Prognostic significance of preoperative absolute peripheral monocyte count in esophageal squamous cell carcinoma

The objective of this study was to investigate the prognostic value of peripheral blood monocytes in esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy. Records from 218 consecutive patients with histologically diagnosed ESCC who underwent esophagectomy at Qilu Hospital of Shandong University from January 2007 to December 2008 were retrospectively reviewed. The median disease‐free survival (DFS) of this cohort was 29.0 months, and the 5‐year DFS rate was 34.4%. The median overall survival (OS) was 35.0 months, and the 5‐year OS rate was 37.6%. The cut‐off value of 0.42 × 10⁹/L for the absolute monocyte count (AMC) was chosen as optimal to discriminate between survival and death by applying receiver operating curve analysis. There were 131 patients (60.1%) who had high AMC (≥0.42 × 10⁹/L) preoperatively. We found that AMC was significantly associated with gender, tumor location, and platelet count. Kaplan–Meier survival analysis of patients with high preoperative AMC had a significant worse prognosis for DFS (high vs. low: 27.5% vs. 39.0%, P = 0.015) and OS (high vs. low: 31.1% vs. 44.8%, P = 0.009) than those with low preoperative AMC. In a multivariate analysis, preoperative AMC was an independent prognostic factor for DFS (P = 0.025, hazard ratio [HR]: 1.469, 95% confidence interval [CI]: 1.050–2.054) and OS (P = 0.015, HR: 1.547, 95% CI: 1.088–2.200). In addition, among 140 patients without both preoperative and postoperative therapy, significantly worse OS (P = 0.012) and marginally reduced DFS (P = 0.079) were found in the high AMC cohort versus the low AMC cohort. A higher preoperative absolute peripheral monocyte count can be considered as a useful prognostic marker of ESCC patients who underwent esophagectomy.     

Absolute lymphocyte count at the time of first relapse predicts survival in patients with diffuse large B‐cell lymphoma

Peripheral blood absolute lymphocyte count (ALC) is a survival prognostic factor in hematological malignancies. No reports have addressed whether ALC at the time of first relapse (ALC‐R) predicts survival. Thus, we assessed the prognostic significance of ALC‐R in diffuse large B‐cell lymphoma (DLBCL). Patients were required to have been diagnosed with first relapsed DLBCL, have ALC‐R values, and to be followed at Mayo Clinic, Rochester. From Feb 1987 until March 2006, 97 first relapsed DLBCL patients qualified for the study. The overall survival (OS) and progression‐free survival (PFS) were measured from the time of first relapse. The value of ALC‐R ≥ 1.0 × 10⁹/L was used for the analysis. Both groups (ALC‐R ≥ 1 or < 1 × 10⁹/L) were balanced for the international prognostic index at relapse (IPI‐R) (P = 0.3), and for autologous stem cell transplantation (P = 0.4). Superior OS and PFS were observed with an ALC‐R ≥ 1.0 × 10⁹/L (N = 60) versus ALC‐R < 1.0 × 10⁹/L (N = 37) [median OS: 28.7 months, 5 years OS rates of 39% versus median OS: 10.2 months, 5 years OS rates of 14%, P < 0.002; and median PFS: 14.8 months, 5 years PFS rates of 21% versus median PFS: 6.5 months, 5 years PFS rates of 8%, P < 0.004, respectively]. ALC‐R was an independent prognostic factor for OS [RR = 0.4, P < 0.01] and PFS [RR = 0.5, P < 0.005]. ALC‐R predicts survival suggesting that host immunity is an important variable predicting survival in first relapsed DLBCL. Am. J. Hematol. 2009. © 2008 Wiley‐Liss, Inc.     

Decreased survival and increased rate of fibrotic progression in essential thrombocythemia chronicled after the FDA approval date of anagrelide

