Absence Of Blasts In Peripheral Blood Research Articles

Characterisation of children and adolescents with acute lymphoblastic leukaemia who presented without peripheral blood blasts at diagnosis.

Of 1003 children with acute lymphoblastic leukaemia (ALL), 147 (14.7%) presented without peripheral blood blasts (PBB). While absence of PBB was not independently associated with survival outcomes when compared to those with PBB, patients without PBB had distinct genetic and clinical characteristics. Notably, we identified a novel genotype-phenotype relationship, in that the patients without PBB had a significantly higher incidence of hyperdiploid B-ALL, accounting for almost half of all patients without PBB (46.9% vs. 22.7%, p < 0.001). Further, absence of PBB was associated with decreased rates of leukaemia involvement of the central nervous system (p < 0.001).

Outcomes of decitabine treatment for newly diagnosed acute myeloid leukemia in older adults​.

We evaluated the outcomes of decitabine as first-line treatment in older patients with acute myeloid leukemia (AML) and investigated the predictors, including a baseline mini nutritional assessment short form (MNA-SF) score, of response and survival. Between 2010 and 2018, 96 AML patients aged 65 and above who received decitabine treatment at 6 centers in Korea were retrospectively evaluated. Response rates, hematologic improvements (HI), progression-free survival (PFS), and overall survival (OS) were analyzed. The median age at diagnosis was 73.9 years, and the median number of decitabine treatments administered to the patients was 4 (range, 1-29). Of 85 patients, 15 patients (17.6%) achieved complete remission (CR) or CR with incomplete blood count recovery. Twelve patients (14.1%) showed partial remission (PR), and 18 (21.2%) demonstrated HI without an objective response. The median PFS and OS were 7.0 (95% confidence interval [CI], 4.9-9.0) and 10.6 (95% CI, 7.7-13.5%) months, respectively. In multivariate analyses, MNA-SF score ≥ 8 and the absence of peripheral blood (PB) blasts were significant predictors for improved PFS and OS. For older patients with newly diagnosed AML, a high MNA-SF score and the absence of PB blasts were independently associated with improved survival.

5‐Azacytidine treatment for relapsed or refractory acute myeloid leukemia after intensive chemotherapy

Despite progress in the understanding of leukemia pathophysiology, the treatment of acute myeloid leukemia (AML) remains challenging. In patients with refractory or relapsed (R/R) AML, the prognosis is still poor and this group is targeted for new drug development. We reviewed the outcome of 47 patients, with R/R AML after at least one course of intensive chemotherapy, treated with 5-azacytidine in three different French institutions. The overall response rate was 38% including complete remission in 21%, partial remission in 11%, and hematological improvement in 6% of cases. Median time to relapse was 6 (range, 1-39) months. Median overall survival was 9 months (not reached by responders vs. 4.5 months for nonresponders patients, P = 0.0001). Univariate analysis identified the absence of peripheral blood blasts and <20% bone marrow blasts as prognostic factors for both overall response and survival, but not age, ECOG/PS, type of AML, cytogenetic, status of the disease, number of previous lines of therapy, previous hematological stem cell transplantation, or white blood cells count. Bone marrow blasts percentage <20% was the only independent prognostic factor identified by multivariate analysis for overall response (P = 0.0013) and survival (P = 0.0324). Six patients in remission could proceed to an allogenic hematological stem cell transplantation. The drug-related grade 3/4 adverse events were hematopoietic toxicities (38%) and infection (32%). In conclusion, this study suggests that a salvage therapy with 5-azacytidine is an interesting option for patients with R/R AML after intensive chemotherapy. Prospective randomized studies are needed to demonstrate a superiority of this approach over others strategies.

