Acute myeloid leukaemia M0: haematological, immunophenotypic and cytogenetic characteristics and their prognostic significance: an analysis in 241 patients

Haematological, immunophenotypic and cytogenetic characteristics were analysed in 241 patients with acute myeloid leukaemia (AML) M0, including 58 children. Children < 3 years and adults between 60 and 70 years of age were most frequently affected. Immunophenotyping showed a heterogeneous phenotype. Anti-myeloperoxidase was positive in about half of the patients. Cytogenetic data were available from 129 (54%) patients. A normal karyotype was found in only 24%. Most of the abnormalities were unbalanced and the chromosomes 5, 7, 8 and 11 were the most frequently affected. Survival data were available from 152 treated patients (63%). The median overall survival for all patients was 10 months, 20 months for children (n = 36), 10 months for the young adult group (n = 50) and 7 months for the elderly patients (n = 66) (P = 0.09). Karyotype was not a prognostic factor influencing survival. AML M0 shows the immunological characteristics of early progenitor cells, but the expression of the different markers and cytogenetic abnormalities is heterogeneous. The prognosis is poor compared with other de novo AML and similar to that of AML with multilineage dysplasia or AML following myelodysplastic syndromes.     

Trisomy 12 defines a group of CLL with atypical morphology: correlation between cytogenetic, clinical and laboratory features in 544 patients

We have analysed the clinical and laboratory features in 544 patients with chronic lymphocytic leukaemia (CLL) with available cytogenetics and fluorescence in-situ hybridization (FISH) analysis for trisomy 12 in half of them, to examine the correlation between chromosome abnormalities and clinical or laboratory parameters. Five chromosome groups were defined: (1) trisomy 12 (18%), detected as the sole abnormality or associated with other changes; (2) del(13)(q12–14) (7%); (3) other abnormal karyotypes (20%); (4) normal karyotype (41%); and (5) no divisions (14%). There were no differences in the age distribution between the five groups. Clinical stages (Binet) were: A (74%), B (12%) and C (14%). Stage A was common in cases with del(13q)(82%), normal (84%) and other abnormal karyotypes (74%), whereas it was less common in trisomy 12 cases (64%) and those with no divisions (48%). Typical CLL morphology was found in 83% of cases; 10% had more than 10% prolymphocytes (CLL/PL) and 7% had other atypical features. CLL with trisomy 12 was the only group with a high frequency of either CLL/PL (31%) or atypical morphology (24%). Atypical morphology and CLL/PL were even more frequent when trisomy 12 was associated with other chromosomal abnormalities (70% v 46%). The incidence of cases with CLL/PL and other atypical morphology was significantly lower in the other chromosome groups ( P <0.001. There were no differences in immunophenotype among the various groups except for a higher frequency of stronger Smlg and FMC7 expression in cases with trisomy 12, particularly those with CLL/PL and other atypical morphology. Our findings confirm that trisomy 12 defines a subgroup of CLL with more frequent atypical morphology, including CLL/PL, stronger SmIg and FMC7 expression, more advanced stages (B and C in 18%) and possibly worse prognosis.     

Blast cells in child and adult AML: comparative study of morphocytochemical, immunological and cytogenetic characteristics

Bone marrow blast cells of 174 child and 188 adult patients with AML were examined and characterized in terms of their FAB type, immunological phenotype (102 children, 123 adults) and karyotype (69 children, 95 adults). The incidence of FAB variants of AML proved similar in children and adults. In patients under 15 and over 60, peroxidase activity in myeloblasts was lower than in middle-aged patients. Similar rates of HLA-Dr, Thy-1, CD11a, T-cell antigens, CD19, Gly-A and Eb antigens were found in cells of child and adult patients. The frequency of CD11b, CD38 and CD10 antigen expression on blast cells was higher in children than in adults. Abnormal blast karyotype was noted in 81.8% of children and 73.7% of adults. Translocation (8;21) was usually found in cases of M2 type (82%), significantly more frequently in children, predominantly in the group aged 6-10. t(15;17) was detected in all age groups only in M3 type of cells (86%), t(9;22) occurred more frequently in adults than in children; t(11q23) incidence rates were somewhat higher in children than in adults. Three cases of AML in children are described with deletion of chromosome 5 in their leukaemic cells. The data obtained indicate different biological characteristics of blast cells in children and adults. It is likely that haemopoietic cell involvement in children under 2 years and adult patients over 60 occurs at earlier stages than in middle-aged patients.     

