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.     

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.     

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.     

Detection of extranodal and spleen involvement by FDG-PET imaging predicts adverse survival in untreated follicular lymphoma

Predicting early clinical failure in patients with untreated follicular lymphoma (FL) is important but difficult. This study aimed to determine the incidence and patterns of extranodal (EN) and spleen disease using PET/CT, and assess their utility in predicting early clinical failure. PET/CT images from 613 cases of untreated FL (2003-2016) were reviewed. The location and number of EN sites, patterns of bone involvement, and splenic involvement were recorded. Outcomes were assessed using event-free survival (EFS), overall survival (OS), and early clinical failure at 24 months (EFS24). So, 49% (301/613) of patients had PET/CT-detected EN involvement, and 28% (171/613) had spleen involvement. The presence of ≥2 EN sites, spleen, bone or soft tissue involvement all predicted failure to achieve EFS24. Presence of ≥2 EN sites and bone involvement pattern were also predictive of OS in a univariate analysis. In a multivariate analysis with FLIPI-2 factors, spleen involvement, pattern of bone involvement, and soft tissue involvement independently predicted a lower EFS (HR 1.49 (1.11-2.00), P = .007; HR 1.71 (1.10-2.65), P = .017; and HR 1.67 (1.06-2.62), P = .026, respectively). When the multivariate analysis was performed using PRIMA-PI factors (marrow and B2M), the number of EN sites was an independent prognostic factor for inferior OS (HR 2.28; P = .05). Baseline PET/CT identifies EN involvement in nearly half of patients with untreated FL. The presence of ≥2 EN sites, bone, soft tissue, or splenic involvement predicts early clinical failure. These results, when combined with other factors, may better identify high-risk patients and guide therapy.     

Low absolute lymphocyte count is a poor prognostic marker in patients with diffuse large B-cell lymphoma and suggests patients' survival benefit from rituximab

Objectives: To evaluate the prognostic value of absolute lymphocyte count (ALC) at diagnosis in patients with diffuse large B‐cell lymphoma (DLBCL). Methods: In a large cohort of patients with DLBCL treated with CHOP (n = 119) or RCHOP (n = 102) in our institution, we evaluated the prognostic value of ALC at diagnosis with regards to treatment response, overall (OS) and progression‐free survival (PFS). Use of rituximab, all International Prognostic Index (IPI) determinants, β2microglobulin level, presence of B symptoms or bulky disease, and ALC were evaluated. Results: Low ALC (<1.0 × 10⁹/L) was associated with advanced stage, performance status ≥2, elevated lactate dehydrogenase, number of extranodal involvement ≥2, B symptoms, elevated β2microglobulin and higher IPI risk group. Low ALC was associated with lower CR rate by univariate analysis (odds ratio = 3.29, P = 0.024) but not by multivariate analysis. By univariate analysis using Cox proportional hazard model, low ALC was associated with shorter OS [hazard ratio (HR) = 2.89, P < 0.001] and PFS (HR = 2.91, P < 0.001). Multivariate analysis revealed that low ALC was associated with shorter OS (HR = 2.51, P = 0.003) and PFS (HR = 2.72, P < 0.001), independent of above‐mentioned parameters. Subclass analyses revealed that the use of rituximab improves OS in patients with low ALC (HR = 0.42, P = 0.05) but not in those with high ALC (HR = 0.83, P = 0.71). This observation was most obvious in patients with higher IPI score. Conclusion: Low ALC is a poor prognostic marker in patients with DLBCL and suggests patients’ survival benefit from rituximab.     

