-infusion. Cell dose-dependent effects in the plasma levels of several cytokines were observed. Discussion The trial demonstrated the safety and feasibility of adoptive cell therapy with “off-the-shelf” aNK cells in patients with refractory/relapsed AML. These data provide the foundation for future combination immunotherapy trials and for the optimization of aNK cell based therapies in patients with AML. [ABSTRACT FROM AUTHOR]

Organ transplant recipients are at an increased risk for subsequent cancer including acute myeloid leukemia ( AML). Treatment of AML following solid transplantation represents a clinical challenge as most patients have significant comorbidities at the time of AML diagnosis. In this study, we evaluated the treatment and outcomes of patients who developed AML following solid organ transplantation at our institution and reviewed the literature on outcomes for these patients. The study cohort consisted of 14 patients (median age 66 years, range 52-77 years) with newly diagnosed AML following solid organ transplantation. The median interval time between solid organ transplantation and AML diagnosis was 72 months (range 15-368 months). Seven patients received standard induction chemotherapy, four patients received intermediate type therapy, and the remaining three patients were deemed not fit for therapy and received palliative and supportive care. Six of the 11 treated patients (55%) achieved complete remission ( CR). The median overall survival ( OS) for all patients was 6 months. The median OS for the patients who achieved complete remission after therapy was 17 months and 2 months for the remaining patients. Despite initial CR, relapse rates are still high, suggesting that alternative strategies for post-remission therapies are warranted. [ABSTRACT FROM AUTHOR]

Hyperleukocytosis is present in 5 to 20 percent of patients with newly diagnosed acute myeloid leukemia (AML). The management of hyperleukocytosis, when symptoms of leukostasis occur, includes intensive supportive care and interventions for rapid cytoreduction. Leukapheresis is a rapid and effective means of cytoreduction and has been used in AML patients. In the current study, we evaluated the outcomes of 68 newly diagnosed AML patients that underwent leukapheresis and the effects of leukapheresis on various laboratory parameters. A total of 127 leukapheresis cycles were performed. The median number of leukapheresis cycles was 2 (range, 1–8). The overall survival for all patients was 4.2 months (95% CI 1.2–9.7 months). The median overall survival for patients who achieved complete remission after induction chemotherapy was significantly higher (19.1 months [95% CI 12.1–41.8 months]) than patients that did not achieve complete remission (0.46 months [95% CI 0.33–0.99 months]). Stepwise logistic regression demonstrated that elevated number of peripheral blasts, low platelet count and elevated bilirubin at AML diagnosis were predictive of death within a week . Leukapheresis was effective in reducing the peripheral blood leukocytes and leukemia blasts and was a safe procedure with regard to organ function, coagulation parameters, red blood cells and platelet count. The high initial response rates in newly diagnosed AML patients fit to receive intensive chemotherapy suggest that leukapheresis could be beneficial in reducing the complications associated with hyperleukocytosis until systemic intensive chemotherapy commences. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 62-year-old woman whose necrotic plaque on her left cheek was found to be a classic blastic plasmacytoid dendritic-cell neoplasm. Topics discussed include findings on positron-emission tomography-computed tomography (PET-CT) scan, analysis of a bone marrow specimen, and the probable pathogenic role of B cell lymphoma 2 (BCL2) in blastic plasmacytoid dendritic-cell neoplasm and the potential therapeutic role of the anti-BCL2 venetoclax in their treatment.

Twenty patients (11%) had favorable risk cytogenetics, 108 patients (62%) had intermediate risk cytogenetics, and 47 patients (27%) had unfavorable risk cytogenetics. Prediction at AML diagnosis that a patient would not respond to standard induction chemotherapy would lead to the use of other therapies sparing the patient from the toxicities of treatments that prove to be ineffective. Genomic profiling has allowed major advances in unraveling the complex molecular signature of acute myeloid leukemia (AML) and has informed us of the prognosis and survival of AML patients [[1]]. [Extracted from the article]

The article focuses on the importance of anti-BCL2 agent venetoclax in the treatment of blastic plasmacytoid dendritic-cell neoplasm. It talks about the clinical trials conducted where the patient was given venetoclax after receiving cytotoxic therapy. It tells about venetoclax and cytotoxic therapy kept the diseases in control.