A prediction model for complete remission upon reinduction for patients with acute myeloid leukemia after failure of anthracycline and cytarabine standard chemotherapy

The aim of this study was to investigate clinical parameters that might predict complete remission (CR) following reinduction therapy in patients with acute myeloid leukemia (AML). We retrospectively analyzed outcomes in 142 patients who failed to achieve CR with standard anthracycline-plus-cytarabine induction chemotherapy (IND1) and who received the same regimen as a reduction therapy (IND2). The CR rate after reinduction was 54%. Multivariate analysis showed that the presence of peripheral blood (PB) blasts on the day of commencement of IND2 and ≥20% blasts in an interim BM sample taken during IND1 (C1-INT-BM) were independent risk factors for failure of remission. Our scoring system for prediction of CR after reinduction (CRAR score) included a favorable chromosome risk group, absence of PB blasts on the day of commencement of IND2, and ≤21% blasts in the C1-INT-BM. This scoring system predicted that the rates of CR in the four subgroups would be 92.1%, 68.9%, 29.5%, and 7.3%, respectively, in good agreement with observed CR rates. The CRAR scoring model might be associated with the possibility of achieving CR after reinduction, and may be helpful in choosing alternative strategy for AML patients refractory to standard induction chemotherapy, although further prospective validation is required.

Factors associated with achievement and durability of cytogenetic response in patients with chronic myeloid leukemia treated with imatinib

Imatinib mesylate, a selective Bcr-Abl tyrosine kinase inhibitor, has revolutionized the treatment of Bcr-Abl positive chronic myeloid leukemia and become the standard of care for this disease. The aim of this study was evaluation and analysis of cytogenetic response in different intervals and risk groups as well as finding association between pre-treatment characteristics and later probability of achievement of major cytogenetic response. We analyzed a total of 22 adult patients with newly diagnosed Philadelphia positive early chronic phase chronic myeloid leukemia treated at our institution from June 2006 to December 2009. The median follow-up time for patients during treatment with imatinib was 25.7 months (range, 12-42 months). A complete hematologic response was achieved in all of the analyzed patients within 6 months from the start of the treatment. The major cytogenetic response rate was 81.8%, and the complete cytogenetic response rate was 72.7%. The patients with low or moderate relative risk had the rate of complementary achieving major and complete cytogenetic response of 75-90%. A multivariate analysis identified the following independent prognostic factors for achieving major cytogenetic response: the absence of splenomegaly, white blood cell count less than 10 x 10(9)/L, the platelet count less than 450 x 10(9)/L, the presence of less than 5% of bone marrow blasts and basophils, the absence of blasts in peripheral blood, the presence of less than 7% of basophils in peripheral blood. Patients who early achieve complete and major cytogenetic response as well as those with low and moderate relative risk have a higher rate of achieving and maintaining complete cytogenetic response. There are also characteristics of patients before treatment that may indicate the treatment outcome.

Intracranial hypertension following intrathecal administration of liposomal cytarabine