First-line cytoreductive drug of choice in high risk essential thrombocythemia (ET) is currently hydroxyurea, a practice based on the results of a randomized study; second-line drugs of choice include pegylated interferon-α, busulfan and anagrelide. Anagrelide clinical trials were pioneered by the late Murray N. Silverstein (1928-1998) of the Mayo Clinic whose studies led to FDA approval in March 1997. The current study represents a retrospective examination of the potential impact of anagrelide therapy on survival and disease complications in ET. 1076 patients with ET were considered (median age 58 years; females 63%); risk distribution, according to the international prognostic score for ET (IPSET), was 28% high, 42% intermediate, and 30% low. Overall (OS), myelofibrosis-free (MFFS) and thrombosis-free survival data were compared for ET patients diagnosed before and after the 1997 FDA approval date for anagrelide; a significant difference was apparent in OS (P = .006; HR 1.4, 95% CI 1.1-1.7) and MFFS (P < .001; HR 4.2, 95% CI 2.7-6.5), in favor of patients diagnosed prior to 1997; the difference was sustained during multivariable analysis that included IPSET. Similarly stratified survival data in polycythemia vera (n = 665) and primary myelofibrosis (n = 1282) showed no similar impact on survival (P = .3 and .17, respectively). The current study represents a retrospective analysis and suggests significantly decreased OS and MFFS in ET patients diagnosed after the FDA approval date of anagrelide. Whether or not anagrelide therapy was to blame for the worsening of OS and MFFS over time cannot be assumed and requires validation in a prospective study.     

Clinical significance of regulatory T cells in patients with myelodysplastic syndrome

Objective: Foxp3⁺ regulatory T cells (Tregs) play a central role in maintaining immune tolerance. Their expansion in malignant diseases leads to the suppression of host anti‐tumour responses. In this study, we evaluated the clinical significance of Tregs in patients with myelodysplastic syndrome (MDS). Patients and Methods: We analysed the number of CD4⁺ CD25⁺ Foxp3⁺ Tregs using three‐colour flow cytometry in the peripheral blood of 26 patients with MDS classified according to the World Health Organization classification method into four cases of refractory anaemia and refractory anaemia with ringed sideroblasts (RA/RARS), 15 cases of refractory cytopenia with multilineage dysplasia (RCMD), three cases of refractory anaemia with excess blast‐1 (RAEB‐1) and four cases of refractory anaemia with excess blast‐2 (RAEB‐2). Eighteen healthy volunteers were included as the control group. Results: The mean absolute numbers of Tregs in the RA/RARS group (0.06 × 10⁹/L; 95% CI, 0.02–0.10 × 10⁹/L) and RAEB group (0.06 × 10⁹/L; 95% CI, 0.02–0.10 × 10⁹/L) were significantly higher than that of the control group (0.03 × 10⁹/L; 95% CI, 0.02–0.03 × 10⁹/L) (P < 0.05). However, in the RCMD group, there was no significant difference in the mean absolute number of Tregs (0.03 × 10⁹/L; 95% CI, 0.02–0.04 × 10⁹/L) compared with the control group. Regarding the mean level of the CD8/Foxp3 ratio, there were significant decreases in the RA/RARS group (2.8; 95% CI, 0.7–4.9; P < 0.01), RCMD group (3.4; 95% CI, 2.0–4.4; P < 0.001) and RAEB group (2.1; 95% CI, 1.7–2.5; P < 0.001) compared with the control group (6.1; 95% CI, 5.1–7.0). Conclusions: The expansion of natural CD4⁺ Tregs may contribute to the suppression of CD8 through the Th1‐mediated immune response in MDS. The low CD8/Foxp3 ratio is a characteristic feature in MDS. To determine whether the expansion of CD4⁺ Tregs contributes to the progression of MDS subtypes into more aggressive subtypes, more MDS cases and further follow‐up are required.     

Thrombosis and survival in essential thrombocythemia: A regional study of 1,144 patients

To identify prognostic factors affecting thrombosis‐free survival (TFS) and overall survival (OS), we report the experience of a Regional cooperative group in a real‐life cohort of 1,144 patients with essential thrombocythemia (ET) diagnosed from January 1979 to December 2010. There were 107 thrombotic events (9.4%) during follow‐up [60 (5.3%) arterial and 47 (4.1%) venous thromboses]. At univariate analysis, risk factors for a shorter TFS were: age >60 years (P < 0.0054, 95% CI 1.18–2.6), previous thrombosis (P < 0.0001, 95% CI 1.58–4.52) and the presence of at least one cardiovascular risk factor (P = 0.036, 95% CI 1.15–3.13). Patients with a previous thrombosis occurred ≥24 months before ET diagnosis had a shorter TFS compared to patients with a previous thrombosis occurred <24 months (P = 0.0029, 95% CI 1.5–6.1); furthermore, patients with previous thrombosis occurred <24 months did not show a shorter TFS compared with patients without previous thrombosis (P = 0.303, 95% CI 0.64–3.21). At multivariate analysis for TFS, only the occurrence of a previous thrombosis maintained its prognostic impact (P = 0.0004, 95% CI 1.48–3.79, RR 2.36). The 10‐year OS was 89.9% (95% CI 87.3–92.5): at multivariate analysis for OS, age >60 years (P < 0.0001), anemia (P < 0.0001), male gender (P = 0.0019), previous thromboses (P = 0.0344), and white blood cell >15 × 10⁹/l (P = 0.0370) were independent risk factors. Previous thrombotic events in ET patients are crucial for TFS but their importance seems related not to the occurrence per se but mainly to the interval between the event and the diagnosis. Am. J. Hematol. 89:542–546, 2014. © 2014 Wiley Periodicals, Inc.     