109 patients achieved a complete remission (CR), 5 patients achieved complete remission with incomplete hematologic recovery (CRi) and 2 patients achieved a morphologic leukemia-free state (MLFS). Acute myeloid leukemia (AML) is a life-threatening disease that requires urgent treatment. Of all patients, 23 (18%) patients had flow cytometric abnormalities and 105 (82%) patients did not. A similar approach is noted by Cheson et al. who recommend repeating the bone marrow biopsy if blasts are 5-20% in the bone marrow biopsy, as in some patients the increased blasts disappear in the next bone marrow biopsy [[4]]. [Extracted from the article]

Purpose: Central venous catheters (CVCs) are widely used in acute myeloid leukemia (AML) patients. Complications associated with CVCs are frequently encountered and contribute to morbidity and mortality. Prospective studies investigating and comparing complications of different types of CVCs in AML patients and their effects on the quality of life are limited. Methods: We conducted a prospective observational study and evaluated the complications associated with the use of CVCs in adult AML patients during induction chemotherapy and evaluated quality of life outcomes as reported by the patients during and after their hospitalization. Results: Fifty newly diagnosed patients with AML (median age, 59 years) who received intensive induction chemotherapy were enrolled in the study. Twenty-nine patients (58%) had a peripherally inserted central catheters (PICCs) placed and 21 (42%) patients received a Hickmann tunneled central catheter (TCC). Three percent of cases developed catheter-related thrombosis in PICCs and no thrombosis in TCCs. Catheter-related bloodstream infection was diagnosed in 8% of patients. CVC occlusion occurred in 44 patients (88%). The total number of occlusion events was 128; 97% of patients with PICCs and 76% of patients with TCCs (p = 0.003). All patients reported that the use of CVC simplified their course of treatment. Most patients reported similar restrictions in activity associated with TCCs and PICCs. Conclusion: The present study demonstrates that thrombosis and catheter-related bloodstream infections remain important complications of CVCs in AML patients. Occlusion rates were higher with the use of PICCs and the use of CVCs impacted the quality of life. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 36-year-old man who was diagnosed with Fibroblast growth factor receptor 1 (FGFR1) associated myeloid neoplasm with increased mast cells.

We administered severe acute respiratory syndrome coronavirus-2 viral-specific T cells (VSTs) under emergency investigational new drug applications to 6 immunocompromised patients with persistent coronavirus disease 2019 (COVID-19) and characterized clinical and virologic responses. Three patients had partial responses after failing other therapies but then died. Two patients completely recovered, but the role of VSTs in recovery was unclear due to concomitant use of other antivirals. One patient had not responded to 2 courses of remdesivir and experienced sustained recovery after VST administration. The use of VSTs in immunocompromised patients with persistent COVID-19 requires further study. [ABSTRACT FROM AUTHOR]

The article presents a study which described adherence levels across post-hematopoietic cell transplantation (HCT) medical regimen tasks and examines the role of dyadic factors in the successful adherence in HCT. Topics discussed include the characteristics of the patients involved in the study, and associations between adherence and demographic, psychological, and clinical factors, and clinical implications.

Background: Mu heavy chain disease is a rare lymphoid neoplasm characterized by vacuolated bone marrow plasma cells and secretion of defective mu immunoglobulin heavy chains. The biological basis of mu heavy chain disease is poorly understood. Case presentation: We report a case of mu heavy chain disease with MYD88 L265P mutation and deletion of 6q, genetic aberrations that are both strongly associated with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Identification of the truncated mu immunoglobulin was facilitated by mass spectrometric analysis of the patient's serum. Conclusions: Mu heavy chain disease has been described as similar to chronic lymphocytic leukemia; however, the frequency of lymphocytosis in mu heavy chain disease has not been previously reported. We reviewed all previously published mu heavy chain disease reports and found that lymphocytosis is uncommon in the entity. This finding, along with the emerging genetic feature of recurrent MYD88 mutation in mu heavy chain disease, argues that at least a significant subset of cases are more similar to lymphoplasmacytic lymphoma than to chronic lymphocytic leukemia. [ABSTRACT FROM AUTHOR]

