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Summary: Among 301 newly diagnosed patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent, 23 (7.6%) experienced major cardiac complications: 15 cardiomyopathy, 5 non‐ST elevation myocardial infarction and/or 7 pericarditis/effusions. Four patients had more than one cardiac complication. Baseline characteristics included median age ± interquartile range; 73 ± 5 years; 87% males; 96% with cardiovascular risk factors; and 90% with preserved baseline ejection fraction. In multivariate analysis, males were more likely (p = 0.02) and DNMT3A‐mutated cases less likely (p < 0.01) to be affected. Treatment‐emergent cardiac events were associated with a trend towards lower composite remission rates (43% vs. 62%; p = 0.09) and shorter survival (median 7.7 vs. 13.2 months; p < 0.01). These observations were retrospectively retrieved and warrant further prospective examination. [ABSTRACT FROM AUTHOR]

This article discusses the use of momelotinib, a JAK2 inhibitor, as a treatment option for myelofibrosis. The study examines the effectiveness of momelotinib in reducing spleen size and alleviating symptoms in patients with myelofibrosis. It also looks at the long-term survival data of patients receiving momelotinib compared to other JAK2 inhibitors. The article highlights the positive impact of momelotinib on anemia and identifies a specific mutation, CALR type 1/like, as a predictor of drug survival and longevity without the need for a stem cell transplant. However, it is important to note that momelotinib and other JAK inhibitors only provide palliative care for myelofibrosis, and more effective disease-modifying drugs are still needed. [Extracted from the article]

Rationale: Pulmonary complications contribute significantly to nonrelapse mortality following hematopoietic stem cell transplantation (HCT). Identifying patients at high risk can help enroll such patients into clinical studies to better understand, prevent, and treat posttransplantation respiratory failure syndromes. Objectives: To develop and validate a prediction model to identify those at increased risk of acute respiratory failure after HCT. Methods: Patients underwent HCT between January 1, 2019, and December 31, 2021, at one of three institutions. Those treated in Rochester, MN, formed the derivation cohort, and those treated in Scottsdale, AZ, or Jacksonville, FL, formed the validation cohort. The primary outcome was the development of acute respiratory distress syndrome (ARDS), with secondary outcomes including the need for invasive mechanical ventilation (IMV) and/or noninvasive ventilation (NIV). Predictors were based on prior case-control studies. Measurements and Main Results: Of 2,450 patients undergoing stem cell transplantation, there were 1,718 hospitalizations (888 patients) in the training cohort and 1,005 hospitalizations (470 patients) in the test cohort. A 22-point model was developed, with 11 points from prehospital predictors and 11 points from posttransplantation or early (<24-h) in-hospital predictors. The model performed well in predicting ARDS (C-statistic, 0.905; 95% confidence interval [CI], 0.870–0.941) and the need for IMV and/or NIV (C-statistic, 0.863; 95% CI, 0.828–0.898). The test cohort differed markedly in demographic, medical, and hematologic characteristics. The model also performed well in this setting in predicting ARDS (C-statistic, 0.841; 95% CI, 0.782–0.900) and the need for IMV and/or NIV (C-statistic, 0.872; 95% CI, 0.831–0.914). Conclusions: A novel prediction model incorporating data elements from the pretransplantation, posttransplantation, and early in-hospital domains can reliably predict the development of post-HCT acute respiratory failure. [ABSTRACT FROM AUTHOR]

Summary: Venetoclax (VEN) is an FDA‐approved selective inhibitor of B‐cell leukaemia/lymphoma‐2 (BCL‐2), used for treating elderly or unfit acute myeloid leukaemia (AML) patients unable to undergo intensive chemotherapy. Combining VEN with hypomethylating agents (HMAs) has shown impressive response rates in high‐risk myelodysplastic syndromes (MDS) and relapsed/refractory AML. However, the efficacy of VEN and HMAs in treating DDX41‐mutated (mDDX41) MDS/AML patients remains uncertain. Despite the favourable prognostic nature of mDDX41 MDS/AML patients, there is a lack of clinical experience regarding their response to different treatment regimens, leading to an unknown optimal therapeutic approach. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplant (allo SCT) for multiple myeloma (MM) is potentially curative in some, while toxic in many others. We retrospectively analyzed 85 patients diagnosed with MM who underwent allo SCT as frontline or salvage therapy between 2000 and 2022 at Mayo Clinic Rochester and examined patient outcomes and prognostic markers. Overall survival (OS), progression free survival (PFS), treatment related mortality (TRM), and relapse rates (RR) were estimated using the Kaplan Meier method and competing risk models. Median follow-up was 11.5 years. Median OS and PFS were 1.7 and 0.71 years, respectively. Five-year OS and PFS were 22.2% and 15.1%, respectively. One-year TRM was 23.5%. Twelve patients demonstrated durable overall survival, living 10+ years beyond their allo SCT. This subgroup was more likely to have no or one prior auto SCT (p = 0.03) and to have been transplanted between 2000 and 2010 (p = 0.03). Outcomes were poor in this cohort with long follow-up, with few patients surviving 5 years or more, and most relapsing or dying within 2 years. We would expect better outcomes and tolerability with an expanded array of novel therapeutics and would prefer them to allo SCT. [ABSTRACT FROM AUTHOR]