White blood cell count and mortality in patients with acute pulmonary embolism

Although associated with adverse outcomes in other cardiovascular diseases, the prognostic value of an elevated white blood cell (WBC) count, a marker of inflammation and hypercoagulability, is uncertain in patients with pulmonary embolism (PE). We therefore sought to assess the prognostic impact of the WBC in a large, state‐wide retrospective cohort of patients with PE. We evaluated 14,228 patient discharges with a primary diagnosis of PE from 186 hospitals in Pennsylvania. We used random‐intercept logistic regression to assess the independent association between WBC count levels at the time of presentation and mortality and hospital readmission within 30 days, adjusting for patient and hospital characteristics. Patients with an admission WBC count <5.0, 5.0–7.8, 7.9–9.8, 9.9–12.6, and >12.6 × 10⁹/L had a cumulative 30‐day mortality of 10.9%, 6.2%, 5.4%, 8.3%, and 16.3% (P < 0.001), and a readmission rate of 17.6%, 11.9%, 10.9%, 11.5%, and 15.0%, respectively (P < 0.001). Compared with patients with a WBC count 7.9–9.8 × 10⁹/L, adjusted odds of 30‐day mortality were significantly greater for patients with a WBC count <5.0 × 10⁹/L (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.14–2.03), 9.9–12.6 × 10⁹/L (OR 1.55, 95% CI 1.26–1.91), or >12.6 × 10⁹/L (OR 2.22, 95% CI 1.83–2.69), respectively. The adjusted odds of readmission were also significantly increased for patients with a WBC count <5.0 × 10⁹/L (OR 1.34, 95% CI 1.07–1.68) or >12.6 × 10⁹/L (OR 1.29, 95% CI 1.10–1.51). In patients presenting with PE, WBC count is an independent predictor of short‐term mortality and hospital readmission. Am. J. Hematol. 88:677–681, 2013. © 2013 Wiley Periodicals, Inc.     

Early lymphocyte recovery at 28 d post‐transplant is predictive of reduced risk of relapse in patients with acute myeloid leukemia transplanted with peripheral blood stem cell grafts

Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for acute myeloid leukemia (AML). Impact of lymphocyte recovery on post‐transplant outcomes has been suggested but reports are conflicting. We evaluated the impact of lymphocyte recovery at 28 d post‐HCT in 191 AML patients using peripheral blood stem cells as graft. Patients were divided into those with absolute lymphocyte count (ALC) ≥0.5 × 10⁹/L (n = 111, 58%; high ALC group) and those with ALC <0.5 × 10⁹/L (n = 80, 42%; low ALC group), at day 28 post‐transplant. With a median follow‐up of 49 months, overall survival (OS) was significantly improved in the high ALC group (59% at 3 yr) vs. patients with low ALC (40% at 3 yr, P = 0.03). Cumulative incidence of relapse (CIR) was significantly lower in the high ALC group (16% at 3 yr) vs. low ALC group (36% at 3 yr, P = 0.001). Multivariable analysis for CIR demonstrated high ALC group as an independent factor decreasing relapse risk (P = 0.03, HR = 0.49, 95% CI = 0.26–0.92). Multivariable analysis for OS and non‐relapse mortality did not demonstrate ALC ≥0.5 × 10⁹/L at 28 d post‐transplant to be predictive. We conclude that lymphocyte recovery with ALC ≥0.5 × 10⁹/L at day 28 post‐transplant is associated with less relapse in AML patients undergoing allogeneic peripheral blood HCT, but without survival benefit.     

