CAR19 monitoring by peripheral blood immunophenotyping reveals histology-specific expansion and toxicity.

ABSTRACT: Chimeric antigen receptor (CAR) T cells directed against CD19 (CAR19) are a revolutionary treatment for B-cell lymphomas (BCLs). CAR19 cell expansion is necessary for CAR19 function but is also associated with toxicity. To define the impact of CAR19 expansion on patient outcomes, we prospectively followed a cohort of 236 patients treated with CAR19 (brexucabtagene autoleucel or axicabtagene ciloleucel) for mantle cell lymphoma (MCL), follicular lymphoma, and large BCL (LBCL) over the course of 5 years and obtained CAR19 expansion data using peripheral blood immunophenotyping for 188 of these patients. CAR19 expansion was higher in patients with MCL than other lymphoma histologic subtypes. Notably, patients with MCL had increased toxicity and required fourfold higher cumulative steroid doses than patients with LBCL. CAR19 expansion was associated with the development of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and the requirement for granulocyte colony-stimulating factor 14 days after infusion. Younger patients and those with elevated lactate dehydrogenase (LDH) had significantly higher CAR19 expansion. In general, no association between CAR19 expansion and LBCL treatment response was observed. However, when controlling for tumor burden, we found that lower CAR19 expansion in conjunction with low LDH was associated with improved outcomes in LBCL. In sum, this study finds CAR19 expansion principally associates with CAR-related toxicity. Additionally, CAR19 expansion as measured by peripheral blood immunophenotyping may be dispensable to favorable outcomes in LBCL.

Ibrutinib improves the efficacy of anti-CD19-CAR T-cell therapy in patients with refractory non-Hodgkin lymphoma.

The efficacy and side effects of the second-time humanized CD19 chimeric antigen receptor (CD19-CAR) T-cell therapy after unsuccessful first-time anti-CD19-CAR T-cell therapy and subsequent ibrutinib salvage treatment were observed in patients with refractory B-cell lymphoma. In our study, 3 patients with refractory mantle cell lymphoma (MCL) and 4 patients with refractory follicular lymphoma (FL) reached stable disease (SD), partial remission (PR), or progression of disease (PD) after first-time humanized anti-CD19-CAR T-cell therapy. They received ibrutinib as a salvage treatment and kept an SD in the following 7-16 mo, but their disease progressed again during ibrutinib salvage treatment. All 7 patients received a second-time humanized anti-CD19-CAR T-cell therapy, which was the same as their first-time anti-CD19-CAR T-cell therapy. In total, 3 MCL patients and 3 FL patients reached complete response (CR) with the second-time anti-CD19-CAR T-cell therapy combined with ibrutinib, whereas 1 FL patient reached PR. There were no differences in the transduction efficiency and proliferation between the 2 instances of anti-CD19-CAR T-cell therapy. However, the second-time anti-CD19-CAR T-cell therapy led to higher peaks of anti-CD19-CAR T cells and anti-CD19-CAR gene copies, but also to higher grades of cytokine release syndrome (CRS) and more serious hematological toxicity. The successful outcome of the second-time anti-CD19-CAR T-cell therapy might suggest that the previous ibrutinib treatment improved the activities of anti-CD19-CAR T cells.

Treatment patterns and outcomes of older patients with mantle cell lymphoma in an Asian population.

BACKGROUND: Significant progress has been made in the treatment outcomes of mantle cell lymphoma (MCL) since the introduction of cytarabine and rituximab in modern regimens. However, older patients may not readily tolerate these agents nor derive benefit. We investigated the impact of age on treatment patterns and clinical outcomes of MCL patients in an Asian population. METHODS: A retrospective study was conducted on patients (n = 66) diagnosed with MCL at the National Cancer Centre Singapore between 1998 and 2018. The median follow-up duration was 40 months. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. RESULTS: The median age of the cohort was 59 years (range, 26-84), with a male predominance (73%). The majority (86%) had advanced stage 3-4 disease at diagnosis. Compared with younger patients, older patients aged ≥60 years (n = 32; 48.5%) presented more frequently with B-symptoms (75% vs 38%, p = 0.0028), anaemia (75% vs 35%, p = 0.0013), and carried higher prognostic risk scores (sMIPI high risk 84% vs 56%, p = 0.016). Non-cytarabine-based induction chemotherapy was more commonly administered in older patients (76% vs 32%, p = 0.0012). The 5-year overall survival (OS) and progression-free survival (PFS) was 68 and 25% respectively. In a multivariable model, older age (HR 3.42, 95%CI 1.48-7.92, p = 0.004) and anemia (HR 2.56, 95%CI 1.10-5.96, p = 0.029) were independently associated with poorer OS while older age (HR 2.24, 95%CI 1.21-4.14, p = 0.010) and hypoalbuminemia (HR 2.20, 95%CI 1.17-4.13, p = 0.014) were independently associated with poorer PFS. In an exploratory analysis, maintenance rituximab following induction chemotherapy improved PFS in younger patients, with median PFS of 131 months and 45 months with or without maintenance therapy respectively (HR 0.39, 95%CI 0.16-0.93, p = 0.035). In contrast, no survival benefit was observed in older patients. CONCLUSIONS: We demonstrated in our analysis that older patients with MCL may harbor adverse clinical features and may not derive benefit from maintenance rituximab, highlighting the need for further research in this area of need.