We surveyed the performance of ponatinib, as salvage therapy, in a real-world setting of chronic phase chronic myeloid leukemia (CML-CP). Among 55 consecutive patients (median age 49 years) with relapsed/refractory CML-CP, 35 (64%) had failed ≥3 tyrosine kinase inhibitors (TKIs), 35 (64%) were pre-treated with nilotinib, and 14 (28%) harbored ABL1T315I. At start of ponatinib (median dose 30 mg/day), 40 patients were already in complete hematologic (CHR), 4 in complete cytogenetic (CCyR), 3 in major molecular (MMR) remission, while 8 had not achieved CHR (NR). Ponatinib improved the depth of response in 13 (33%), 3 (75%), 2 (66%), and 4 (50%) patients with CHR, CCyR, MMR, and NR, respectively (p = 0.02). At a median follow-up of 42 months, 13 (23%) deaths, 5 (9%) blast transformations, and 25 (45%) allogeneic transplants were recorded. Five/10-year post-ponatinib survival was 77%/58% with no significant difference when patients were stratified by allogeneic transplant (p = 0.94), ponatinib-induced deeper response (p = 0.28), or a post-ponatinib ≥CCyR vs CHR remission state (p = 0.25). ABL1T315I was detrimental to survival (p = 0.04) but did not appear to affect response. Prior exposure to nilotinib was associated with higher risk of arterial occlusive events (AOEs; 11% vs 0%; age-adjusted p = 0.04). Ponatinib starting/maintenance dose (45 vs 15 mg/day) did not influence either treatment response or AOEs. Our observations support the use of a lower starting/maintenance dose for ponatinib in relapsed/refractory CML-CP but a survival advantage for deeper responses was not apparent and treatment might not overcome the detrimental impact of ABL1T315I on survival. The association between prior exposure to nilotinib and a higher risk of post-ponatinib AOEs requires further validation. [ABSTRACT FROM AUTHOR]

Dear Editor, Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly known as agranular CD4 SP + sp /CD56 SP + sp hematodermic neoplasm or blastic natural killer (NK) cell lymphoma was officially recognized as a distinct entity in the 2016 revision of the World Health Organization (WHO) classification of myeloid malignancies [[1]]. In an open-label clinical trial with tagraxofusp in 47 patients with BPDCN, response rates were 90 and 67% among treatment naïve and relapsed patients, respectively [[5]]. 1Overall survival of Mayo Clinic patients with blastic plasmacytoid dendritic cell neoplasm.a Overall survival of 55 patients with blastic plasmacytoid dendritic cell neoplasm stratified by allogeneic stem cell transplant. b Overall survival of 36 patients with blastic plasmacytoid dendritic cell neoplasm stratified by normal vs abnormal karyotype. [Extracted from the article]

To evaluate the impact of killer immunoglobulin-like receptor (KIR) genotyping in allogeneic hematopoietic stem cell transplantation for myeloid disorders at our institution, retrospective KIR genotyping was performed on 77 patients and their 10/10 matched unrelated donors. In a multivariate model including donor age, HLA-DPB1 permissiveness, and presence of donor KIR B/x, an association with overall survival was observed (p =.047). Within the model, increasing donor age increased risk (RR 1.03 [1.00–1.06]/year, p =.046), while donor KIR and HLA-DPB1 permissiveness were not associated with risk (RR 0.51 [0.26–1.03] and RR 0.68 [0.34–1.36]). Grouping recipients by conditioning regimen or limiting the analysis to recipients of peripheral blood stem cells, no association between donor KIR and survival or relapse was identified. No significant associations were observed between overall survival, relapse, grade III-IV acute, or chronic graft versus host disease and presence of KIR B (B/x), quantity of donor KIR B haplotype motifs, or centromeric KIR type (all p >.05). [ABSTRACT FROM AUTHOR]