A systemic inflammation response index (SIRI) correlates with survival and predicts oncological outcome for mFOLFIRINOX therapy in metastatic pancreatic cancer

ObjectivesSystemic inflammatory response and survival has not been evaluated as a predictive factor of chemotherapy in metastatic pancreatic cancer. The aim of this study was to evaluate the prognostic and predictive value of a baseline Systemic Inflammation Response Index (SIRI) in metastatic pancreatic cancer.MethodsRetrospective study of 164 metastatic pancreatic cancer patients. Associations between overall survival (OS), progression free survival (PFS), chemotherapy and SIRI were analyzed. SIRI is defined by neutrophil x monocyte/lymphocyte 10⁹/L.ResultsMedian age 66 years. 22 (13%) received mFOLFIRINOX, 59 (36%) gemcitabine + nab-paclitaxel, 40 (24%) gemcitabine, 13 (8%) other regimens and 30 (18%) had not received treatment. Patients with SIRI<2.3 × 10⁹/L showed a statistically significant improvement in OS compared to SIRI≥2.3 × 10⁹/L [16 months versus 4.8 months, Hazard Ratio (HR) 2.87, Confidence Interval (CI) 95% 2.02–4.07, p < 0.0001] that was confirmed in multivariate analysis. In addition, patients with SIRI<2.3 × 10⁹ showed a longer PFS (12 versus 6 months, HR 1.92, IC 95% 1.314–2.800, P = 0.001). Furthermore, we observed that patients with SIRI ≥2.3 × 10⁹/L were more likely to benefit from mFOLFIRINOX therapy. Patients with an elevated SIRI treated with mFOLFIRINOX versus gemcitabine plus nab-paclitaxel and gemcitabine showed a clinically and statistically significant difference in median OS of 17 months compared to 6 and 4 months respectively (p < 0.001). Conversely, the difference was not clinically significant in the SIRI<2.3 × 10⁹/L subgroup: 15.9 months versus 16.5 and 16, respectively.ConclusionAn elevated SIRI (≥2.3 × 10⁹/L) was an independent prognostic factor for patients with metastatic pancreatic cancer, warranting prospective evaluation.     

Impact of HIV on liver fibrosis in men with hepatitis C infection and haemophilia

Summary. Hepatitis C virus (HCV) is the major cause of liver disease in haemophilia. Few data exist on the proportion with liver fibrosis in this group after long‐term HCV and HIV co‐infection. We conducted a cross‐sectional multi‐centre study to determine the impact of HIV on the prevalence and risk factors for fibrosis in haemophilic men with chronic hepatitis C. Biopsies were independently scored by Ishak, Metavir and Knodell systems. Variables were tested for associations with fibrosis using logistic regression and receiver operating curves (ROC). Of 220 biopsied HCV(+) men, 23.6% had Metavir ≥F3 fibrosis, with higher mean Metavir fibrosis scores among HIV/HCV co‐infected than HCV mono‐infected, 1.6 vs. 1.3 (P = 0.044). Variables significantly associated with fibrosis included AST, ALT, APRI score (AST/ULN × 100/platelet × 10⁹/L), alpha‐fetoprotein (all P < 0.0001), platelets (P = 0.0003) and ferritin (P = 0.0008). In multiple logistic regression of serum markers, alpha‐fetoprotein, APRI and ALT were significantly associated with ≥F3 fibrosis [AUROC = 0.77 (95% CI 0.69, 0.86)]. Alpha‐fetoprotein, APRI and ferritin were significant in HIV(?) [AUROC = 0.82 (95% CI 0.72, 0.92)], and alpha‐fetoprotein and platelets in HIV(+) [AUROC = 0.77 (95% CI 0.65, 0.88]. In a multivariable model of demographic and clinical variables, transformed (natural logarithm) of alpha‐fetoprotein (P = 0.0003), age (P = 0.006) and HCV treatment (P = 0.027) were significantly associated with fibrosis. Nearly one‐fourth of haemophilic men have Metavir ≥3 fibrosis. The odds for developing fibrosis are increased in those with elevated alpha‐fetoprotein, increasing age and past HCV treatment.     