The clinical and biological features of a series of immunophenotypic variant of B‐CLL

Objectives: To describe the clinical and biological features of a series of immunophenotypic variant of B‐CLL (v‐CLL) characterised by intermediate RMH score, in the absence of t(11;14)(q13;q32) in FISH analysis in comparison with a series of typical CLL. Methods: We studied the clinical and biological features of 63 cases of v‐CLL and 130 cases of CLL. Results: We observed significant differences in terms of age <70 yr (P < 0.001), lymphocytosis <20 × 10⁹/L (P < 0.001), lymphocyte doubling time ≤12 months (P = 0.02), high serum β2‐microglobulin levels (P < 0.001) and splenomegaly (P = 0.002); CD38, CD49d, CD1c were more expressed in v‐CLL, CD43 in CLL (P < 0.001). IgV_H mutation and trisomy 12 were more frequent in v‐CLL group (P = 0.001; P < 0.001); del13q14 in CLL (P = 0.008). Gene expression profiling of nine v‐CLL and 60 CLL indicated that the atypical group presented a specific molecular pattern. After a median follow‐up of respectively, 55 (4–196) and 60 months (6–180), 25/42 patients with v‐CLL (48%) and 55/93 patients with CLL (59%) were treated. Time to treatment was significantly shorter in IgV_H‐mutated v‐CLL vs. mutated CLL (P = 0.006). The median overall survival was worse in v‐CLL‐mutated cases (P = 0.062). Conclusion: v‐CLL should be identified and dealt with separately from classic CLL. In particular, the prognostic markers that are routinely used to characterise classical B‐CLL should not be interpreted as having the same meaning.     

B-cell lymphoma associated with haemophagocytic syndrome: a clinical, immunological and cytogenetic study

B-cell lymphoma associated with haemophagocytic syndrome (HPS) is extremely rare in Western countries but has recently been increasingly reported in Asian countries. We describe seven patients with B-cell lymphoma associated with HPS, six males and one female, age range 41-82 years (median 63 years). All patients had fever and splenomegaly, and six of the seven patients had hepatomegaly with no associated lymphadenopathy. The bone marrow showed haemophagocytosis and an infiltration of lymphoma cells. All patients showed increased levels of lactate dehydrogenase, C-reactive protein, ferritin and soluble interleukin-2 receptor. Lymphoma cells were positive for CD19. CD20 and surface immunoglobulin in all patients examined, and positive for CD5 in four of seven patients. Cytogenetic analyses of bone marrow cells showed a complex structural abnormality including chromosome 14q32 in two patients, 19q13 in three patients and deletion of the terminal part of 8p21 in six patients. The prognosis was poor; only two of the seven patients have survived in complete remission with a median survival of 11 months. These data suggested that B-cell lymphoma associated with HPS might constitute a distinct biological and clinical disease entity. Abnormality of chromosome 19q13 and loss of 8p21 might be involved in the pathogenesis of this disease.     

Erythroblastic transformation of chronic granulocytic leukemia: a clinical and cytogenetic case study

A 33-year-old male with Philadelphia chromosome-positive chronic granulocytic leukemia developed an erythroblastic transformation of the disease that was characterized cytogenetically by marked hyperdiploidy with multiple numerical and structural abnormalities. It is suggested that such bizarre chromosome abnormalities may be helpful in the diagnosis of this variety of transformation.     