We retrospectively reviewed 292 patients who received a second line of therapy post ASCT for their light chain amyloidosis. Most patients (40%) were treated with an alkylator + PI ± dex or PI ± dex followed by an alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex (26%), an alkylator ± steroid or steroid monotherapy (19%), a 2nd-gen IMiD + PI ± dex (6%), an alkylator + thalidomide ± dex (5%), or daratumumab-based therapy (4%). The rate of CR or VGPR was 70% among the daratumumab-based group, 62% in the alkylator + PI ± dex or PI ± dex group, 55% in the alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex group, 47% in the 2nd-gen IMiD + PI ± dex group, 24% in the alkylator ± steroid or steroid monotherapy group, and 18% in the alkylator + thalidomide ± dex group. The median OS was NR for the 2nd-gen IMiD + PI ± dex group and the daratumumab group, 130.4 months in the alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex group, 100 months for the alkylator + PI ± dex or PI ± dex group, 36 months for the alkylator ± steroid or steroid monotherapy group, and 21 months for the alkylator + thalidomide ± dex group (P < 0.0001). The median OS was 100 months in patients who received melphalan 200 mg/m2 compared to 41 months in the 140 mg/m2 group (P < 0.0001). In conclusion, patients receiving novel therapy post ASCT and melphalan conditioning dosing at 200 mg/m2 at diagnosis had better outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Orally administered tacrolimus is widely used in hematopoietic cell transplant patients, but multiple clinical situations may arise rendering oral administration infeasible. The undesirable sequelae of intravenous administration, including toxicity, challenges with administration and cost call for innovative solutions to conserve existing supply and optimize safety and efficacy of medication delivery. We sought to demonstrate feasibility of sublingual tacrolimus use and estimate a sublingual-to-oral (SL:PO) conversion ratio in the hematopoietic cell transplant setting. Methods: Ten adults undergoing allogeneic hematopoietic cell transplant received tacrolimus 0.04 mg/kg/dose twice daily. Initial doses were given via sublingual route and a steady state trough level was collected after 4 consecutive doses. Participants were then switched to oral tacrolimus, the dose adjusted for a goal trough 8-12ng/mL, and another steady state trough was drawn. Total daily dose was divided by trough concentration for each route to determine the dosing ratio of SL:PO. Results: Median trough level following sublingual administration was 11.3 ng/mL. Three of these were within goal, 3 were low (4.7–6.4 ng/mL) and 4 were elevated (15.9–18.6 ng/mL). Median SL:PO ratio was 1.02. In 5 participants the SL:PO ratio was <1 (range 0.57–0.94) and in 5 the ratio was ≥1 (range 1.10–1.92). No significant barriers or intolerance to sublingual tacrolimus use were noted. Conclusions: Results demonstrate reliable absorption with sublingual tacrolimus use in patients undergoing hematopoietic cell transplant. Sublingual administration may allow for avoidance of the undesirable complications of IV tacrolimus, such as increased toxicities, required hospitalization for continuous infusion, risk of dose conversion and dilution errors and increased cost. Trial Registry name: Use of Sublingual Tacrolimus in Adult Blood and Marrow Transplant Patients, NCT04041219 https://clinicaltrials.gov/ct2/show/NCT04041219?term=NCT04041219&draw=2&rank=1 [ABSTRACT FROM AUTHOR]

Summary: We report a comparative analysis of patients with therapy‐related acute lymphoblastic leukaemia (tr‐ALL) vs de novo ALL. We identified 331 patients with B‐ALL; 69 (21%) were classified as tr‐ALL. The most common prior malignancies were breast (23·2%) and plasma cell disorders (20·3%). Patients with tr‐ALL were older (median 63·2 vs. 46·2 years, P < 0.001), more often female (66·7% vs. 43·5%, P < 0·001), and more likely to have hypodiploid cytogenetics (18·8% vs. 5·0%, P < 0·001). In multivariable analysis, patients with tr‐ALL were less likely to achieve complete remission [odds ratio (OR) = 0·16, P < 0·001] and more likely to be minimal residual disease‐positive (OR = 4·86, P = 0·01) but had similar OS after diagnosis and allo‐haematopoietic cell transplantation. [ABSTRACT FROM AUTHOR]

Summary: Institutional database search (1999–2020) for acute myeloid leukaemia (AML) identified 109 cases of myeloid sarcoma (MS), of which 19 were isolated and presented de novo. The latter displayed longer survival (median 78 months), compared to MS with synchronous intramedullary AML (n = 32; median 16 months) and de novo AML without MS (n = 729; median 22 months; P = 0·13). However, the difference in survival was no longer apparent after accounting for bone marrow cytogenetic risk status (P = 0·67). Treatment‐induced MS tumour resolution was not affected by the presence of intramedullary disease (P = 0·61). The current study clarifies the prognosis of de novo isolated MS, in the context of AML. [ABSTRACT FROM AUTHOR]

B shows a higher frequency of deaths in patients with multiple organ involvement compared to single organ involvement (33% versus 17%, P = 0.02*) in patients with clinically-relevant short telomeres (telomere length <=10th centile in lymphocytes). At a median follow-up of 15 (95% CI 13-17) months, 124 (78%) patients were alive with 34 (22%) deaths; higher frequency in non-transplanted (untreated) patients with multiple organ involvement compared with single organ involvement (33 versus 17%, I P i = 0.02, Fig. Among the 9 (64%) patients who underwent genetic testing (4 targeted NGS panels, 4 ES-Slice, and 1 WES) in this group, 4 (44%) patients were found to have pathogenic variant (all I TERT i ) and 2 (22%) patients were detected to have a VUS (both I RTEL1 i ). Among patients with short telomeres (TL in lymphocytes <=10%, I n i = 158, 146 adults), only 17% (9/54 tested patients) were positive for pathogenic variants. [Extracted from the article]