Clinical outcomes of multiple myeloma patients who undergo autologous hematopoietic stem cell transplant with G-CSF or G-CSF and plerixafor mobilized grafts

Impact of Plerixafor (P) mobilized stem cells on immune reconstitution, such as absolute lymphocyte count at day 30 (ALC30), and on long-term outcomes of Multiple Myeloma (MM) patients undergoing autologous stem cell transplant (ASCT) has not been well established. We evaluated total of 469 patients mobilized with G-CSF (G) alone, and 141 patients mobilized with G-CSF plus plerixafor (G+ P). Patients only received plerixafor if they had peripheral blood CD34⁺ blood count <20/μL on first planned day of collection. Primary endpoint, ALC30, was 1.3 K/μL (range, 0.1-4.5) and 1.2 K/μL (range, 0.1-5.1) for G and G + P, respectively (P =. 61). The median PFS was 2.5 years (95% CI, 2.1-3.2) and 2.8 years (95% CI, 2.0-3.3) for G and G + P, respectively (HR: 1.13; 95% CI, 0.84-1.50; P = .42). The median OS was 6.1 years (95% CI, 4.6-NR) for G group compared to 3.7 years (95% CI, 3.2-NR) for the G + P group (HR: 1.64; 95% CI, 1.12-2.40; P = .01). The median follow-up time for OS was 2.53 years (95% CI, 2.13-2.99) and 1.59 years (95% CI, 1.17-2.02) for G and G+ P group, respectively. In this large retrospective analysis of MM patients mobilized with G-CSF vs G-CSF + P, there was no significant difference in lymphocyte recovery or PFS. There was an overall survival difference in patients who were poor mobilizers and could not be mobilized with G-CSF alone.     

Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma

Autologous stem cell transplantation (ASCT) improves survival in patients with previously untreated multiple myeloma (MM) and relapsed, chemotherapy-sensitive, aggressive non-Hodgkin lymphoma (NHL). Lower relapse rates seen in allogeneic stem cell transplantation have been related to early absolute lymphocyte count (ALC) recovery as a manifestation of early graft-verus-tumor effect. In ASCT, the relation between ALC recovery and clinical outcomes in MM and NHL was not previously described. This is a retrospective study of patients with MM and NHL who underwent ASCT at the Mayo Clinic between 1987 and 1999. The ALC threshold was determined at 500 cells/microL on day 15 after ASCT. The study identified 126 patients with MM and 104 patients with NHL. The median overall survival (OS) and progression-free survival (PFS) times for patients with MM were significantly longer in patients with an ALC of 500 cells/microL or more than patients with an ALC of fewer than 500 cells/microL (33 vs 12 months, P <.0001; 16 vs 8 months, P <.0003, respectively). For patients with NHL, the median OS and PFS times were significantly longer in patients with an ALC of 500 cells/microL or more versus those with fewer than 500 cells/microL (not reached vs 6 months, P <.0001; not reached vs 4 months, P <.0001, respectively). Multivariate analysis demonstrated day 15 ALC to be an independent prognostic indicator for OS and PFS rates for both groups of patients. In conclusion, ALC is correlated with clinical outcome and requires further study. (Blood. 2001;98:579-585)     

Outcomes of treatment for relapsed acute lymphoblastic leukaemia in children with Down syndrome

Children with Down syndrome (DS) have a greater risk for developing both acute lymphoblastic leukaemia (ALL) and significant adverse effects of chemotherapy. We investigated their outcome with, and tolerance of, treatment protocols for relapsed ALL optimized in the paediatric population without DS. Probability of survival and causes of treatment failure were determined for 49 children with DS and a matched cohort of 98 children without DS among 2160 children treated for relapsed ALL in clinical trials conducted by the Berlin‐Frankfurt‐Münster ALL Relapse Study Group between 1983 and 2012. Despite more favourable ALL relapse characteristics, children with DS experienced lower event‐free (EFS) and overall survival (OS) than the control group without DS (EFS 17 ± 08% vs. non‐DS 41 ± 06%, P = 0·006; OS 17 ± 09% vs. non‐DS 51 ± 06%, P < 0·001). Children with DS developed more frequently fatal complications of treatment (34 ± 07% vs. non‐DS 10 ± 04%, P < 0·001). During the last decade, EFS and OS were no longer significantly different in children with and without DS (EFS 31 ± 09% vs. 36 ± 09%, P = 0·399; OS 31 ± 12% vs. 53 ± 09%, P = 0·151). DS proved an independent prognostic factor of outcome after ALL relapse. Induction deaths and treatment‐related mortality but not subsequent relapse were the main barrier to successful outcomes of relapse therapy in children with DS.     