The t(14;19)(q32;q13)-positive small B-cell leukaemia: a clinicopathologic and cytogenetic study of seven cases

The t(14;19)(q32;q13), involving the BCL3 locus at chromosome 19q13 and the immunoglobulin heavy chain gene at 14q32, is a rare recurrent cytogenetic abnormality identified in B-cell neoplasms, most of which have been classified as chronic lymphocytic leukaemia (CLL) in the literature. We describe the clinicopathological, immunophenotypic and cytogenetic findings in seven patients with B-cell neoplasms associated with t(14;19)(q32;q13). There were five men and two women, with a median age of 48 years (range 33-68). All had absolute lymphocytosis, six had lymphadenopathy, and one had splenomegaly. Lymphocytes in blood and bone marrow aspirate smears were predominantly small and cytologically atypical. Flow cytometric immunophenotyping showed an atypical immunophenotype with low CLL scores. The growth pattern in bone marrow biopsy specimens was interstitial to diffuse; immunohistochemical stains were positive for bcl3 and negative for cyclin D1. Lymph node biopsy specimens of two patients revealed total architectural effacement by neoplasm with proliferation centres. In addition to t(14;19), cytogenetic studies demonstrated trisomy 12 in five patients. These results suggest that B-cell neoplasms with the t(14;19)(q32;q13) present frequently as leukaemia composed of small B-lymphocytes and share many features with CLL. However, these neoplasms also differ from CLL cytologically and in their immunophenotype.     

Cytogenetic abnormalities and their prognostic significance in idiopathic myelofibrosis: a study of 106 cases

The prognostic significance of cytogenetic abnormalities was determined in 106 patients with well-characterized idiopathic myelofibrosis who were successfully karyotyped at diagnosis. 35% of the cases exhibited a clonal abnormality (37/106), whereas 65% (69/106) had a normal karyotype. Three characteristic defects, namely del(13q) (nine cases), del(20q) (eight cases) and partial trisomy 1q (seven cases), were present in 64.8% (24/37) of patients with clonal abnormalities. Kaplan-Meier plots and log rank analysis demonstrated an abnormal karyotype to be an adverse prognostic variable ( P  < 0.001). Of the eight additional clinical and haematological parameters recorded at diagnosis, age ( P  < 0.01), anaemia (haemoglobin ≤10 g/dl; P  < 0.001), platelet (≤100 × 10⁹/l, P  < 0.0001) and leucocyte count (>10.3 × 10⁹/l; P  = 0.06) were also associated with a shorter survival. In contrast, sex, spleen and liver size, and percentage blast cells were not found to be significant. Multivariate analysis, using Cox's regression, revealed karyotype, haemoglobin concentration, platelet and leucocyte counts to retain their unfavourable prognostic significance. A simple and useful schema for predicting survival in idiopathic myelofibrosis has been produced by combining age, haemoglobin concentration and karyotype with median survival times varying from 180 months (good-risk group) to 16 months (poor-risk group).     

Analysis of clinical characteristics and prognostic factors of multiple myeloma: a retrospective single-center study of 787 cases

Objective: This study aims to explore the clinical features of multiple myeloma (MM) and the influence of various prognostic factors on survival.

Methods: A retrospective analysis, consisting of clinical characteristics analysis and laboratory examinations, was performed on 787 MM patients. Clinical and laboratory parameters were analyzed by multivariate process and compared across different groups.

Results: Of the 787 patients enrolled (median age, 61 years old, range 29–89 years old), 491 (62.4%) were male. Two most common complaints were bone pain (51.2%) and fatigue (48.0%). Anemia (hemoglobin (Hb) ≤100?g/L in female, Hb ≤110?g/L in male) was present initially in 69.4% patients. IgG was the most common type (46.6%). 52.2% of the patients were diagnosed on stage IIIA according to Durie–Salmon (D–S) system, 44.6% are on stage III according to International Staging System (ISS). Multivariate analysis suggested that age, serum calcium, LDH, percentage of abnormal plasma cells in bone marrow were all independent prognostic factors for OS.

Conclusion: The MM patients in China are relatively younger, have higher rate on stage III according to D–S system. Older age, high serum calcium, high LDH, high percentage of abnormal plasma cells in bone marrow were highly related to poor prognosis.     