In comparison to Ph-pos and Ph-neg ALL, our findings show that patients with Ph-like ALL present at a younger age and with a higher WBC count. Of the 365 patients, 33 (9%) patients with Ph-like ALL were identified; of these, 22 (67%) had I CRLF2 i rearrangements, 5 (12%) had I JAK-STAT i pathway alterations or I EPOR i rearrangements, and 6 (18%) patients had I ABL i -class fusions (Supplementary Table S1). There were no statistically significant differences in outcomes between the three major groups (Ph-like, Ph-pos, and Ph-neg ALL) after allo-HCT (Fig. Patients with Ph-like ALL were significantly younger, with a median age of 39 years (compared with 50 years for patients with Ph-pos and 49 years for Ph-neg ALL; I P i = 0.01) and more likely to be of Hispanic ethnicity (28.1%, vs. 11.7% for Ph-pos and 14.1% for Ph-neg, I P i = 0.07). [Extracted from the article]

Background: Neutropenia is a risk factor for development of infections; however, the direct effect of neutropenia on development of bloodstream infection (BSI) is not known. D‐index, which is area between the neutrophil time curve and a neutrophil count of 0.5 × 109/L, incorporates the combined effect of severity and duration of neutropenia. We aimed to evaluate whether D‐index can be used as a marker for BSI in patients with allogeneic stem cell transplantation. Method: We conducted a retrospective cohort study of patients undergoing allogeneic stem cell transplantation between January 1, 2005, and September 30, 2015. The primary outcome measure was the development of BSI within 30 days of transplantation. Results: A total of 714 patients were included in the study of whom 101 developed BSI. Patients with BSI had a significantly higher median D‐index value compared with patients who did not have BSI (4990 vs. 3570, P <.001). As a marker, the performance of the D‐index was similar to that of the duration of profound neutropenia (P =.18) and significantly better than the total duration of neutropenia (P =.001). Conclusion: The D‐index performed better than the total duration of neutropenia as a marker for BSI in patients with allogeneic stem cell transplantation. There was no difference between D‐index and, a more easily calculable indicator, duration of profound neutropenia. [ABSTRACT FROM AUTHOR]

Rationale: The periengraftment respiratory distress syndrome (PERDS) is an early important cause of morbidity following autologous hematopoietic cell transplantation (HCT). There are few contemporary data describing PERDS. Objectives: To determine prevalence, risk factors, and outcomes of PERDS after autologous HCT. Methods: This was a historical cohort study of adults undergoing autologous HCT at Mayo Clinic, Rochester, Minnesota, between 2005 and 2016. PERDS was defined as 1) respiratory failure requiring supplemental oxygen within 5 days on either side of the neutrophil engraftment date, 2) new pulmonary opacities on chest imaging, and 3) exclusion of an infectious or cardiac etiology to explain the clinical presentation. Results: Of 3,473 patients undergoing autologous HCT, 167 (4.8%) developed PERDS. Radiographic changes preceded engraftment in 77% of cases. In a multivariable regression model, risk factors for PERDS included female sex (odds ratio [OR], 1.73; P = 0.001), the number of preengraftment platelet transfusions (OR, 1.22; P = 0.002), and more rapid engraftment (OR, 0.72 per day longer; P < 0.001). PERDS cases were more likely to be admitted to the intensive care unit (47.3% vs. 9.5%, P < 0.001) and require intubation (20.4% vs. 1.6%, P < 0.001). In an adjusted 100-day death analysis, those diagnosed with PERDS were more likely to die (hazard ratio, 3.1; 95% confidence interval, 1.5-6.2; P = 0.002). Conclusions: PERDS is a common complication of autologous HCT and is associated with increased mortality and healthcare use. Radiographic evidence of pulmonary involvement precedes hematopoietic recovery. A larger number of platelet transfusions and more rapid engraftment appear to increase risk for PERDS. [ABSTRACT FROM AUTHOR]

Rationale: Acute respiratory distress syndrome (ARDS) is a common complication after hematopoietic stem cell transplantation (HCT) and is a major contributor to nonrelapse mortality. Objectives: To better understand pretransplant risk factors for developing ARDS after HCT. Methods: This is a single-center observational study comparing risk factors for ARDS development in 164 patients who went on to develop post-HCT ARDS compared with 492 patients who did not. The patients were matched 1 to 3 on age, sex, type of transplant (allogeneic vs. autologous), and underlying disease. Pertinent risk factors were analyzed separately in multivariable conditional logistic regression after adjustment for a priori variables known to be associated with ARDS development. Results: Patients with ARDS were more likely to have a lower pretransplant pulmonary function as measured by forced vital capacity (FVC) (odds ratio [OR], 0.54 [0.42-0.70] per liter increase in FVC; P < 0.001), forced expiratory volume in one second (FEV1) (OR, 0.52 [0.38-0.71] per liter increase in FEV1; P < 0.001) and diffusing capacity (OR, 0.92 [0.88-0.96] per ml/min/mm Hg increase in diffusing capacity; P < 0.001). Several laboratory indices were predictive of subsequent ARDS development including elevated AST (aspartate aminotransferase) (OR, 1.01 [1.00-1.01]; P < 0.008), lower serum albumin (OR, 0.44 [0.30-0.66]; P < 0.001), lower pretransplant hemoglobin (OR, 0.82 [0.73-0.92]; P = 0.001), and lower leukocyte count (OR, 0.88 [0.79-0.99]; P < 0.03). Patients who went on to develop ARDS were more likely to have been hospitalized in the year before the transplant (OR, 1.11 [1.04-1.20]; P = 0.003), and required invasive or noninvasive ventilation during that hospitalization. Lastly, patients with ARDS were significantly more likely to have received carboplatin, thalidomide, methotrexate, and cisplatin than the non-ARDS control subjects. Conclusions: Several risk factors for developing ARDS after HCT are identifiable at the time of transplantation, well before the development of critical illness and ARDS. The identification of risk factors long before ARDS develops is relatively unique to the HCT population. Further work is needed to develop usable risk prediction tools in this setting. [ABSTRACT FROM AUTHOR]