Safety and antitumor activity of acalabrutinib for relapsed/refractory B-cell malignancies: A Japanese phase I study.

This multicenter, open-label, phase I study assessed the safety and antitumor activity of acalabrutinib in Japanese patients with relapsed/refractory (r/r) B-cell malignancies. Parts 1 (dose confirmation) and 2 (dose expansion) of this three-part study are reported. Treatment was a single dose of 100 mg acalabrutinib (day 1), followed by a washout period and then twice daily 100 mg acalabrutinib in part 1, or twice daily 100 mg acalabrutinib in part 2. Patients from parts 1 and 2 with r/r chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and r/r mantle cell lymphoma (MCL) were assessed as r/r CLL/SLL and r/r MCL cohorts, respectively. Twenty-five patients received treatment (part 1, n = 6). Median age was 71.0 years. Nine (one patient from part 1) and 13 (two patients from part 1) patients were included in the r/r CLL/SLL and r/r MCL cohorts, respectively. Treatment-related adverse events (AEs) occurred in 88% of patients (grade ≥3, 36%); the most common were headache (28%) and purpura (24%), both grade 1/2. No AEs resulted in treatment discontinuation or death. Median duration of treatment was 31, 20, and 7 months for part 1, r/r CLL/SLL cohort, and r/r MCL cohort, respectively. Overall response rate (ORR) was 89% and 62% for the r/r CLL/SLL and r/r MCL cohorts, respectively. The median progression-free survival (PFS) was not reached for the r/r CLL/SLL cohort and was 7 months for the r/r MCL cohort. Acalabrutinib (100 mg twice daily) was generally safe and well-tolerated in adult Japanese patients with B-cell malignancies.

Targeted locus amplification to detect molecular markers in mantle cell and follicular lymphoma.

Minimal residual disease (MRD) monitoring by PCR methods is a strong and standardized predictor of clinical outcome in mantle cell lymphoma (MCL) and follicular lymphoma (FL). However, about 20% of MCL and 40% of FL patients lack a reliable molecular marker, being thus not eligible for MRD studies. Recently, targeted locus amplification (TLA), a next-generation sequencing (NGS) method based on the physical proximity of DNA sequences for target selection, identified novel gene rearrangements in leukemia. The aim of this study was to test TLA in MCL and FL diagnostic samples lacking a classical, PCR-detectable, t(11; 14) MTC (BCL1/IGH), or t(14; 18) major breakpoint region and minor cluster region (BCL2/IGH) rearrangements. Overall, TLA was performed on 20 MCL bone marrow (BM) or peripheral blood (PB) primary samples and on 20 FL BM, identifying a novel BCL1 or BCL2/IGH breakpoint in 16 MCL and 8 FL patients (80% and 40%, respectively). These new breakpoints (named BCL1-TLA and BCL2-TLA) were validated by ASO primers design and compared as MRD markers to classical IGH rearrangements in eight MCL: overall, MRD results by BCL1-TLA were superimposable (R Pearson = 0.76) to the standardized IGH-based approach. Moreover, MRD by BCL2-TLA reached good sensitivity levels also in FL and was predictive of a primary refractory case. In conclusion, this study offers the proof of principle that TLA is a promising and reliable NGS-based technology for the identification of novel molecular markers, suitable for further MRD analysis in previously not traceable MCL and FL patients.

Noninvasive Monitoring of Mantle Cell Lymphoma by Immunoglobulin Gene Next-Generation Sequencing in a Phase 2 Study of Sequential Chemoradioimmunotherapy Followed by Autologous Stem-Cell Rescue.