Comparative study on the clinical characteristics of local cases of COVID-19 and imported cases from abroad: A retrospective cohort study

It is presently unknown whether imported cases of the 2019 coronavirus disease (COVID-19) have different characteristics when compared with local cases. To compare the clinical characteristics of local cases of COVID-19 in China compared with those imported from abroad.This was a retrospective study of confirmed cases of COVID-19 admitted at the Beijing Ditan Fever Emergency Department between February 29^th, 2020, and March 27^th, 2020. The clinical characteristics of the patients were compared between local and imported cases.Compared with local cases, the imported cases were younger (27.3 ± 11.7 vs. 43.6 ± 22.2 years, P < .001), had a shorter interval from disease onset to admission (1.0 (0.0–2.0) vs 4.0 (2.0–7.0) days, P < .001), lower frequencies of case contact (17.4% vs 94.1%, P < .001), fever (39.1% vs 82.4%, P < .001), cough (33.3% vs 51.0%, P = .03), dyspnea (1.9% vs 11.8%, P = .01), fatigue (7.5% vs. 27.5%, P = 0.001), muscle ache (4.7% vs. 25.5%, P < 0.001), and comorbidities (P < .05). The imported cases were less severe than the local cases, with 40.4% versus 5.9% mild cases, 2.8% versus 15.7% severe cases, and no critical cases (P < .001). The length of hospital stay was longer in imported cases than in local cases (32.3 ± 14.5 vs 21.7 ± 11.2 days, P < .001). The imported cases showed smaller biochemical perturbations than the local cases. More imported cases had no sign of pneumonia at computed tomography (45.0% vs 14.9%, P = .001), and none had pleural effusion (0% vs 14.9%, P < .001).Compared with local cases, the imported cases of COVID-19 presented with milder disease and less extensive symptoms and signs.     

Cytochemical, immunophenotypic and ultrastructural characterization of acute leukemias: a prospective study of fifty cases: haematological malignancy

Cytochemistry and immunophenotyping are established methods in the diagnosis of most leukemias but the role of electron microscopy in diagnosis, apart from understanding the cellular morphology is less studied. We present here 50 cases of acute leukemias that were studied for morphology, conventional cytochemistry, immunophenotyping and transmission electron microscopy (TEM), including ultrastructural cytochemistry using myeloperoxidase (MPO) and platelet peroxidase activity. TEM morphology using ultrastructural cytochemistry helped in definitive typing in one mixed lineage leukemia case, one AML-M5b, one AML-M6b and one microgranular variant of APML. Thus, ultrastructural studies may be useful in accurate diagnosis of biphenotypic leukemia and further classification of acute leukemias. Also, in cases with hypercellular marrow and with associated myelofibrosis, where the marrow aspirate gives low cell count, ultrastructural studies are a valuable aid to arriving at an accurate diagnosis.     

Cytochemical,immunophenotypic and ultrastructural characterization of acute leukemias: A prospective study of fifty cases

Cytochemistry and immunophenotyping are established methods in the diagnosis of most leukemias but the role of electron microscopy in diagnosis, apart from understanding the cellular morphology is less studied. We present here 50 cases of acute leukemias that were studied for morphology, conventional cytochemistry, immunophenotyping and transmission electron microscopy (TEM), including ultrastructural cytochemistry using myeloperoxidase (MPO) and platelet peroxidase activity. TEM morphology using ultrastructural cytochemistry helped in definitive typing in one mixed lineage leukemia case, one AML-M5b, one AML-M6b and one microgranular variant of APML. Thus, ultrastructural studies may be useful in accurate diagnosis of biphenotypic leukemia and further classification of acute leukemias. Also, in cases with hypercellular marrow and with associated myelofibrosis, where the marrow aspirate gives low cell count, ultrastructural studies are a valuable aid to arriving at an accurate diagnosis.     