Prognostic indicators in primary plasma cell leukaemia: a multicentre retrospective study of 117 patients

We report a multicentre retrospective study that analysed clinical characteristics and outcomes in 117 patients with primary plasma cell leukaemia (pPCL) treated at the participating institutions between January 2006 and December 2016. The median age at the time of pPCL diagnosis was 61 years. Ninety‐eight patients were treated with novel agents, with an overall response rate of 78%. Fifty‐five patients (64%) patients underwent upfront autologous stem cell transplantation (ASCT). The median follow‐up time was 50 months (95% confidence interval [CI] 33; 76), with a median overall survival (OS) for the entire group of 23 months (95% CI 15; 34). The median OS time in patients who underwent upfront ASCT was 35 months (95% CI 24·3; 46) as compared to 13 months (95% CI 6·3; 35·8) in patients who did not receive ASCT (P = 0·001). Multivariate analyses identified age ≥60 years, platelet count ≤100 × 10⁹/l and peripheral blood plasma cell count ≥20 × 10⁹/l as independent predictors of worse survival. The median OS in patients with 0, 1 or 2–3 of these risk factors was 46, 27 and 12 months, respectively (P < 0·001). Our findings support the use of novel agents and ASCT as frontline treatment in patients with pPCL. The constructed prognostic score should be independently validated.     

Calreticulin variant stratified driver mutational status and prognosis in essential thrombocythemia

About 85% of patients with essential thrombocythemia (ET) harbor one of three driver mutations: JAK2, calreticulin (CALR), and MPL; the remaining ( ～15%) are wild type for all three mutations and are referred to as being “triple negative.” Furthermore, CALR mutations in ET are structurally classified as type 1/type 1‐like or type 2/type 2‐like variants. The objective of the current study was to examine the impact of CALR mutation variant stratified driver mutational status on overall (OS), myelofibrosis‐free (MFFS), thrombosis‐free, and leukemia‐free survival (LFS) in ET; 495 patients (median age 58 years; 61% females) with ET were fully annotated for the their driver mutational status: 321 (65%) harbored JAK2, 109 (22%) CALR, and 12 (2%) MPL mutations and 11% were triple‐negative. Among the 109 CALR‐mutated cases, 52% were classified as type 1/type 1‐like and 48% as type 2/type 2‐like. In univariate analysis, triple‐negative patients displayed the best and MPL mutated the worst OS (P = 0.007); however, the difference in OS was no longer apparent on multivariable analysis that included age and sex as covariates (P = 0.5). LFS was also similar among the different mutational groups (P = 0.6) whereas MFFS was significantly shorter in MPL‐mutated patients on both univariate and multivariable analyses (age‐adjusted P = 0.02; HR 7.9, 95% CI 2.0–31.5). Also in multivariable analysis that included thrombosis history, age, and cardiovascular risk factors, the presence of JAK2 or MPL mutations was independently associated with higher risk of thrombosis (P = 0.02; HR 1.9, 95% CI 1.1–3.4). In conclusion, driver mutational status in ET does not appear to influence overall or LFS, even after CALR variant stratification. However, the presence of MPL mutations might be associated with a higher risk of fibrotic transformation and the presence of JAK2/MPL mutations with higher risk of thrombosis. Am. J. Hematol. 91:503–506, 2016. © 2016 Wiley Periodicals, Inc.     

Risk factors and a prognostic model for postsplenectomy survival in myelofibrosis

Palliative treatment in myelofibrosis (MF) includes transfusion support, JAK2 inhibitors, involved field radiotherapy and splenectomy. To assist in selecting patients who are likely to benefit from splenectomy, we looked into risk factors for postsplenectomy survival, in 120 consecutive cases (median age 66 years); at the time of splenectomy, 61% displayed red cell transfusion need, 49% platelet count <100 × 10(9)/L, 25% leukocyte count >25 × 10(9)/L, 60% constitutional symptoms and 13% circulating blasts ≥5%; dynamic international prognostic scoring system risk categories were 21% high, 55% intermediate‐2, 21% intermediate‐1 and 3% low. Among informative cases, karyotype was abnormal in 60% and driver mutational status was JAK2 75%, CALR 15%, MPL 4% and triple‐negative 6%. At median follow‐up of 1.3 years, from time of splenectomy, 95 (79%) deaths and 30 (25%) leukemic transformations were recorded. Median postsplenectomy survival was 1.5 years; in multivariable analysis, survival was adversely affected by age >65 years, transfusion need, leukocyte count >25 × 10(9)/L and circulating blasts ≥5%; these variables were subsequently used to devise an HR‐weighted scoring system with high (3‐4 risk factors), intermediate (2 risk factors) and low (0‐1 risk factors) risk categories; the corresponding postsplenectomy median survivals were 0.3 (HR 5.9, 95% CI 3.2‐11.0), 1.3 (HR 2.9, 95% CI 1.8‐4.6) and 2.9 years. Postsplenectomy survival was not affected by driver mutational status or occurrence of leukemic transformation. Leukemia‐free survival was predicted by very high risk karyotype. The observations from the current study might help identify appropriate candidates for splenectomy in MF.     