BACKGROUND: Minimal residual disease (MRD) monitoring has been used to identify early molecular relapse and predict clinical relapse in mantle cell lymphoma (MCL). Few published data exist in MCL on the performance of next-generation sequencing-based assay of immunoglobulin gene rearrangements for MRD assessment. PATIENTS AND METHODS: In a prospective clinical trial (NCT01484093) with intensive induction chemotherapy and autologous stem-cell transplantation, posttreatment peripheral blood samples were collected from 16 MCL patients and analyzed with an earlier version of the Adaptive Biotechnologies MRD assay. RESULTS: Of the 7 patients whose disease remained in remission, the MRD test remained negative in 5 (71%). Of the 9 patients who experienced relapse, the MRD test was positive at least 3 months before relapse in 6 patients (67%) and positive at the time of relapse in 1 patient (11%). All patients with at least 2 positive MRD tests experienced relapse. CONCLUSION: The next-generation sequencing-based MRD assay identified early molecular relapse, and we observed more sensitivity in the cellular (circulating leukocytes) versus acellular (plasma cell-free DNA) compartment. This observation may be due to availability of tumor target or a limitation of the assay.

Lenalidomide maintenance after autologous haematopoietic stem-cell transplantation in mantle cell lymphoma: results of a Fondazione Italiana Linfomi (FIL) multicentre, randomised, phase 3 trial.

BACKGROUND: Fit patients with mantle cell lymphoma aged 18-65 years are usually given cytarabine and rituximab-based induction regimens followed by autologous haematopoetic stem-cell transplantation (HSCT). We investigated whether post-autologous HSCT maintenance with lenalidomide improves progression-free survival in this population. METHODS: This open-label, randomised, multicentre, phase 3 trial was done at 49 haematology and oncology units in Italy and Portugal. Eligible patients had Ann Arbor stage III or IV treatment-naive mantle cell lymphoma (or stage II plus bulky disease [≥5 cm] or B symptoms), and had evidence of cyclin D1 overexpression or the translocation t(11;14)(q13;q32). Patients were aged 18-59 years with Eastern Cooperative Oncology Group (ECOG) performance status 0-3, or aged 60-65 years with ECOG 0-2. After an optional prephase with vincristine and steroids (intravenous vincristine 1·4 mg/m2 on day 1, oral prednisone 100 mg [total dose] on days 1-5), patients were given three courses of R-CHOP (21-day cycle, intravenous rituximab 375 mg/m2 on day 1; intravenous doxorubicin 50 mg/m2, vincristine 1·4 mg/m2, and cyclophosphamide 750 mg/m2 on day 2; oral prednisone 100 mg/m2 on day 2-6). Patients then received one cycle of high-dose CTX (intravenous cyclophosphamide 4 g/m2 on day 1, intravenous rituximab 375 mg/m2 on day 4). After restaging, patients received two cycles of R-HD-cytarabine (high-dose intravenous cytarabine 2 g/m2 every 12 h on days 1-3, intravenous rituximab 375 mg/m2 on days 4 and 10). Patients with complete remission or partial remission proceeded to autologous HSCT and responding patients (complete remission or partial remission) with haematological recovery were randomly assigned (1:1) to receive 24 courses of oral lenalidomide maintenance (15 mg per day for patients with platelets >100 × 109 cells per L or 10 mg per day for platelets 60-100 × 109 cells per L, days 1-21 every 28 days) for 24 months, or observation. The primary endpoint was progression-free survival, measured in the randomised population. This study is registered with EudraCT (2009-012807-25) and ClinicalTrials.gov (NCT02354313). FINDINGS: Between May 4, 2010, and Aug 24, 2015, 303 patients were screened for inclusion and 300 patients were enrolled (median age 57 years, IQR 51-62; 235 [78%] male). 95 patients were excluded before randomisation, mostly due to disease progression, adverse events, and inadequate recovery. 104 patients were randomly assigned to the lenalidomide maintenance group and 101 patients to the observation group. 11 (11%) of 104 patients assigned to lenalidomide did not start treatment (3 withdrew, 6 adverse events or protocol breach, 2 lost to follow-up). At a median follow-up of 38 months after randomisation (IQR 24-50), 3-year progression-free survival was 80% (95% CI 70-87) in the lenalidomide group versus 64% (53-73) in the observation group (log-rank test p=0·012; hazard ratio 0·51, 95% CI 0·30-0·87). 41 (39%) of 104 patients discontinued lenalidomide for reasons including death or progression. Treatment-related deaths were recorded in two (2%) of 93 patients in the lenalidomide group (1 pneumonia, 1 thrombotic thrombocytopenic purpura), and one (1%) of 101 in the observation group (pneumonia). 59 (63%) of 93 patients in the lenalidomide group had grade 3-4 haematological adverse events versus 12 (12%) of 101 patients in the observation group (p<0·0001). 29 (31%) of 93 patients in the lenalidomide group and eight (8%) of 101 patients in the observation group had grade 3-4 non-haematological adverse events (p<0·0001), of which infections were the most common.Serious adverse events were reported in 22 (24%) of 93 patients in the lenalidomide group and five (5%) of 101 patients in the observation group. Pneumonia and other infections were the most common serious adverse events. INTERPRETATION: Despite non-negligibile toxicity, lenalidomide after autologous HSCT improved progression-free survival in patients with mantle cell lymphoma, highlighting the role of maintenance in mantle cell lymphoma. FUNDING: Fondazione Italiana Linfomi and Celgene.