Background: Diffuse alveolar hemorrhage (DAH) is an uncommon complication of hematopoietic stem cell transplantation (HCT) that carries high morbidity and mortality. Limited contemporary data are available regarding the incidence, outcomes, and risk factors for DAH.Research Question: What are the incidence, outcomes, and risk factors for DAH developing after HCT?Methods: This was a single-center retrospective cohort study of patients who underwent HCT between January 1, 2005, and December 31, 2016. The incidence and outcomes of DAH development were evaluated. A multivariate logistic regression model was used to analyze differences between survivors and nonsurvivors.Results: Of 4,350 patients undergoing first-time HCT, DAH was diagnosed in 99 (2.3%). DAH was seen in 40 of 3,536 autologous HCT recipients (1.1%) and 59 of 814 allogeneic HCT recipients (7.2%). Mean age was 53 ± 13 years, and median time of DAH diagnosis was 126 days (interquartile range, 19-349 days) after HCT. In-hospital mortality and mortality 1 year after DAH diagnosis were 55.6% and 76.8%, respectively. DAH diagnosis more than 30 days after transplantation (OR, 7.06; 95% CI, 1.65-30.14), low platelet count (OR, 0.98; 95% CI, 0.96-1.0; P = .02), elevated international normalized ratio (INR; OR, 4.08; 95% CI, 0.64-25.88; P = .046) and need for invasive mechanical ventilation (OR, 8.18; 95% CI, 1.9-35.21) were associated with higher in-hospital mortality. Steroid treatment did not alter mortality (P = .80) or length of stay (P = .65). However, among those who received steroids, survival was higher in whose who received modest-dose steroids (< 250 mg methylprednisolone equivalent/d) compared with those who received high-dose steroids (≥ 250 mg methylprednisolone equivalent/d; OR, 0.21; 95% CI, 0.07-0.72).Interpretation: The mortality of DAH after HCT remains high, and DAH can occur long after transplantation. Later development of DAH (>30 days after HCT), need for invasive mechanical ventilation, thrombocytopenia, and elevated INR are all associated with worse outcomes. [ABSTRACT FROM AUTHOR]

However, to date, there has been no published data on the surface expression of PD-1/PD-L1 in EM lesions in AML patients. Initial results of an ongoing Phase 1 trial (NCT01822509) using PD-1 inhibitors for patients with AML after SCT showed resolution of EM leukemia in three of the patients [[12]]. The same patient had negative PD-1/PD-L1 expression from the same breast 6 months before the positive testing. Davids et al study of cytotoxic T-cell leukocyte antigen four inhibitor (ipilimumab 10 mg/kg every 3 weeks) for patients who relapsed after allogeneic transplantation notably showed durable complete remission of four of five patients with EM AML lasting more than a year [[11]]. [Extracted from the article]

Magnesium is an essential element that is involved in critical metabolic pathways. A diet deficient in magnesium is associated with an increased risk of developing cancer. Few studies have reported whether a serum magnesium level below the reference range (RR) is associated with prognosis in patients with diffuse large B cell lymphoma (DLBCL). Using a retrospective approach in DLBCL patients undergoing autologous stem cell transplant (AHSCT), we evaluated the association of hypomagnesemia with survival. Totally, 581 patients eligible for AHSCT with a serum magnesium level during the immediate pre-transplant period were identified and 14.1% (82/581) had hypomagnesemia. Hypomagnesemia was associated with an inferior event-free (EFS) and overall survival (OS) compared to patients with a serum magnesium level within RR; median EFS: 3.9 years (95% CI: 1.63–8.98 years) versus 6.29 years (95% CI: 4.73–8.95 years) with HR 1.63 (95% CI: 1.09–2.43, p = 0.017) for EFS, and median OS: 7.3 years (95% CI: 2.91—upper limit not estimable) versus 9.7 years (95% CI: 6.92–12.3 years) with HR 1.90 (95% CI: 1.22–2.96, p = 0.005) for OS months 0–12, respectively. These findings suggest a potentially actionable prognostic factor for patients with DLBCL undergoing AHSCT. [ABSTRACT FROM AUTHOR]