The clinical impact of time to response in de novo accelerated-phase chronic myeloid leukemia

We aimed to describe the impact of time to response on the outcomes of 75 patients with accelerated-phase chronic myeloid leukemia (CML-AP) at diagnosis. Patients had at least 1 feature of AP: blasts ≥15% (n = 2), basophils ≥20% (n = 19), platelets <100 × 10⁹/L (n = 7), cytogenetic clonal evolution (n = 34), or more than one factor (n = 13). Thirty-three patients received imatinib; 42 received a second-generation tyrosine kinase inhibitor (2GTKI) (19 dasatinib and 23 nilotinib). We used chi-square and Kaplan-Meier analyses to determine the impact of various degrees of molecular and cytogenetic response at early time points (3 and 6 months) on rates of overall cytogenetic and molecular response, overall survival (OS), event-free survival (EFS), transformation-free survival (TFS), and failure-free survival (FFS). After a median follow-up of 96 months (range: 18-224 months), the overall rate of complete cytogenetic response was 79%, of major molecular response, 71%, and of molecular reponse (MR)4.5, 59%. Patients who achieved a major cytogenetic response (MCyR) (n = 49) at 3 months had significantly better 3-year OS (94% vs 75%; P = .002), TFS (98% vs 73%; P < .001), EFS (93% vs 42%; P < .001), and FFS (83% vs 25%; P < .001) rates than patients who did not have MCyR at 3 months. Most (67%) who eventually achieved sustained MR4.5 had achieved MCyR at 3 months. In de novo CML-AP, early response at 3 and 6 months is a strong determinant of long-term outcome.     

Bortezomib reinduction chemotherapy in high-risk ALL in first relapse: a report from the Children's Oncology Group

While survival in paediatric acute lymphoblastic leukaemia (ALL) is excellent, survival following relapse is poor. Previous studies suggest proteasome inhibition with chemotherapy improves relapse ALL response rates. This phase 2 Children's Oncology Group study tested the hypothesis that adding the proteasome inhibitor bortezomib to chemotherapy increases complete response rates (CR2). Evaluable patients (n = 135, 103 B-ALL, 22 T-ALL, 10 T-lymphoblastic lymphoma) were treated with reinduction chemotherapy plus bortezomib. Overall CR2 rates were 68 ± 5% for precursor B-ALL patients (<21 years of age), 63 ± 7% for very early relapse (<18 months from diagnosis) and 72 ± 6% for early relapse (18–36 months from diagnosis). Relapsed T-ALL patients had an encouraging CR2 rate of 68 ± 10%. End of induction minimal residual disease (MRD) significantly predicted survival. MRD negative (MRDneg; MRD <0·01%) rates increased from 29% (post-cycle 1) to 64% following cycle 3. Very early relapse, end-of-induction MRDneg precursor B-ALL patients had 70 ± 14% 3-year event-free (EFS) and overall survival (OS) rates, vs. 3-year EFS/OS of 0–3% (P = 0·0001) for MRDpos (MRD ≥0·01) patients. Early relapse patients had similar outcomes (MRDneg 3-year EFS/OS 58–65% vs. MRDpos 10–19%, EFS P = 0·0014). These data suggest that adding bortezomib to chemotherapy in certain ALL subgroups, such as T-cell ALL, is worthy of further investigation. This study is registered at http://www.clinical.trials.gov as NCT00873093.     

Peripheral blood blast clearance is an independent prognostic factor for survival and response to acute myeloid leukemia induction chemotherapy