No transmission of SARS-CoV-2 in a patient undergoing allogeneic hematopoietic cell transplantation from a matched-related donor with unknown COVID-19.

The Hematology Department and its Hematopoietic Cell Transplantation (HCT) program implemented several measures during COVID-19 outbreak in order to keep clinical activities with the maximum security for both donors and recipients. Nevertheless, there was a lack of evidence whether blood products and specifically bone marrow can cause transfusion-transmitted infection. Initially, there were many uncertainties and did not exist formal recommendations. Before official statements were available, we performed an allogeneic HCT in a 57-year-old male from a related matched donor in the incubation period of COVID-19 where the patient did not develop the disease. Actual epidemiology data suggest that transmission may occur early in the course of infection, even from asymptomatic patients in the incubation period. In our knowledge this is the first case report of an adult hematopoietic cell donor with COVID-19 in the incubation period where the transplant is successfully completed with no transmission of SARS-CoV-2. The low concentration of viral RNA in plasma of patients with COVID-19 could support the safety of blood products, including peripheral blood hematopoietic cells. In conclusion, blood products including hematopoietic stem cells are safe in the context of COVID-19 pandemic.

Ibrutinib does not have clinically relevant interactions with oral contraceptives or substrates of CYP3A and CYP2B6.

Ibrutinib may inhibit intestinal CYP3A4 and induce CYP2B6 and/or CYP3A. Secondary to potential induction, ibrutinib may reduce the exposure and effectiveness of oral contraceptives (OCs). This phase I study evaluated the effect of ibrutinib on the pharmacokinetics of the CYP2B6 substrate bupropion, CYP3A substrate midazolam, and OCs ethinylestradiol (EE) and levonorgestrel (LN). Female patients (N = 22) with B-cell malignancies received single doses of EE/LN (30/150 µg) and bupropion/midazolam (75/2 mg) during a pretreatment phase on days 1 and 3, respectively (before starting ibrutinib on day 8), and again after ibrutinib 560 mg/day for ≥ 2 weeks. Intestinal CYP3A inhibition was assessed on day 8 (single-dose ibrutinib plus single-dose midazolam). Systemic induction was assessed at steady-state on days 22 (EE/LN plus ibrutinib) and 24 (bupropion/midazolam plus ibrutinib). The geometric mean ratios (GMRs; test/reference) for maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC) were derived using linear mixed-effects models (90% confidence interval within 80%-125% indicated no interaction). On day 8, the GMR for midazolam exposure with ibrutinib coadministration was ≤ 20% lower than the reference, indicating lack of intestinal CYP3A4 inhibition. At ibrutinib steady-state, the Cmax and AUC of EE were 33% higher than the reference, which was not considered clinically relevant. No substantial changes were noted for LN, midazolam, or bupropion. No unexpected safety findings were observed. A single dose of ibrutinib did not inhibit intestinal CYP3A4, and repeated administration did not induce CYP3A4/2B6, as assessed using EE, LN, midazolam, and bupropion.

Minimal Residual Disease in Mantle Cell Lymphoma: Methods and Clinical Significance.

Several biological and clinical features have been recognized in mantle cell lymphoma (MCL). In recent years, the minimal residual disease (MRD) has been extensively investigated and is now considered as one of the strongest clinical predictors in this lymphoma. This article reviews methods used for the assessment of MRD in MCL and discusses their strengths and weaknesses. In addition, it examines the MRD contribution to the biology knowledge of MCL and the development of effective strategies for its management, including the possibility of personalized treatment based on MRD response.