Between 2004 and 2017, a total of 1123 adult patients (median age 65 years; 61% males) with newly diagnosed acute myeloid leukemia (AML), not including acute promyelocytic leukemia, were seen at the Mayo Clinic. Treatment included intensive (n = 766) or lower intensity (n = 144) chemotherapy or supportive care (n = 213), with respective median survivals of 22, 9, and 2 months (p < 0.01). Intensive chemotherapy resulted in complete remission (CR) and CR with incomplete count recovery (CRi) rates of 44 and 33%, respectively, with no difference in survival outcome between the two (p = 0.4). Allogeneic hematopoietic stem cell transplant (AHSCT) was documented in 259 patients and provided the best survival rate (median 55 months; p < 0.01). After a median follow-up of 13 months, 841 (75%) deaths were recorded. Multivariate analysis identified age >60 years (HR 2.2, 1.9–2.6), adverse karyotype (HR 2.9, 1.9–4.9), intermediate-risk karyotype (HR 1.6, 1.02–2.6), post-myeloproliferative neoplasm AML (HR 1.9, 1.5–2.4), and other secondary AML (HR 1.3 (1.1–1.6) as risk factors for shortened survival. These risk factors retained their significance after inclusion of FLT3/NPM1 mutational status in 392 informative cases: FLT3+NPM1− (HR 2.8, 1.4–5.6), FLT3+/NPM+ (HR 2.6 (1.3–5.2), and FLT3−NPM1− (HR 1.8, 1.0–3.0). [ABSTRACT FROM AUTHOR]

Introduction: Obesity is a worldwide problem that is related to cardiac disease, thrombosis and cancer. However, little is known about the impact of obesity on the outcomes of adult acute lymphoblastic leukemia (ALL) patients. Methods: We retrospectively evaluated a cohort of 154 newly diagnosed adult ALL patients between 1994 and 2011 at Mayo Clinic (Rochester). According to the World Health Organization (WHO) international BMI classification, patients were stratified as underweight, normal weight, overweight, and obese. For some analyses, patients were also stratified according to a two-sided non-obese or obese classification. Results: The median follow-up time was 8.37 years. Obese patients were more likely to be women (p=0.024) and ≥ 60 years old (p=0.003). Five-year mortality rates were higher in obese patients than non-obese [HR 95% CI: 1.60 (1.03– 2.50) p=0.035]. This was also the case in subgroup analysis among T-cell patients although the number of patients was small [HR 95% CI: 5.42 (1.84– 15.98) p< 0.001]. There was no difference in mortality among the B-cell patients. After adjusting for baseline variables, the difference in mortality remained in several models. There was no difference in EFS or cumulative incidence of relapse rates between obese and non-obese patients among the overall population. Discussion: In conclusion, our study suggests that adult ALL patients with obesity have lower survival rates, especially in T-cell ALL. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal photopheresis (ECP) is an immunomodulatory cellular therapy which has been shown to induce a tolerogenic state in patients with acute and chronic graft-vs-host disease. ECOG-ACRIN explored the activity of ECP as a part of a reduced intensity conditioning regimen in two multicenter trials in patients with MDS (E1902) and lymphomas (E1402). While both studies closed before completing accrual, we report results in 23 patients (17 MDS and 6 lymphoma).Study Design and Methods: Patients received 2 days of ECP followed by pentostatin 4 mg/m2 /day for two consecutive days, followed by 600 cGy of total body irradiation prior to stem cell infusion. Immunosuppression for aGVHD was infusional cyclosporine A or tacrolimus and methotrexate on day +1, +3, with mycophenolate mofetil starting on day 100 for chronic GVHD prophylaxis.Results: All patients engrafted, with median time to neutrophil and platelet engraftment of 15-18 days and 10-18 days respectively. Grade 3 or 4 aGVHD occurred in 13% and chronic extensive GVHD in 30%.Conclusions: These studies demonstrate that ECP/pentostatin/TBI is well tolerated and associated with adequate engraftment of neutrophils and platelets in patients with lymphomas and MDS. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of pathologic immune activation in children that is increasingly being recognized in adults. Efficacy data for the HLH-04 protocol in adults is lacking. This study retrospectively analyzed 31 adult patients, median age 46 years, who received HLH-04 from 1/1/2004 to 5/1/2018. HLH etiology included malignancy (n = 9), autoimmune (n = 8), infection (n = 8), and idiopathic (n = 6). Eighteen patients were evaluable for response at week 4 with 7 having no response, 11 reaching partial response, and 0 reaching complete response (CR). Six patients eventually achieved CR at a median 195 days. The 1-year overall survival (OS) was 35% and median OS was 3.2 months. Univariate analysis showed shorter survival for hemoglobin <9 g/dL (HR 4.29, p = 0.003), platelets <100 × 109/L (HR 4.06, p = 0.027), ANC <1 × 109/L (HR 5.24, p = 0.001), and total bilirubin >1.2 mg/dL (HR 3.30, p = 0.022). Outcomes of adults treated with HLH-04 remain dismal and newer treatment modalities are needed. [ABSTRACT FROM AUTHOR]