In patients with acute myeloid leukemia (AML), rapid reduction of circulating blasts with induction chemotherapy may serve as an in vivo marker of chemosensitivity. We performed a retrospective analysis of 363 patients with untreated AML who received induction chemotherapy in order to determine the relationship between day of blast disappearance (DOBD) and complete remission (CR) rates, event‐free survival (EFS), and overall survival (OS). DOBD ≤ 5 vs. >5 was identified as the most discriminating cutoff for OS. DOBD > 5 was observed in 35 patients (9.6%). The CR rate for patients with DOBD ≤ 5 vs. >5 was 74.0 and 28.6%, median EFS was 9.4 and 1.8 months, and median OS was 17.1 and 5.8 months, respectively (P < 0.001 for all). DOBD > 5 was independently associated with a lower CR rate and shorter EFS and OS (P < 0.001 for all). DOBD > 5 retained prognostic significance for EFS and OS when patients were stratified by cytogenetic risk group, de novo vs. secondary or therapy‐related AML, European LeukemiaNet‐based risk groups, and whether CR was achieved. We propose DOBD > 5 as a simple and early marker of disease resistance that identifies patients with poor prognosis who otherwise may not be identified with existing risk stratification systems. Am. J. Hematol. 91:1221–1226, 2016. © 2016 Wiley Periodicals, Inc.     

Prognostic significance of serum cystatin C in multiple myeloma

Multiple myeloma (MM) is frequently complicated by renal insufficiency, which is associated with an unfavorable prognosis. Serum cystatin C is a new and accurate marker of glomerular filtration rate. Global gene expression analysis has revealed serum cystatin C as one of the most highly upregulated genes in MM. Recent data have shown serum cystatin C as an independent prognostic marker in MM. To further elucidate the prognostic significance of serum cystatin C, we investigated pretreatment serum cystatin C levels in 68 newly diagnosed patients homogeneously treated with high-dose melphalan followed by autologous stem cell transplantation. Median serum cystatin C level in MM patients was significantly higher than in the 66 healthy controls (1.07 vs. 0.74 mg/L [p = 0.002]). Median serum cystatin C levels significantly increased with higher International Staging System (ISS) stages (stage I 0.72 mg/L; stage II 0.89 mg/L; stage III 1.28 mg/L; p < 0.0001). Higher serum cystatin C was positively correlated with higher serum levels of creatinine (r = 0.84; p < 0.0001), β2-microglobulin (r = 0.72; p < 0.0001), LDH (r = 0.43; p = 0.0003), white blood cell counts (r = 0.61; p < 0.0001) and calcium (r = 0.29; p = 0.016), and negatively correlated with lower serum albumin levels (r = 0.44; p < 0.0001) and hemoglobin levels (r = 0.31; p = 0.01). Using ROC analysis, patients with serum cystatin C levels ≥0.95 mg/L (n = 24) had a significantly shorter event-free survival (EFS) and overall survival (OS) than patients with serum cystatin C levels <0.95 mg/L (median EFS: 26 vs. 44 months, p < 0.0001; median OS: 54 vs. 68 months, p = 0.05). Moreover, the combination of serum cystatin C level and genomic aberrations further refined the prognostic information (EFS and OS) provided by either one of the factors. The level of serum cystatin C is not only a sensitive marker of renal function, but also reflects tumor burden and delivers prognostic information in MM.     

Bone marrow necrosis in acute leukemia: Clinical characteristic and outcome

Bone marrow necrosis (BMN) is characterized by infarction of the medullary stroma, leading to marrow necrosis with preserved cortical bone. In reported small series, BMN in hematological malignancies is associated with poor prognosis. We sought to find the impact of BMN on clinical outcome in a relatively larger cohort of patients with acute leukemias. Overall we evaluated 1,691 patients; 1,051 with acute myeloid leukemia (AML) and 640 with acute lymphocytic leukemia referred to our institution between 2002 and 2013. Patients with AML and acute lymphoblastic leukemia (ALL) were evaluated separately to determine the incidence of BMN, associated clinical features and its prognostic significance. At initial diagnosis, BMN was observed in 25 (2.4%) patients with AML and 20 (3.2%) patients with ALL. In AML, BMN was significantly associated with French–American–British AML M5 morphology (32% vs. 10%, P = 0.002). The complete remission (CR) rate in AML with and without BMN was 32% and 59% respectively (P = 0.008). Likewise, CR rate in ALL with BMN was also inferior, 70% vs. 92% (P = 0.005). The median overall survival (OS) in AML with BMN was significantly poorer, 3.7 months compared to 14 months without BMN (P = 0.003). Similarly, the median OS in ALL with and without BMN was 61.7 and 72 months respectively (P = 0.33). BMN is not a rare entity in AML and ALL, but is infrequent. BMN in AML and in ALL is suggestive of inferior response and poor prognosis. Am. J. Hematol. 90:769–773, 2015. © 2015 Wiley Periodicals, Inc.     