Flow cytometry in the diagnosis of mature B-cell lymphoproliferative disorders.

B-lineage lymphoproliferative disorders (LPD) are rather frequent diseases, associated with specific clinical or biological features but also sometimes of fortuitous discovery. Multiparameter flow cytometry plays a major role for a rapid diagnostic indication, on peripheral blood or bone marrow samples in most instances, guiding complementary analyses and allowing for the proper therapeutic management of patients. After describing the important pre-analytical precautions required for an adequate assessment, the immunophenotypic features of small-cell and large-cell lymphomas are described in this review. The ubiquitous expression of CD19 is a first mandatory gating step. A possible clonal proliferation is then suspected by the demonstration of surface immunoglobulin light chain restriction. The aberrant presence of CD5 allows to segregate chronic lymphocytic leukemia and mantle cell lymphoma in most cases. Other LPD exhibit specific immunophenotypic features. A table of useful markers and a decision tree are provided. Of note, immunophenotypic data should as much as possible be interpreted in an integrated manner, involving the patient's clinical and other biological features, and be completed by further chromosomal and/or molecular investigations.

Reverse pseudohyperkalemia and pseudohyponatremia in a patient with B-cell non-Hodgkin lymphoma.

OBJECTIVES: Investigate concomitant and spurious high potassium and low sodium results in heparinized plasma. METHODS: Potassium and sodium values were measured from heparinized plasma and serum in a patient with B-cell non-Hodgkin lymphoma using both an automated chemistry analyzer (indirect ion selective electrode) and blood gas analyzer (direct ion selective electrode). RESULTS: Potassium levels were significantly increased while sodium levels were significantly decreased in heparinized plasma compared to serum on several occasions. CONCLUSIONS: To our knowledge, concomitant reverse pseudohyperkalemia and pseudohyponatremia has not been reported previously. We postulate the discrepancy between plasma and serum sodium (pseudohyponatremia in plasma) may be unique to cases of reverse pseudohyperkalemia with extreme potassium elevations.

25-Hydroxy vitamin D deficiency predicts inferior prognosis in mantle cell lymphoma.

INTRODUCTION: Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkin lymphoma (NHL), and the purpose of this study was to evaluate the prognostic value of 25-hydroxy vitamin D [25-(OH)D] deficiency among patients with MCL. MATERIALS AND METHODS: Seventy MCL patients with serum 25-(OH)D were enrolled in this study. 25-(OH)D deficiency was defined as a 25-(OH)D level lower than 50 nmol/L, according to International standard of 25-(OH)D classification. The univariate and multivariate Cox regression analyses were used to define the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curves and the areas under the curve (AUC) were calculated to evaluate the accuracy of combined MIPI-c with 25-(OH)D deficiency. RESULTS: The results showed that 40 patients had 25-OH vitamin D deficiency, with a median follow-up of 25.5 months (range 3.4-65.7 months). Univariate Cox regression analysis showed that 25-(OH)D deficiency group demonstrated unfavorable PFS (P = 0.003) and OS (P = 0.006). Multivariate Cox regression analysis revealed that 25-(OH)D deficiency was an independent prognosis factor for PFS [hazard ratio (HR) 3.713; 95% confidence interval (CI) 1.822-7.565; P < 0.001], and OS (HR 8.305; 95% CI 2.060-33.481; P = 0.003). 25-(OH)D deficiency combined with MIPI-c showed an improved prognostic capacity. CONCLUSION: In summary, 25-(OH)D deficiency was a promising prognostic predictor for MCL.

Can the prognosis of mantle cell lymphoma be predicted by simple CBC counts?