Factors predicting allogeneic hematopoietic cell transplantation (HCT) outcomes in myelofibrosis in the early post-HCT period have not been defined thus far. We attempt to study such factors that can help identify patients at a higher risk of relapse or death. This retrospective study included 79 patients who underwent first HCT for myelofibrosis at three centers between 2005 and 2016. Univariate analysis showed that red blood cell (RBC) transfusion dependence (HR 9.02, 95% CI 4.0–20.35), platelet transfusion dependence (HR 8.17, 95%CI 3.83–17.37), 100% donor chimerism in CD33 + cells (HR 0.21, 95%CI 0.07–0.62), unfavorable molecular status (HR 4.41, 95%CI 1.87–10.39), normal spleen size (HR 0.42, 95%CI 0.19–0.94), grade ≥ 2 bone marrow fibrosis (vs. grade ≤ 1; HR 2.7, 95%CI 1.1–6.93) and poor graft function (HR 2.6, 95%CI 1.22–5.53) at day +100 were statistically significantly associated with relapse-free survival (RFS). RBC transfusion dependence and unfavorable molecular status were also statistically significant in the multivariate analysis. Patients in whom both of these factors were present had a significantly worse RFS when compared to those with one or none. While limited by a small sample size, we demonstrate the significance of transfusion dependence and molecular status at day +100 in predicting outcomes. [ABSTRACT FROM AUTHOR]

Clinical trials and treatment guidelines for myelodysplastic syndrome depend on several prognostic scoring systems to stratify patients by risk. These include different variables: the degree of cytopenia, percentage of bone marrow blasts, and cytogenetics. Little is known about the impact of bone marrow blasts in patients with adverse cytogenetics. In this retrospective study, we analyzed 536 patients with high-grade myelodysplastic syndrome to examine the differences in survival for patients with different percentages of bone marrow blasts. The median overall survival in patients with ≥ 5% marrow blasts was not statistically different from that for patients with < 5% marrow blasts; however, the former group had a higher risk of progression to acute myeloid leukemia (p < 0.001). Therefore, cytogenetics is the most important factor in our prognostic tools to determine survival outcomes for patients with myelodysplastic syndrome, and patients with high-risk disease have poor prognosis irrespective of their marrow blasts percentage. [ABSTRACT FROM AUTHOR]

Summary: Tumour lysis syndrome (TLS) is a significant complication of haematologic malignancies and their management. The syndrome consists of laboratory abnormalities either alone (laboratory TLS) or with clinical sequelae including renal failure, seizures, and arrhythmias (clinical TLS). Clinical TLS is a predictor for worse overall morbidity and mortality in cancer patients, but can be prevented. Thus, accurate prognostication is critical to appropriate management of patients at risk for TLS, and incorporates both disease factors (tumour type and burden) and patient factors (baseline renal insufficiency or hyperuricaemia). Strategies to prevent TLS include hydration and allopurinol in low‐ and intermediate‐risk patients and rasburicase in high‐risk patients. [ABSTRACT FROM AUTHOR]

The D-index assesses neutropenia dynamics. Prolonged neutropenia is a major risk for invasive fungal infection (IFI); we hypothesized that D-index is predictive of IFI risk. We retrospectively reviewed 789 adults who underwent allogeneic hematopoietic transplant (HSCT) from 1/1/2005 to 9/30/2015. Medical records were reviewed from transplant (D0) through Day 100. The D-index was calculated as area over the neutrophil curve until engraftment. 714 patients were included for analysis. Sixteen (2%) developed probable (11) or proven (5) IFI. Median time to IFI was 40 days (range 8-98) after HSCT. Groups with and without IFI did not differ significantly in duration of mild or profound neutropenia. Median D-index of those with IFI was 4293 days neutrophil/µl compared to 3590 days neutrophil/µl for those without IFI (P = 0.17). Patients who were neutropenic on D0 showed higher rates of IFI than those who were not (10/123 [8%] vs 6/591 [1%]; P < 0.001). Only 2% developed IFI, likely due to mold-active antifungal prophylaxis. The D-index was not significantly higher in those with IFI. Duration of profound neutropenia and neutropenia at D0 may be better markers for IFI among HSCT recipients during the first 30 and 100 days after transplant. [ABSTRACT FROM AUTHOR]