We report a case of cytarabine-induced intracranial hypertension. Liposomal cytarabine, a standard intrathecal chemotherapeutic, is a slow-release formulation of cytarabine produced by encapsulating the aqueous drug solution in spherical 20 lm diameter multivesicular lipid foam particles. With the 50 mg standard adult dose, sustained cytotoxic drug levels can be reached in the CSF over a 14 day period [1–5]. Neurological complications are arachnoiditis, myelitis, epilepsy, cauda equina syndrome, and toxic leukoencephalopathy [4–9]. A 27-year-old man was diagnosed with T-cell acute lymphoblastic leukemia (T-ALL). After a low dose of intravenous (IV) cyclophosphamide and corticosteroids during 5 days, treatment was initiated consisting of cyclophosphamide 1,200 mg/m IV on the first day of chemotherapy (indexed as day 1), vincristin 2 mg IV on days 3-10-17, daunorubicin 45 mg/m IV on days 3–4, asparaginase 10,000 U/m IV on days 3-5-7-9-11-13-15, and oral methylprednisolone 80 mg from day 3 until day 24. Corticosteroids were tapered from day 24 onwards and stopped on day 39. Cerebrospinal fluid (CSF) analysis on day 2 revealed the presence of blast-like cells (in the absence of peripheral blood blasts) (Table 1). A gadolinium-enhanced brain magnetic resonance imaging (MRI) scan did not reveal any abnormalities. On days 2, 13 and 27 liposomal cytarabine was administered intrathecally. CSF analysis on day 27 was strictly normal (Table 1). An ophthalmological evaluation prior to each of these lumbar punctures was negative. On day 28, the patient developed an intense headache and lumbosacral pain associated with nausea, photophobia and sonophobia, and neck flexion rigidity. Mental status examination was normal. On day 28, he was on methylprednisolone 16 mg/d. Computerized tomography (CT) of the brain and CSF analysis (including cultures for bacteria and fungi and Cryptococcus antigen detection) were normal (Table 1). On day 33, the patient complained of diplopia and worsening headache. Clinical examination revealed a left abducens paresis and bilateral papilledema, with an elevated and hyperemic disc, more severe to the right with presence of numerous peripapillary retinal hemorrhages. Contrast-enhanced MRI of the brain and MRI venography were negative. A repeat lumbar puncture on day 34 revealed an elevated opening pressure of 46 mmHg, without other abnormalities (Table 1), leading to a diagnosis of liposomal cytarabine-induced intracranial hypertension. Intrathecal chemotherapy was discontinued, a single evacuating lumbar puncture was performed and acetazolamide was started (3 9 500 mg IV daily for 2 weeks, followed by 3 9 250 mg orally for 5 weeks). The abducens palsy recovered fully. A mild form of papilledema persisted, without visual loss. Six months later the patient was still symptom-free neurologically. Four similar cases of intracranial hypertension following intrathecal administration of liposomal cytarabine, most often after the third or fourth administration, have been reported before, three with acute myeloid leukemia and one with ALL [7–9]. The temporal sequence of events, with onset shortly after the third administration of liposomal cytarabine, and the nearly complete and prolonged recovery following discontinuation of cytarabine and initiation of acetazolamide, strongly argue against a neoplastic origin in S. Lunskens B. Bergmans R. Vandenberghe (&) Department of Neurology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium e-mail: rik.vandenberghe@uz.kuleuven.ac.be

Chronic Myelomonocytic Leukemia (CMML) with More Than 15% of Ring Sideroblasts in Bone Marrow: An Overlapping Disorder Between CMML and Refractory Anemia with Ring Sideroblasts.