The long-term results of childhood acute lymphoblastic leukemia at two centers from Turkey: 15 years of experience with the ALL-BFM 95 protocol

Dramatic progress in the treatment of childhood acute lymphoblastic leukemia (ALL) has been achieved during the last two decades in Western countries, where the 5-year event-free survival (EFS) rate has risen from 30 to 85 %. However, similarly high cure rates have not always been achieved in all centers in developing countries due to limited sources. We evaluated the treatment results of the ALL-Berlin–Frankfurt–Münster (BFM) 95 protocol as used between 1995 and 2009 in the pediatric hematology departments of two university hospitals. A retrospective analysis of 343 children newly diagnosed with ALL (M/F 200/143, median age 6.8 years) was performed. The overall survival (OS) and EFS according to age, initial leukocyte count, immunophenotype, chemotherapy responses (on days 8, 15, and 33), and risk groups were analyzed by Kaplan–Meier survival analysis. Median follow-up time was 6.4 years. Complete remission was achieved in 97 % of children. Five-year EFS and OS were found to be 78.4 and 79.9 %, respectively. Children younger than 6 years old had significantly better EFS and OS (83.7 and 85.2 %) than children aged ≥6 years (71.4 and 72.8 %). Adolescents achieved 63 % EFS and 65 % OS. Patients who had initial leukocyte counts of <20?×?10⁹/L had better EFS and OS (82.2 and 84.6 %) than children with higher initial leukocyte counts (72.6 and 72.6 %). EFS for B-cell precursor and T-cell ALL was 81.5 and 66.7 %, respectively. Children with a good response to prednisolone on day 8 (87 %) achieved significantly better EFS and OS (81.2 and 81.9 % vs. 55.3 and 60.5 %). Children whose bone marrow on day 15 was in complete remission had higher EFS and OS (83.7 and 86.6.1 % vs. 56.4 and 61.5 %). Children in the standard-risk and medium-risk groups obtained statistically significantly higher EFS (95.5 and 82.7 %) and OS (97.7 and 82.3 %) compared to the high-risk group (EFS 56.3 %, OS 63.4 %). The relapse rate was 14.8 %. The median relapse time from diagnosis was 23.2 months. Death occurred in 69 of 343 patients (20.1 %). The major causes of death were infection and relapse. None of the patients died of drug-related toxicity. The ALL-BFM 95 protocol was applied successfully in these two centers. In developing countries in which minimal residual disease cannot be monitored, this protocol can still be used with high survival rates.     

Monocytosis in polycythemia vera: Clinical and molecular correlates

Monocytosis (absolute monocyte count, AMC ≥ 1 × 10⁹/L) might accompany a spectrum of myeloid neoplasms, other than chronic myelomonocytic leukemia (CMML). In the current study, we examined the prevalence, laboratory and molecular correlates, and prognostic relevance of monocytosis in polycythemia vera (PV). Among 267 consecutive patients with World Health Organization (WHO)‐defined PV, 55 (21%) patients displayed an AMC of ≥1 × 10⁹/L and 18 (7%) an AMC of ≥1.5 × 10⁹/L. In general, PV patients with monocytosis were significantly older and displayed higher frequencies of leukocytosis (81% vs. 50% at AMC ≥1 × 10⁹/L) and TET2/SRSF2 mutations (57%/29% vs. 19%/1% at AMC ≥ 1.5 × 10⁹/L). In univariate analysis, AMC ≥1.5 × 10⁹/L adversely affected overall (OS; P = .004; HR 2.6, 95% CI 1.4‐4.8) and myelofibrosis‐free (MFFS; P = .02; HR 4.4, 95% CI 1.3‐15.1) survival; during multivariable analysis, significance was borderline sustained for OS (P = .05) and MFFS (P = .06). Other independent risk factors for OS included unfavorable karyotype (P = .02, HR 3.39, 95% CI 1.17‐9.79), older age (P < .0001, HR 3.34 95% CI 1.97‐5.65), and leukocytosis ≥15 × 10⁹/L (P = .004, HR 2.04, 95% CI 1.26‐3.29). In conclusion, in the current study, we encountered a higher than expected prevalence of monocytosis in patients with PV and the mutation profile and age distribution of PV patients with monocytosis is akin to those of patients with CMML and might partly contribute to their worse prognosis.     