Minimal residual disease before and after transplantation for childhood acute lymphoblastic leukaemia: is there any room for intervention?

Eighty‐two children and adolescents who underwent allogeneic transplantation for acute lymphoblastic leukaemia in remission (period 2001–2011, median follow‐up 4·9 years) had been assessed for minimal residual disease (MRD) by real‐time quantitative polymerase chain reaction before and at 1, 3, 6, 9 and 12 months after transplantation. Five‐year event‐free survival (EFS) and cumulative incidence of relapse were 77·7% [standard error (SE) 5·7] and 11·4% (SE 4·4), respectively, for patients with pre‐transplant MRD <1 × 10^?4 (68%), versus 30·8% (SE 9·1; P < 0·001) and 61·5% (SE 9·5; P < 0·001), respectively, for those with MRD ≥1 × 10^?4 (32%). Pre‐transplant MRD ≥1 × 10^?4 was associated with a 9·2‐fold risk of relapse [95% confidence interval (CI) 3·54–23·88; P < 0·001] compared with patients with MRD <1 × 10^?4. Patients who received additional chemotherapy pre‐transplant to reduce MRD had a fivefold reduction of risk of failure (hazard ratio 0·19, CI 0·05–0·70, P = 0·01). Patients who experienced MRD positivity post‐transplant did not necessarily relapse (5‐year EFS 40·3%, SE 9·3), but had a 2·5‐fold risk of failure (CI 1·05–5·75; P = 0·04) if any MRD was detected in the first 100 d, which increased to 7·8‐fold (CI 2·2–27·78; P = 0·002) if detected after 6 months. Anticipated immunosuppression‐tapering according to MRD may have improved outcome, nevertheless all patients with post‐transplant MRD ≥1 × 10^?3 ultimately relapsed, regardless of immunosuppression discontinuation or donor‐lymphocyte‐infusion. In conclusion, MRD before transplantation had the strongest impact on relapse and MRD positivity after transplantation, mostly if detected early and at low levels, did not necessarily imply relapse. Additional intensified chemotherapy and modulation of immunosuppression may reduce relapse risk and improve ultimate outcome.     

Interactions and relevance of blast percentage and treatment strategy among younger and older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)

Acute myeloid leukemia (AML) is defined as ≥20% myeloblasts, representing a change from original guidelines where ≤30% blasts were considered as myelodysplastic syndromes (MDS), and 20–29% blasts classified as refractory anemia with excess blasts in transformation (RAEB‐T). Whether the diagnostic bone marrow blast percentage has current value with regards to patient prognostication or identification of optimal treatment strategies is unclear. We retrospectively studied 1652 treatment‐naïve adults with MDS or AML and ≥10% blasts from January 2000 to April 2014. Patients with 20–29% blasts were more similar to MDS patients in terms of advanced age, increased frequency of poor‐risk cytogenetics, lower WBC count, and less frequent NPM1 and FLT3‐ITD mutations. Median overall survival of MDS and RAEB‐T were similar, 16.0 and 16.0 months, compared to 13.5 months for AML with ≥30% blasts (P = 0.045). Multivariate analysis showed inferior survival with increased age (HR 1.81 age 60–69, HR 2.68 age ≥70, P < 0.0005); poor‐risk cytogenetics (HR 2.25, P < 0.0005); therapy‐related disease (HR 1.44, P < 0.0005); and markers of proliferative disease including WBC ≥25 × 10⁹/L (HR 1.35, P = 0.0003), elevated LDH count (HR 1.24, P = 0.0015), and peripheral blasts (HR 1.25, P = 0.004). Among younger patients (≤60 years), intensive AML‐type therapy resulted in similar outcomes regardless of blast percentage, suggesting this to be optimal therapy in this context. Among older patients (≥70 years), patients with 20–29% blasts had similar outcomes to patients with <20% blasts, and better than those with ≥30% blasts. In addition, among older patients, epigenetic therapy provided at least equivalent outcome to intensive chemotherapy. Am. J. Hematol. 91:227–232, 2016. © 2015 Wiley Periodicals, Inc.     