Background: CARTITUDE-1 aimed to assess the safety and clinical activity of ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell therapy with two B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed or refractory multiple myeloma with poor prognosis.Methods: This single-arm, open-label, phase 1b/2 study done at 16 centres in the USA enrolled patients aged 18 years or older with a diagnosis of multiple myeloma and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who received 3 or more previous lines of therapy or were double-refractory to a proteasome inhibitor and an immunomodulatory drug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. A single cilta-cel infusion (target dose 0·75 × 106 CAR-positive viable T cells per kg) was administered 5-7 days after start of lymphodepletion. The primary endpoints were safety and confirmation of the recommended phase 2 dose (phase 1b), and overall response rate (phase 2) in all patients who received treatment. Key secondary endpoints were duration of response and progression-free survival. This trial is registered with ClinicalTrials.gov, NCT03548207.Findings: Between July 16, 2018, and Oct 7, 2019, 113 patients were enrolled. 97 patients (29 in phase 1b and 68 in phase 2) received a cilta-cel infusion at the recommended phase 2 dose of 0·75 × 106 CAR-positive viable T cells per kg. As of the Sept 1, 2020 clinical cutoff, median follow-up was 12·4 months (IQR 10·6-15·2). 97 patients with a median of six previous therapies received cilta-cel. Overall response rate was 97% (95% CI 91·2-99·4; 94 of 97 patients); 65 (67%) achieved stringent complete response; time to first response was 1 month (IQR 0·9-1·0). Responses deepened over time. Median duration of response was not reached (95% CI 15·9-not estimable), neither was progression-free survival (16·8-not estimable). The 12-month progression-free rate was 77% (95% CI 66·0-84·3) and overall survival rate was 89% (80·2-93·5). Haematological adverse events were common; grade 3-4 haematological adverse events were neutropenia (92 [95%] of 97 patients), anaemia (66 [68%]), leukopenia (59 [61%]), thrombocytopenia (58 [60%]), and lymphopenia (48 [50%]). Cytokine release syndrome occurred in 92 (95%) of 97 patients (4% were grade 3 or 4); with median time to onset of 7·0 days (IQR 5-8) and median duration of 4·0 days (IQR 3-6). Cytokine release syndrome resolved in all except one with grade 5 cytokine release syndrome and haemophagocytic lymphohistiocytosis. CAR T-cell neurotoxicity occurred in 20 (21%) patients (9% were grade 3 or 4). 14 deaths occurred in the study; six due to treatment-related adverse events, five due to progressive disease, and three due to treatment-unrelated adverse events.Interpretation: A single cilta-cel infusion at the target dose of 0·75 × 106 CAR-positive viable T cells per kg led to early, deep, and durable responses in heavily pretreated patients with multiple myeloma with a manageable safety profile. The data from this study formed the basis for recent regulatory submissions.Funding: Janssen Research & Development and Legend Biotech. [ABSTRACT FROM AUTHOR]

Purpose: Given the complexities and risks of allogeneic HCT, patients and their family caregivers may experience elevated psychological distress, including symptoms of anxiety and depression, in anticipation of the procedure. Patients and caregivers also bring with them their pre-HCT experiences of diagnosis, prior treatment, and associated burdens, thus potentially compounding their acute distress. Identification of clinical, psychosocial, and sociodemographic factors related to pre-HCT distress would allow targeting of patients and caregivers who may require assistance during the HCT process.Methods: Consecutive patients (n = 111) and their caregivers (n = 110) completed measures of anxiety, depression, cancer distress, perceived threat, perceived control, self-efficacy, relationship quality, and physical quality of life in the week before HCT. Multivariate linear regression analysis was used to identify factors associated with patient and caregiver anxiety or depression, including disease type, donor type, and patient and caregiver sociodemographic, health-related, and psychosocial factors.Results: Family caregivers had higher levels of anxiety and depression symptoms than patients. Thirty percent of caregivers vs. 17% of patients met criteria for clinically significant anxiety and a lesser amount (5% for both) met criteria for clinically significant depression. Patient anxiety was related to younger age (b = - 0.22, p = 0.005) and greater cancer-related distress (b = 0.59, p < 0.001), while caregiver anxiety was related to lower self-efficacy (b = - 0.19, p = 0.011) and greater cancer-related distress (b = 0.58, p < 0.001). Similarly, patient depression was related to lower perceived control (b = - 0.17, p = 0.050), greater cancer-related distress (b = 0.34, p = 0.005), and lower physical functioning (b = - 0.26, p = 0.008), while caregiver depression was related to greater cancer-related distress (b = 0.46, p < 0.001).Conclusions: Family caregivers may be more emotionally vulnerable than patients before HCT and in need of additional assistance. Cancer-related distress was the strongest correlate of anxiety and depression in both patients and caregivers, suggesting that distress related to their cancer experience and its consequences plays a major role in their emotional functioning prior to HCT. [ABSTRACT FROM AUTHOR]