Short progression-free survival predicts for poor overall survival in older patients with multiple myeloma treated upfront with novel agent-based therapy

Objectives: To assess the importance of the quality of response and of early relapse in unselected elderly patients with myeloma treated upfront with novel agents. Methods: We analyzed 135 unselected transplant‐ineligible patients older than 65 yr who were treated upfront with novel agent‐based regimens in a single center. Results: On intent to treat, 81% of patients achieved a response (28% sCR/CR, 23% VGPR, and 30% PR). Median progression‐free survival (PFS) for patients who achieved sCR/CR was 31 vs. 20 months for VGPR and 23 months for PR (P = 0.048). Median overall survival (OS) for patients with sCR/CR was 62 months, 53 months for VGPR and 38 months for patients with PR (P = 0.028). Early relapse (PFS < 12 months) was more common in patients with PR (39% vs. 21% for VGPR vs. 3% for sCR/CR). Patients who relapsed or progressed <12 months from initiation of treatment had a median OS of 15.4 months compared with 53 months (P < 0.001) for patients who had a PFS > 12 months despite the fact that after relapse or progression most patients were treated again with novel agents. In multivariate analysis, short PFS was the most significant adverse prognostic factor affecting OS, associated with a 7.25‐fold (P < 0.0001) increase in the risk of death. Conclusion: In newly diagnosed patients over 65 yr, treated upfront with novel agents achievement of CR and a PFS ≥12 months is associated with improved outcome. Patients who fail to respond or experience early relapse after primary therapy with novel agent‐based regimens should be encouraged to participate in clinical trials of novel agents and combinations.     

A genome‐wide single‐nucleotide polymorphism‐array can improve the prognostic stratification of the core binding factor acute myeloid leukemia

Core binding factor (CBF) AML with the D816 C‐KIT gene mutation demonstrate inferior treatment outcomes. However, the remaining cases without the D816 C‐KIT mutation imply a requirement of more sophisticated dissection of the patients according to their prognosis. In this study, we analyzed the prognostic value of a single nucleotide polymorphism array (SNP‐A) based karyotyping combined with metaphase cytogenetics (MC) to facilitate further stratification of CBF AML patients. A total of 98 CBF AML patients were included and genome‐wide Human SNP 6.0 Arrays (Affymetrix) were performed using marrow samples taken at diagnosis. Overall, 40 abnormal lesions were identified in 25 patients (26%). Survival of the patients with the abnormal lesion(s) detected by SNP‐A and/or MC was worse than those without lesions in terms of the 2‐year overall survival (OS; 57.5% vs. 76.4%, P = 0.028), event‐free (EFS; 45.7% vs. 66.2%, P = 0.072), and leukemia‐free survival (LFS; 49.0% vs. 77.4%, P = 0.015), specially in the subgroup with inv(16)/t(16;16) (40.9% vs. 80.2% OS, P = 0.040) and in the subgroup without the D816 C‐KIT mutation (61.6% vs. 82.7% OS, P = 0.038). Multivariate analysis confirmed the prognostic impact of the abnormal SNP‐A and/or MC lesion on EFS (HR 2.011, P = 0.047), and LFS (HR 3.231, P = 0.005) in the overall CBF AML. This study suggests that the combined use of SNP‐A with MC in the CBF AML can provide important prognostic value, especially in the inv(16)/t(16;16) subgroup or in the patients without the D816 C‐KIT mutation. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.     