Host immunity affects survival in myelodysplastic syndromes: Independent prognostic value of the absolute lymphocyte count

The prognostic significance of the peripheral blood absolute lymphocyte count (ALC) has been carefully examined in lymphoid malignancies, but the importance of the baseline ALC in chronic myeloid neoplasms is less clear. In a recent analysis of myelodysplastic syndromes (MDS) associated with deletion of chromosome 5q, we observed that an ALC < 1.2× 10⁹ cells/L at diagnosis is independently associated with poorer survival. Clinicopathological data from 503 patients with non‐del(5q) MDS evaluated at Mayo Clinic between 1996 and 2007 were reviewed to determine the prognostic impact of ALC at diagnosis in non‐del(5q) MDS. Patients with MDS and an ALC at diagnosis ≥1.2× 10⁹ (N = 248) experienced a superior overall survival (OS) compared with patients with an ALC < 1.2× 10⁹/L (N = 255, median OS of 26.6 months versus 18.5 months, P < 0.001, respectively). ALC at diagnosis was an independent predictor for OS when compared with the International Prognostic Scoring System and the WHO‐based Prognostic Scoring System. This study suggests that ALC at diagnosis is a prognostic factor for OS in MDS, and argues in favor of further studies to assess the role of host immunity in MDS clinical outcomes. Am. J. Hematol. 2010. © 2009 Wiley‐Liss, Inc.     

Impact of spleen size and splenectomy on outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis: A retrospective analysis by the chronic malignancies working party on behalf of European society for blood and marrow transplantation (EBMT)

The role of spleen size and splenectomy for the prediction of post‐allogeneic hematopoietic stem cell transplant (allo‐HCT) outcome in myelofibrosis remains under debate. In EBMT registry, we identified a cohort of 1195 myelofibrosis patients transplanted between 2000‐2017 after either fludarabine‐busulfan or fludarabine‐melphalan regimens. Overall, splenectomy was performed in 202 (16.9%) patients and its use decreased over time (28.3% in 2000‐2009 vs 14.1% in 2010‐2017 period). By multivariate analysis, splenectomy was associated with less NRM (HR 0.64, 95% CI 0.44‐0.93, P = .018) but increased risk of relapse (HR 1.43, 95% CI 1.01‐2.02, P = .042), with no significant impact on OS (HR 0.86, 95% CI 0.67‐1.12, P = .274). However, in subset analysis comparing the impact of splenectomy vs specific spleen sizes, for patients with progressive disease, an improved survival was seen in splenectomised subjects compared to those patients with a palpable spleen length ≥ 15 cm (HR 0.44, 95% CI 0.28‐0.69, P < .001), caused by a significant reduction in NRM (HR 0.26, 95% CI 0.14‐0.49, P < .001), without significantly increased relapse risk (HR 1.47, 95% CI 0.87‐2.49, P = .147). Overall, despite the possible biases typical of retrospective cohorts, this study highlights the potential detrimental effect of massive splenomegaly in transplant outcome and supports the role of splenectomy for myelofibrosis patients with progressive disease and large splenomegaly.     

Association between baseline body mass index and overall survival among patients over age 60 with acute myeloid leukemia

Acute myeloid leukemia (AML) is more common and more lethal among patients over the age of 60. Increased body mass index (BMI) has been associated with a higher incidence of various malignancies, including AML. We sought to determine whether patient BMI at the time of AML diagnosis is related to overall survival (OS) among elderly patients. We identified 97 patients with AML diagnosed after the age of 60 and treated with cytarabine‐based induction chemotherapy. The median age was 68 years (range 60–87); 52% of patients were male, and our study population was predominantly white (89% of patients). The median OS for all patients was 316 days (95% CI 246–459). The hazard ratio for mortality was increased among patients with a BMI < 25 compared to BMI ≥ 30 (HR 2.14, P = 0.009, 95% CI 1.21–3.77), as well as with older age (HR 1.76, P = 0.015, 95% CI 1.12–2.79) and with secondary versus de novo disease (HR 1.95, P = 0.006, 95% CI 1.21–3.14). After multivariable analysis, we did not find a significant association between OS and other potential confounders such as coronary artery disease or diabetes among these patients. We conclude that increased BMI was independently associated with improved OS among older AML patients at our institution. Am. J. Hematol. 88:642–646, 2013. © 2013 Wiley Periodicals, Inc.     

Does the site of platelet sequestration predict the response to splenectomy in adult patients with immune thrombocytopenic purpura?