Various distinctive cytogenetic abnormalities in patients with acute myeloid leukaemia aged 60 years and older express adverse prognostic value: results from a prospective clinical trial

Diagnostic cytogenetic abnormalities are considered important prognostic factors in patients with acute myeloid leukaemia (AML). However, the prognostic assessments have mainly been derived from patients with AML aged <60 years. Two recent studies of AML patients of 60 years and older proposed prognostic classifications with distinct discrepancies. To further study the prognostic value of cytogenetic abnormalities in this patient population, we have evaluated cytogenetic abnormalities in a series of 293 untreated patients with AML aged 60 years and older, included in a randomised phase 3 trial, also in relation to patient characteristics and clinical outcome. The most frequently observed cytogenetic abnormality was trisomy 8 (+8), in 31 (11%) patients. Abnormalities, such as -5, 5q-, abn(17p) and abn(17q), were almost exclusively present in complex karyotypes. A relatively favourable outcome was only observed in five patients with core-binding factor abnormalities t(8;21) and inv(16)/del(16)/t(16;16). However, most of the other evaluated cytogenetic abnormalities, such as 5q-, -7, +8, abn(17p), abn(17q), and complex aberrations expressed a more adverse prognosis when compared with patients with AML aged 60 years and older with a normal karyotype. Large studies to confirm the prognosis of individual cytogenetic aberrations are warranted.     

Pathogenesis, prevalence, and prognostic significance of cytopenias in chronic lymphocytic leukemia (CLL): a retrospective comparative study of 213 patients from a national CLL database of 1,518 cases

Utilizing the database of the Israeli CLL Study Group, we investigated the prevalence and prognostic significance of anemia and thrombocytopenia in patients with chronic lymphocytic leukemia (CLL). Of 1,477 patients, 113 had anemia and thrombocytopenia associated with “infiltrative” marrow failure, median survival of 41 and 86 months, respectively. Autoimmune cytopenias were diagnosed in 100 patients, autoimmune hemolytic anemia (AIHA) in 80, and immune thrombocytopenia (ITP) in 31, while 11 had both co-existent. Median survival of patients with AIHA and ITP, from CLL diagnosis, was 96 and 137 months, respectively, but 29 and 75 months from onset of cytopenia. Patients with AIHA from the time of CLL diagnosis had a significantly shorter survival than those without anemia (p?<?.0001). Survival was similar for patients with AIHA or anemia due to “infiltrative” bone marrow failure (p?=?.44). The presence of positive antiglobulin test even without hemolysis was associated with worse outcome. Overall survival of patients with ITP and those without cytopenias (p?=?0.94) were similar. In conclusion, laboratory or clinical evidence of AIHA has a significant negative impact on the survival of patients with CLL. Outcome for cases with ITP and patients without cytopenias was similar.     

Cell surface expression of CD25, CD54, and CD95 on B- and T-cells in chronic lymphocytic leukaemia in relation to trisomy 12, atypical morphology and clinical course

BACKGROUND: Surface antigen expression can be used to define subgroups of patients with different clinical courses in chronic lymphocytic leukaemia of the B-cell type (CLL). PURPOSE-METHODS: To study the clinical significance of functional markers linked to proliferation (CD25), adhesion (CD54), and apoptosis (CD95) on B- and T-cells in 68 patients with CLL using dual colour flow cytometry (FCM). RESULTS: The mean proportion of CD19+ B-cells expressing CD25 was significantly higher in CLL patients compared to controls (P=0.02), while CD54+ and CD95+ B-cells did not differ significantly. In CLL with atypical morphology and in patients with trisomy 12, the mean percentage of CD25+ B-cells was lower than in typical CLL (P<0.02) and in patients with disomic tumor cells (P<0.03). Patients with 30% of CD25+ B-cells had a shorter median time to treatment than CD25-negative cases (P=0.01). A low CD54 expression was associated with a prolonged median time to treatment (P=0.004), low WBC counts (P<0.05), and low S-LDH (P=0.03). A high CD95 expression was correlated with elevated S-LDH (P=0.02) and a finding of lymphadenopathy (P=0.02). In individual patients there was a strong correlation between B- and T-cell expression of CD25 (P<0.0001), CD54 (P=0.0002), and CD95 (P=0.0002), respectively. CONCLUSIONS: CD25 and CD54 expression on CD19+ cells seems to give prognostic information. The strong correlation between the expression of CD25, CD54 and CD95 on B-and T-cells suggests that the expression of these antigens is not an inherent characteristic of the malignant B-cell clone.     