Src family kinases (SFKs) are hyperactivated in acute myeloid leukemia (AML). SFKs impede the retinoic acid receptor, and SFK inhibitors enhance all-trans retinoic acid (ATRA)-mediated cellular differentiation in AML cell lines and primary blasts. To translate these findings into the clinic, we undertook a phase-I dose-escalation study of the combination of the SFK inhibitor dasatinib and ATRA in patients with high-risk myeloid neoplasms. Nine subjects were enrolled: six received 70 mg dasatinib plus 45 mg/m2 ATRA daily, and three received 100 mg dasatinib plus 45 mg/m2 ATRA daily for 28 days. Headache and QTc prolongations were the only two grade 3 adverse events observed. No significant clinical responses were observed. We conclude that the combination of 70 mg dasatinib and 45 mg/m2 ATRA daily is safe with acceptable toxicity. Our results provide the safety profile for further investigations into the clinical efficacy of this combination therapy in myeloid malignancies. [ABSTRACT FROM AUTHOR]

We carried out a retrospective study on newly diagnosed AML patients to identify the risk factors associated with intensive care unit (ICU) intervention. One hundred and twenty consecutive AML patients were included. The median cycle of induction therapy (IT) was 2 (range 1–4). Ten patients (8%) needed ICU intervention during IT. The median time from first IT to ICU transfer was 16 days (range 2–88 days). Three patients required vasopressor/s, three mechanical ventilation, and four both. The cumulative probability for ICU intervention rose progressively with increasing cycles of IT received, from 2.5% during first induction to 27.5% at fourth induction. Age, sex, presentation white cell counts and coagulation profiles, cytogenetics, pre-chemotherapy ventricular ejection fractions, and prior chemoradiation were not risk factors. Univariate analysis identified a history of inflammatory bowel disease (IBD) (p = 0.004) (RR = 5.7; p = 0.03) and positive blood cultures (BC) (p = 0.03) (RR = 3; p = 0.06) as significant risks. Multivariate analysis found a history of IBD as the only significant factor (p = 0.03), while positive BC (p = 0.1) trending towards significance. AML patients with a history of IBD and positive BC are at increased risks for ICU intervention during IT. [ABSTRACT FROM AUTHOR]

Background/Aims: Relapse is a leading cause of mortality after allogeneic hematopoietic cell transplantation (HCT). Hypomethylating agents (HMAs) have immunomodulatory properties, including augmenting tumor antigen presentation that may enhance the graft-versus-leukemia effect. Moreover, inhibitory effects on T-cell activation and cytokine production may lead to a lower incidence of graft-versus-host disease (GVHD). Our aim was to describe outcomes in patients treated with HMAs for relapse after HCT. Methods: Subjects were retrospectively identified as patients with relapse or loss of donor chimerism after HCT for myeloid malignancies treated with HMAs at the University of Pittsburgh. Results: Thirteen patients were identified, with a median age of 57 years and a median time to relapse of 98 days. Nine of 12 (75%) evaluable patients had a complete remission (CR). Grade I-IV acute GVHD involving the liver occurred in 6 patients. Cases of acute liver GVHD were diagnosed clinically based on the elevation of liver function tests. The median survival was 14.3 months from the time of relapse. Conclusion: HMAs for relapse after HCT can be effective in inducing a CR. This may be due to epigenetic changes and immunomodulatory effects that enhance the graft-versus-leukemia effect. There may be a risk of GVHD, and further exploration into pathophysiology and predisposing factors are warranted. [ABSTRACT FROM AUTHOR]