Prognostic implications of CD14 positivity in acute myeloid leukemia arising from myelodysplastic syndrome

Secondary acute myeloid leukemia (s-AML) arising from myelodysplastic syndrome (MDS) shows different clinical features from de novo AML. We assessed the prognostic significance of immunophenotypic markers in patients with s-AML arising from MDS. Sixty-five adults diagnosed with AML arising from MDS between 1996 and 2010 were retrospectively analyzed. Immunophenotyping was performed for markers including CD3, CD7, CD10, CD13, CD14, CD19, CD33, CD34, CD41, CD45, CD56, CD65, CD117, HLA-DR, and TdT. Of these immunophenotypic markers, only CD14 positivity was significantly associated with lower complete remission rate (P = 0.034) and significantly shorter overall survival (OS, P < 0.001) and event-free survival (EFS, P < 0.001) on univariate analysis. On multivariate analysis, these differences remained significant in terms of OS [hazard ratio (HR) 4.49; P < 0.001] and EFS (HR 4.06; P < 0.001). Other significant prognostic variables included age ≥60 years [shorter OS (P = 0.003) and EFS (P = 0.020)], higher WBC count (>60,000/μL) [shorter OS (P < 0.001) and EFS (P = 0.001)], and poor cytogenetic risk group [shorter OS (P = 0.005)]. CD14 expression on leukemic blasts is an independent prognostic factor for survival outcomes in patients with AML arising from MDS.     

Combined use of peripheral blood blast count and platelet count during and after induction therapy to predict prognosis in children with acute lymphoblastic leukemia

Several studies have reported an association between the rapidity of reduction in peripheral blood blast count or recovery of normal hematopoiesis and treatment outcome during therapy in children with acute lymphoblastic leukemia (ALL). However, little is known about the impact of both of these aspects on prognosis in pediatric ALL. Accordingly, the purpose of this study was to evaluate whether the combined use of blood blast count and platelet count could predict event-free survival (EFS) and overall survival (OS) when minimal residual disease (MRD) detection was not available.A total of 419 patients aged 0 to 14 years diagnosed and treated for ALL between 2011 and 2015 were enrolled.Patients with a blast count ≥0.1 × 10⁹/L on day 8 exhibited significantly lower survival rates than that in those with blast counts <0.1 × 10⁹/L. The EFS and OS in patients with platelet count ≥100 × 10⁹/L on day 33 were significantly higher than those with platelet counts <100 × 10⁹/L. In univariate and multivariate analyses, patients with low blast count on day 8 and high platelet count on day 33 were significantly associated with better EFS and OS. The combination of blast cell count on day 8 and platelet count on day 33 demonstrated a strong association with MRD-based risk stratification.Complete blood count is an inexpensive, easy to perform, and reliable measurement in children with ALL. The combination of blast count and platelet count during and after induction chemotherapy was a significant and independent prognostic factor for treatment outcome in pediatric ALL.     

Early lymphocyte recovery predicts longer survival after autologous peripheral blood stem cell transplantation in multiple myeloma

To understand the prognostic value of lymphocyte recovery after autologous peripheral blood stem cell transplantation (APBSCT), we performed a retrospective study of 59 newly diagnosed multiple myeloma (MM) patients who underwent frontline APBSCT. Conditioning regimens were melphalan 100 mg/m(2) for 2 days. Following APBSCT, all patients showed complete or partial response. Median follow-up time was 29.57 months and median recovery of absolute lymphocyte count (ALC) > or =1000/mm(3) was 23 days. Univariate analysis revealed that significant predictors of overall survival (OS) included bone marrow (BM) plasma cells < or =40% at diagnosis (P=0.0243) and recovery of ALC > or =1000/mm(3) by day +23 (P=0.0156). Positive predictors for progression-free survival (PFS) were BM plasma cells < or =40% at diagnosis (P=0.0134) and recovery of ALC > or =1000/mm(3) by day +23 (P=0.0243). Absolute neutrophil count > or =1000/mm(3) on day +12 was marginally significant for OS and PFS (P=0.0821 and P=0.1153, respectively). Multivariate analysis showed that ALC > or =1000/mm(3) on day +23 independently predicted OS (P=0.031) and prolonged PFS (P=0.011), and that serum beta2-microglobulin was marginally significant for prolonged OS (P=0.066). In conclusion, ALC recovery was an independent predictor of both OS and PFS in MM.