Mantle cell lymphoma (MCL) exhibits a heterogenous clinical course. The MCL International Prognostic Index (MIPI) is the most commonly used risk classification system in MCL. However, it does not contain a parameter associated with the tumor microenvironment. The aim of this study was to develop a more powerful prognostic index by evaluating the absolute monocyte count (AMC), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) at diagnosis in conjunction with the clinical and laboratory parameters.The data of 96 MCL patients with newly diagnosed from January 2014 to December 2018 were retrospectively evaluated in this study. The AMC, NLR, and PLR cut-off values were determined using the receiver operating characteristic (ROC) analysis.The clinical behavior and results of the disease exhibited significant variation in high and low value groups at the time of diagnosis. In univariate analysis, the AMC ≥ 580, NLR ≥ 2.43, and PLR ≥ 120.85 were determined as negative prognostic factors for 5-year progression free survival (PFS) (AMC: PFS, P < .001; NLR: PFS, P < .001; PLR: PFS, P < .001) and for 5-year overall survival (OS) (P < .001, P < .001, P < .001, respectively). Beta-2 microglobulin (B2-MG), and MIPI for PFS, and for OS were found to be independent risk factors in the multivariate analysis (for PFS: P = .006, P = .002, respectively; and for OS: P = .007, P = .001, respectively). The 5-year OS was 20% in the group with B2-MG ≥ 3.5. The patients in high-risk MIPI group had poorer 5-year OS (median OS: 40 months, P < .001).The results stated that the use of B2-MG in conjunction with MIPI was a more sensitive method in determining the prognosis in MCL (median OS: 12 months in high-risk MIPI group with a B2-MG ≥3.5, P < .001). Additionally, it was found that parameters reflecting the tumor microenvironment such as AMC, NLR, and PLR increased the risk of progression in MCL. In view of these findings, in addition B2-MG to the MIPI to create a more sensitive prognostic scoring system may provide an insight into personalization of treatment with early recognition of patients with poor prognosis.

Association of red blood cell distribution width and outcomes in patients with mantle cell lymphoma.

Red blood cell distribution width (RDW), which measures the range of variation of red blood cell volume, has been explored as a prognostic factor in multiple types of cancer. However, the role of RDW in mantle cell lymphoma (MCL), a rare type of non-Hodgkin lymphoma with poor outcomes, remains to be determined. Therefore, we investigated the prognostic role of RDW in MCL. We found that 21 of 76 MCL patients (27.6%) had an abnormally elevated RDW (>15.7%). Abnormally elevated RDW was significantly associated with presence of B symptoms (P = 0.0020), elevated lactate dehydrogenase (LDH) (P = 0.0010), higher leukocyte count (P = 0.0345), higher simplified Mantle Cell International Prognostic Index (sMIPI) (P = 0.0194), and lower level of hemoglobin (Hb) (P < 0.0001). It was marginally associated with increased C-reactive protein (P = 0.0862). RDW was significantly correlated with Hb level (r2  = 0.42) and LDH level (r2  = 0.19). 15.8% was determined as the best cutoff of RDW in predicting the survival outcome by the X-tile software. Survival analysis revealed that high RDW (>15.8%) predicted shorter progression-free survival (PFS) (hazards ratio [HR]: 3.14; P = 0.0005) and shorter overall survival (OS) (HR: 4.04; P < 0.0001). High RDW independently predicted both shorter PFS (P = 0.0493) and OS (P = 0.0118). RDW also improved the prognostic stratification based on sMIPI. In conclusion, our study identified RDW as a novel prognostic factor of clinical feasibility in the prognostication of MCL.

Low absolute NK cell counts in peripheral blood are associated with inferior survival in patients with mantle cell lymphoma.

BACKGROUND: Although risk stratification of mantle cell lymphoma (MCL) is most frequently performed using the simplified MCL International Prognostic Index (sMIPI), the identification of host-related factors and tumor microenvironment, including absolute monocyte counts (AMC) and peripheral blood T lymphocyte subsets, especially absolute natural killer cell counts (ANKC) has been suggested to be critical in the prediction of prognosis and the guidance of treatment. OBJECTIVE: This study was aimed at investigating whether peripheral blood ANKC and AMC at diagnosis had an impact on MCL prognosis. METHODS: A total of 92 newly diagnosed MCL patients was enrolled in this retrospective study. Flow cytometric analysis was conducted on fresh peripheral blood samples with a FACSCalibur flow cytometer (BD Biosciences, San Jose, CA, USA). RESULTS: The median follow-up was 42 months (range, 2-144 months) and the median overall survival (OS) of all cases was 45 months. High AMC (> 0.6 × 109/L) was the parameter associated with inferior progression free survival (PFS) (P= 0.044) and poor OS (P= 0.028) while low ANKC (⩽ 0.1 × 109/L) was associated with unfavorable OS (P= 0.023) by univariable analysis. Multivariable analysis revealed that only low ANKC (⩽ 0.1 × 109/L) was statistically significant in worse OS (P= 0.009) independent of sMIPI. CONCLUSIONS: Low ANKC (⩽ 0.1 × 109/L) proved to be a significant predictor of inferior OS in patients with MCL.