Abstract 290The main diagnostic criteria for chronic myelomonocytic leukemia (CMML), a heterogeneous disorder sharing features of myelodysplastic syndromes (MDS) and chronic myeloproliferative disorders, is the existence of a sustained absolute monocyte count in peripheral blood (PB) above 1 × 109/L. On the other hand, the presence of more than 15% ring sideroblasts (RS) in bone marrow (BM) is a well recognized morphological feature of dyserithropoiesis and, in the absence of blasts in PB and less than 5% blasts in BM, is diagnostic of refractory anemia with ring sideroblasts (RARS) with or without multilineage dysplasia. In FAB as well as in WHO classification systems for myeloid neoplasms those cases presenting with both an absolute monocyte count in PB above 1 × 109/L and more than 15% RS in BM are diagnosed of CMML but the preeminence given to the monocyte count in PB over the proportion of RS in BM is not evidence-based. The main purpose of this study was to assess the clinical and biological characteristics and outcome [overall survival (OS) and acute leukemic (AL) evolution] of a series of 77 patients diagnosed of CMML by FAB and WHO criteria who had more than 15% RS in BM at presentation (CMML-RS) and to compare them with those of a series of 417 patients with CMML with less than 15% RS (classical CMML) and those of a series of 178 patients with classical RARS (38 patients with and 140 patients without multilineage dysplasia). Comparisons of proportions and ranks of variables between different groups were performed by chi square or Mann-Whitney-U tests as appropriate. Actuarial curves of OS and risk of AL evolution were built by Kaplan-Meier method and differences between curves compared with log-rank tests. Multivariate analyses of OS and risk of AL evolution were performed by Cox proportional hazards regression method. Patients with CMML-RS had lower hemoglobin level (P=0.008), lower absolute counts of leukocytes (P<0.001), neutrophils (P=0.002), and monocytes (P<0.001), higher platelet count (P<0.001), lower proportion of blasts in PB (P=0.015) and BM (P=0.035), and higher serum level of ferritin (P<0.001) and LDH (P=0.06) than patients with classical CMML. Patients with CMML-RS had significantly better OS than patients with classical CMML (median, 79 mo and 26 mo respectively; P<0.001; Figure) as well as lower risk of AL evolution (cumulative proportion at 5 yr, 7% and 20% respectively; P=0.07). Further, the beneficial prognostic relevance of the proportion of RS in BM on OS was maintained in multivariate analyses (P<0.001). In marked contrast, OS (median, 64 mo; Figure) and risk of AL evolution (cumulative proportion at 5 yr, 9%) of patients with classical RARS were closely similar to those observed in patients with CMML-RS (P>0.90). Patients with classical RARS were more anemic (P=0.001), had lower absolute counts of leukocytes (P<0.001), neutrophils (P=0.01), and monocytes (P<0.001), higher platelet count (P=0.002), lower proportion of blasts in PB (P=0.01) and BM (P<0.001), and lower serum level of ferritin (P=0.01) and LDH (P=0.11) than patients with CMML-RS. To avoid the potential interference in the analyses of disparities in the proportion of blasts in BM in the different groups of patients all the analyses were repeated excluding from all the groups those cases with 5% or more blasts in BM. Fifty-three patients with CMML-RS, 245 with classical CMML, and all 178 with classical RARS were evaluable for these sub-analyses. The results obtained were similar to those in the overall series of patients (data not showed). To sum up, all these results show that the proportion of RS in BM is a much powerful prognostic indicator than absolute monocyte count in PB in CMML and demonstrate that the presence of a proportion of RS greater than 15% in BM in patients with CMML defines a subset of patients that clearly differ in their biological characteristics from classical CMML and classical RARS. CMML-RS has a clinical course very close to that of classical RARS and markedly better than classical CMML. These data strongly suggest that CMML-RS is an overlapping syndrome between CMML and RARS. For clinical purposes patients with >1 × 109 monocytes/L in PB and >15% RS in BM should be better classified as RARS than as CMML. The WHO classification needs to be revisited to account for those findings. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Disease burden may identify patients more likely to benefit from second allogeneic hematopoietic stem cell transplantation to treat relapsed acute myelogenous leukemia

The major cause of failure after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) is disease relapse or progression. We analyzed the outcome of second HSCT for treatment of patients with relapsed, refractory AML/myelodysplastic syndrome (MDS) at our institution. A total of 72 patients were eligible for this analysis. In all, 25 (35%) patients received salvage chemotherapy prior to the second transplant procedure and only two (3%) patients were in complete remission at the time of the second transplant. A total of 20 patients (28%) had low leukemia burden as measured by the absence of peripheral blood blasts and <or=5% blasts in the bone marrow at the time of the second transplant. Although, the overall median survival after the second transplant was 6 months, a subset of patients who had low leukemia burden at the time of the second transplant had a 5-year survival of 25 vs 12% in those with a high leukemia burden. Thus, a second transplant may offer the possibility of long-term disease control in a subset of patients who have a 'low bulk' disease at the time of transplantation.

Effect of circulating blasts at time of complete remission on subsequent relapse-free survival time in newly diagnosed AML

AbstractStandardized criteria for complete remission (CR) in acute myeloblastic leukemia (AML) require the absence of peripheral blood blasts (PBBs). However, MD Anderson (MDA) criteria for CR (CR-MDA), although including the other requirements for CR, have not included the PBB count. We exploit this difference to assess the effect of PBBs at the time of CR-MDA on relapse-free survival (RFS) time. Eighty percent of the 533 patients with newly diagnosed AML or refractory anemia with excess of blasts (RAEB) entering CR-MDA from 1995 to 2000 had no PBBs at time of CR-MDA. Ninety-three percent of the remaining patients, who thus had CR-MDA but not standard CR, had 1% to 5% PBBs at this time. Multivariate analyses, using both conventional and Bayesian approaches, indicated that PBBs had no effect on RFS. For all patients and for the subgroups given and not given granulocyte colony-stimulating factor (G-CSF), the 95% credible interval for the relative risk of failure in the PBB group was nearly centered at 1.0. Thus, our data do not support use of PBBs in defining CR in newly diagnosed AML.