Splenectomy is the only potentially curative treatment for chronic immune thrombocytopenic purpura (ITP) in adults. However, one-third of the patients relapse without predictive factors identified. We evaluate the predictive value of the site of platelet sequestration on the response to splenectomy in patients with ITP. Eighty-two consecutive patients with ITP treated by splenectomy between 1992 and 2013 were retrospectively reviewed. Platelet sequestration site was studied by ¹¹¹Indium-oxinate-labeled platelets in 93% of patients. Response to splenectomy was defined at last follow-up as: complete response (CR) for platelet count (PC) ≥100?×?10⁹/L, response (R) for PC≥30?×?10⁹/L and <100?×?10⁹/L with absence of bleeding, no response (NR) for PC<30?×?10³/L or significant bleeding. Laparoscopic splenectomy was performed in 81 patients (conversion rate of 16%), and open approach in one patient. Median follow-up was 57 months (range, 1–235). Platelet sequestration study was performed in 93% of patients: 50 patients (61%) exhibited splenic sequestration, 9 (11%) hepatic sequestration and 14 patients (17%) mixed sequestration. CR was obtained in 72% of patients, R in 25% and NR in 4% (two with splenic sequestration, one with hepatic sequestration). Preoperative PC, age at diagnosis, hepatic sequestration and male gender were significant for predicting CR in univariate analysis, but only age (HR?=?1.025 by one-year increase, 95% CI [1.004–1.047], p?=?0.020) and pre-operative PC (HR?=?0.112 for?>?100 versus <=100, 95% CI [0.025–0.493], p?=?0.004) were significant predictors of recurrence-free survival in multivariate analysis. Response to splenectomy was independent of the site of platelet sequestration in patients with ITP. Pre-operative platelet sequestration study in these patients cannot be recommended.     

Major surgery seems not to influence HIV disease progression in haemophilia patients

The influence of major surgery on HIV disease progression and decline in CD4⁺ cell count was evaluated in 23 seropositive haemophilia patients. 24 HIV-infected patients served as non-operated controls. In addition, 32 age-matched seronegative subjects were included. The follow-up time was up to 5 years. During the course of the study, eight of the operated (35%) and 11 of the non-operated (48%) subjects developed HIV-related symptoms (P = 0.267). The relative risk for developing HIV-related symptoms after surgery was 0.60 (95% CI 0.25; 1.48). A significant decline in CD4⁺ cell counts was observed in both the surgery (4.0 × 10⁶/l/month, 95% CI 2.0; 6.0 × 10⁶, P = 0.001) and the non-surgery (4.0 × 10⁶/l/month, 95% CI 2.0; 6.0 × 10⁶, P = 0.004) seropositive subgroup, but no difference between the two subgroups was seen (P = 0.793). HIV (6.0 × 10⁶/l/month, 95% CI 2.1; 9.9 × 10⁶, P = 0.0005) but not surgery (?1.0 × 10⁶/l/month, 95% CI ?3.0; 0.96 × 10⁶, P = 0.647) was an independent predictor for the decline in CD34⁺ cell count. No interaction effect was observed between HIV infection and surgery (P = 0.361). The annual amount of factor concentrate used for regular replacement therapy did not influence the decline in CD4⁺ cell count (P = 0.492). We conclude that major surgery may be considered in symptom-free HIV-seropositive haemophilia patients, with CD4⁺ cell counts 0.20 × 10⁹/l under similar premises as for seronegative subjects.     

Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme

The efficacy of azacitidine in the treatment of high‐risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20–30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors for response, we analysed a cohort of 90 MDS, CMML and AML patients who have been treated in a Dutch compassionate named patient programme. Patients received azacitidine for a median of five cycles (range 1–19). The overall response rate (complete/partial/haematological improvement) was 57% in low risk MDS, 53% in high risk MDS, 50% in CMML, and 39% in AML patients. Median overall survival (OS) was 13·0 (9·8–16·2) months. Multivariate analysis confirmed circulating blasts [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·24–0·99; P = 0·05] and poor risk cytogenetics (HR 0·45, 95% CI 0·22–0·91; P = 0·03) as independent predictors for OS. Interestingly, this analysis also identified platelet doubling after the first cycle of azacitidine as a simple and independent positive predictor for OS (HR 5·4, 95% CI 0·73–39·9; P = 0·10). In conclusion, routine administration of azacitidine to patients with variable risk groups of MDS, CMML and AML is feasible, and subgroups with distinct efficacy of azacitidine treatment can be identified.