Background: Recipients of hematopoietic stem cell transplantation (HSCT) are among the highest consumers of allogeneic red blood cell (RBC) and platelet (PLT) components. The impact of patient blood management (PBM) efforts on HSCT recipients is poorly understood.Study Design and Methods: This observational study assessed changes in blood product use and patient-centered outcomes before and after implementing a multidisciplinary PBM program for patients undergoing HSCT at a large academic medical center. The pre-PBM cohort was treated from January 1 through September 31, 2013; the post-PBM cohort was treated from January 1 through September 31, 2015.Results: We identified 708 patients; 284 of 352 (80.7%) in the pre-PBM group and 225 of 356 (63.2%) in the post-PBM group received allogeneic RBCs (p < 0.001). Median (interquartile range [IQR]) RBC volumes were higher before PBM than after PBM (3 [2-4] units vs. 2 [1-4] units; p = 0.004). A total of 259 of 284 pre-PBM patients (91.2%) and 57 of 225 (25.3%) post-PBM patients received RBC transfusions when hemoglobin levels were more than 7 g/dL (p < 0.001). The median (IQR) PLT transfusion quantities was 3 (2-5) units for pre-PBM patients and 2 (1-4) units for post-PBM patients (p < 0.001). For patients with PLT counts of more than 10 × 109 /L, a total of 1219 PLT units (73.4%) were transfused before PBM and 691 units (48.8%) were transfused after PBM (p < 0.001). Estimated transfusion expenditures were reduced by $617,152 (18.3%). We noted no differences in clinical outcomes or transfusion-related adverse events.Conclusion: Patient blood management implementation for HSCT recipients was associated with marked reductions in allogeneic RBC and PLT transfusions and decreased transfusion-related costs with no detrimental impact on clinical outcomes. [ABSTRACT FROM AUTHOR]

Poor outcomes in elderly acute lymphoblastic leukemia (ALL) are well recognized, but the contributors are ill-defined. We characterized 124 patients ≥60 years old at our institution. The majority (n = 102, 82%) were treated with intensive chemotherapy. Of these, 8/102 (8%) died within the first 100 days; 92/102 (90%) achieved complete remission (CR/CRi). Only 31/124 (25%) patients underwent allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) for the entire cohort was 19.8 months. In a multivariate analysis, ECOG performance status ≥2, high white blood cell count, and high lactate dehydrogenase (at time of diagnosis) negatively influenced OS (p<.01). In a subgroup analysis of the intensive treatment group, BCR-ABL1+ patients had markedly better OS (hazard ratio 0.3, 95% CI 0.1–0.7; p<.01). In summary, despite few early deaths and a high CR/CRi rate, elderly ALL continues to have a poor prognosis, underscoring the need for more effective therapies. [ABSTRACT FROM AUTHOR]

Trabectedin is an FDA-approved DNA minor groove binder that has activity against translocation-associated sarcomas. Lurbinectedin is a next-generation minor groove binder with preclinical activity against myeloid leukemia cells. A dose-finding phase 1 clinical trial was performed in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with further assessment of safety and tolerability. Forty-two patients with relapsed/refractory AML/MDS received lurbinectedin administered as a 1-hour intravenous infusion in a 3 + 3 study design. Two dosing schedules were used: 3.5, 5, 7, or 6 mg on days 1 and 8 or 2, 3, 1, or 1.5 mg for 3 consecutive days on days 1 to 3. Three patients experienced dose-limiting toxicities of rhabdomyolysis (grade 4), hyperbilirubinemia (grade 3), and oral herpes (grade 3) with the day 1 and 8 schedule. Otherwise, adverse events mainly consisted of gastrointestinal manifestations (n = 11), febrile neutropenia/infections (n = 4), pulmonary toxicity (n = 2), and renal failure (n = 2). The most common laboratory abnormalities observed were an increase in creatinine (93%) and anemia, neutropenia, and thrombocytopenia (100%). Overall, 33 of 42 patients (79%) had reduction in blasts in peripheral blood or bone marrow. One patient achieved a partial response and 2 patients a morphologic leukemia-free state. Most (n = 30, 71%) were discontinued due to progressive disease. Early deaths occurred from disease-related causes that were not attributable to lurbinectedin. Four patients with a chromosome 11q21-23 abnormality had significantly greater bone marrow blast reduction than those without such abnormality, with decrease of 31 ± 14% (n = 4) vs 8 ± 8% (n = 16), respectively (P = .04). Overall, lurbinectedin was safe and tolerated using the schedules and dose levels tested. While no sustained remissions were observed, single-agent lurbinectedin was transiently leukemia suppressive for some patients. [ABSTRACT FROM AUTHOR]

Lenalidomide is known to increase the risk of venous thromboembolism in patients with hematologic malignancies. The role of antithrombotic prophylaxis in patients receiving lenalidomide is well established in multiple myeloma. However, when used in patients with a myelodysplastic syndrome (MDS)-in particular, del(5q) patients-the risk of venous thromboembolism and the need for anticoagulation are unknown. We performed a retrospective for MDS patients with 5q deletion. The total number of patients was 64, and 24 (38%) were treated with lenalidomide. Of those who received lenalidomide, venous thrombotic events (VTE) occurred in 4 (17%). All events occurred after 1 year of lenalidomide therapy. Although limited by the cohort size, concurrent erythropoietin-stimulating agents (ESAs) were not associated with increased thrombotic events, and the diagnosis of VTE did not affect survival. Our data suggest an increased incidence of VTE with prolonged lenalidomide treatment, mainly if MDS responds to this therapy. [ABSTRACT FROM AUTHOR]