Pulmonary nodules (PNs) develop frequently in patients with acute myeloid leukemia (AML). They are of infectious or inflammatory origin. They pose potential challenges to successful hematopoietic progenitor cell (HPC) transplant as they may be niches for infection reactivation or sites susceptible to subsequent infections. We retrospectively analyzed the outcome of 20 AML patients with multiple PNs who underwent allogeneic HPC transplants (12 related, 8 unrelated). There were 13 males and seven females (median age 52 yrs). Nine patients were in CR1, seven in CR2, and four with residual disease. The median times from appearance of PNs and from last positive CT scans to transplant were three and two months, respectively. The median time from pretransplant CT scans to transplant was one month. Multiple PNs were still reported in 5/20 of the pretransplant scans. The PNs in all five patients did not worsen after transplant. Four patients (one with positive pretransplant CT scan) died within the first 100 d after transplant, but none from primary pulmonary pathology. The median survival of this group of patients was 350 d. Our results, therefore, suggest that multiple PNs of uncertain etiology in patients with AML do not impact adversely on the outcome of allogeneic HPC transplant. [ABSTRACT FROM AUTHOR]

Instead of the accurate author name "Jeffrey A. Vos", it displays the wrong author name "Jeffrey A. VosUPMC" in the web article that has been published. B Correction: Diagnostic Pathology 17, 63 (2022) b . https://doi.org/10.1186/s13000-022-01244-1 Following publication of the original article [[1]], the authors found a typo in one of the author names in the author group section. [Extracted from the article]

This multicenter phase 1/2 trial investigated the combination of bendamustine, lenalidomide, and dexamethasone in repeating 4-week cycles as treatment for relapsed refractory multiple myeloma (MM). Phase 1 established maximum tolerated dose (MTD). Phase 2 assessed overall response rate at the MTD. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A total of 29 évaluable patients were enrolled. Median age was 63 years (range 38-80 years). Median number of prior therapies was 3 (range, 1-6). MTD was bendamustine 75 mg/m2 (days 1 and 2), lenalidomide 10 mg (days 1 -21 ), and dexamethasone 40 mg (weekly) of a 28-day cycle. Partial response rate was 52%, with very good partial response achieved in 24%, and minimal response in an additional 24% of patients. Median follow-up was 13 months; median OS has not been reached. One-year OS is 93% (95% confidence interval [CI], 59%-99%). Median PFS is 6.1 months (95% CI, 3.7-9.4 months) with one-year PFS of 20% (95% CI, 6%-41%). Grade 3/4 adverse events included neutropenia, thrombocytopenia, anemia, hyperglycemia, and fatigue. This first phase 1/2 trial testing bendamustine, lenalidomide, and dexamethasone as treatment of relapsed refractory MM was feasible and highly active. [ABSTRACT FROM AUTHOR]

Abstract: The most effective regimen for acute myeloid leukemia (AML) patients who do not achieve complete remission (CR) after two different courses of front-line chemotherapy has not been established. We therefore evaluated the efficacy, toxicity, and prognostic factors for achieving CR following treatment with fludarabine and cytarabine in 25 newly diagnosed AML patients who did not respond to initial therapy with idarubicin and cytarabine followed by mitoxantrone and etoposide. CR was achieved in 32% of patients; in 55% of patients with intermediate-risk karyotype and in 14% with unfavorable-risk. Eight percent died of infectious complications. Median duration of overall survival was 6.6 months (95% CI 3.4 months to ∞); 3.4 months (95% CI 0.8–8.6 months) for patients with an unfavorable-risk karyotype and 18.1 months (95% CI 5.0 months to ∞) with an intermediate-risk karyotype (p =0.02). Our data suggest that poor-risk karyotype patients are unlikely to benefit from third course treatment with fludarabine–cytarabine, and that this regimen merits further investigation in AML patients with good or intermediate-risk karyotype that have persistent leukemia after two courses of front-line chemotherapy. [Copyright &y& Elsevier]

A letter to the editor is presented regarding two cases of de novo acute myeloid leukemia (AML) patients who exhibited Philadelphia chromosome (BCR-ABL) and inversion 16 (CBFB-MYH11).

The article offers information on retrospective study of efficacy and toxicity linked with gemtuzumab ozogamicin (GO) therapy in newly diagnosed elderly acute myeloid leukemia (AML) patients. A brief information on the prevalence of AML and the approval of GO by the U.S. Food and Drug Administration (FDA) in 2000 is presented. The factors potentially predictive of response in previously untreated AML patients were also assessed. It discusses in detail the research findings.

The most effective regimen for patients with acute myeloid leukemia (AML) who do not achieve complete remission (CR) after one course of cytarabine and an anthracycline has not been extensively studied. We evaluated restrospectively the efficacy, toxicity, and prognostic factors for the achievement of CR following mitoxantrone and etoposide in 74 patients with newly diagnosed AML who did not respond to one course of therapy with cytarabine and idarubicin. CR was achieved in 39% of patients; 14% died of infectious complications; no grade 3 or 4 hepatic toxicities were observed. Median duration of overall survival was 9.0 months (95% CI 5.8-14.9 months). The median duration of relapse-free survival was 11.0 months (95% CI: 9.0-19.3 months). A lower CR rate was associated with unfavorable risk status at diagnosis and higher percent blasts. Our data suggest that the combination of etoposide and mitoxantrone is an effective second-course therapy in patients with newly diagnosed AML. [ABSTRACT FROM AUTHOR]

Simple Summary: There is an urgent need to develop new treatments for patients with relapsed/refractory multiple myeloma (RRMM) to address unmet medical needs. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel approach with the potential for long-term disease control. Ciltacabtagene autoleucel (cilta-cel) is a CAR-T treatment studied in patients with RRMM in the CARTITUDE-1 clinical trial and has shown clinically important effects. However, CARTITUDE-1 was a single arm study. The current study compared outcomes for cilta-cel with an external cohort of German patients that are similar to the ones in CARTITUDE-1 to compare the effectiveness of cilta-cel versus established clinical practice. To overcome potential bias, individual patient data were used to adjust for the differences in patient characteristics between cohorts. The results showed substantially better outcomes for cilta-cel on both overall survival and the time to next treatment. These findings highlight cilta-cel's potential as a novel, effective treatment to address unmet treatment needs. Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed/refractory multiple myeloma (RRMM). As cilta-cel was assessed in the single-arm CARTITUDE-1 clinical trial, we used an external cohort of patients from the Therapie Monitor registry fulfilling the CARTITUDE-1 inclusion criteria to evaluate the effectiveness of cilta-cel for overall survival (OS) and time to next treatment (TTNT) vs. real-world clinical practice. Individual patient data allowed us to adjust the comparisons between both cohorts, using the inverse probability of treatment weighting (IPW; average treatment effect in the treated population (ATT) and overlap population (ATO) weights) and multivariable Cox proportional hazards regression. Outcomes were compared in intention-to-treat (HR, IPW-ATT: TTNT: 0.13 (95% CI: 0.07, 0.24); OS: 0.14 (95% CI: 0.07, 0.25); IPW-ATO: TTNT: 0.24 (95% CI: 0.12, 0.49); OS: 0.26 (95% CI: 0.13, 0.54)) and modified intention-to-treat (HR, IPW-ATT: TTNT: 0.24 (95% CI: 0.09, 0.67); OS: 0.26 (95% CI: 0.08, 0.84); IPW-ATO: TTNT: 0.26 (95% CI: 0.11, 0.59); OS: 0.31 (95% CI: 0.12, 0.79)) populations. All the comparisons were statistically significant in favor of cilta-cel. These results highlight cilta-cel's potential as a novel, effective treatment to address unmet needs in patients with RRMM. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses prospective phase I clinical trial that combines gemtuzumab ozogamicin (GO) with mtoxantrone and etoposide for de novo CD33+ diagnosed acute myeloid leukemia (AML) patients who had persistent leukemia following after a course of induction therapy with cytarabine and idarubicin.