The clinical features and prognostic outcomes of primary mediastinal yolk sac tumors: A retrospective analysis of 15 rare cases from multiple centers

Primary mediastinal yolk sac tumors (PMYSTs) are a rare occurrence. As such, the clinicopathological features, treatment, and prognosis, of this disease still remain unclear. In this study, we aimed to provide further information relating to this rare malignancy in order to facilitate the creation of more specific clinical guidelines for the diagnosis and treatment of patients with PMYSTs.In this retrospective study, we recruited 15 patients who had been diagnosed with PMYST from four medical institutions to create a population-based cohort. We then used Kaplan-Meier analysis and the log-rank test to investigate and compare overall survival (OS) and progression-free survival (PFS).A total of 15 cases were identified. The mean age was 27.3 years (range: 19–34 years). The estimated 1- and 2-year PFS rates were 66.7% and 60.0%, respectively. The 1- and 2-year OS rates were both 73.3%. Computer tomography scans revealed tumors were located in the anterior middle mediastinum (5 cases), the anterior superior mediastinum (1 case), the left anterior mediastinum (3 cases), and the right anterior mediastinum (6 cases). Of the 15 patients receiving extended resections, the majority (40.0%) underwent tumor resection, partial pericardiotomy, pulmonary wedge resection, and mediastinal lymphadenectomy. R0 resections were achieved in eleven patients. Four patients underwent R2 resection and experienced postoperative complications, including pneumonia (2 cases), atelectasis (1 case), and bronchopleural fistula (1 case). Four patients developed postoperative lung metastasis. Three patients died due to progressive diseases. Disease recurred in all patients at a median of 8.0 months (range: 6.0–11.0 months).PMYST is a rare but highly malignant tumor with a poor prognosis. Tumor resection, with optimal extended surgical management, may provide patients with the best chance of a cure although postoperative complications relating to the pulmonary systems should be treated with caution.     

Minimally differentiated acute myeloid leukaemia (AML-MO): cytochemical, immunophenotypic and cytogenetic analysis of 19 cases

Summary. We describe our experience in the identification of 19 cases of AML-MO categorized among 200 consecutive AML cases. Leukaemic cells from our cases were morphologically marked by agranuler basophilic cytoplasm, finely dispersed chromatin and prominent nucleoli. In two cases heavily vacuolated and monocytoid-shaped blasts were also observed. Cytochemistry (MPO, SBB, αANAE, αNBE, NASDCAE, AP, PAS) was negative in 14 cases, five cases expressing a very faint cytoplasmic positivity for αNBE (not exceeding 30% of the blasts) and αANAE (not exceeding 41%) which was sodium fluoride resistant. In these five cases other monocytic markers (e.g. CD14) were not in favour of myelomonocytic differentiation. All the cases were anti-MPO positive at frequency > 10%. Phenotypic analysis also revealed myeloid features with all the patients having at least one myeloid antigen (CD13, CD33, CD15), Tdt was expressed in nine cases and CD7 in six cases. All cases but one were positive for CD34. Cytogenetic analysis, performed in 16 cases, showed no adequate growth in two cases and no consistent abnormality in four; among the remaining 10 cases no consistent abnormality was observed, the most common finding was trisomy 8 (two cases) and 4 (two cases) and aberrations of chromosomes 2, 3, 5, 7, 9, 12 and 21. No cases of (t9;22), Ph chromosome were observed. Interestingly three out of five patients with faint αNBE/αANAE positivity relapsed as typical M4 (one case) or M5a (two cases).     

Trisomy 3 in marginal zone B-cell lymphoma: a study based on cytogenetic analysis and fluorescence in situ hybridization

Trisomy 3 represents the most frequent and consistent chromosomal abnormality characterizing the recently defined entity marginal zone B-cell lymphoma (MZBCL). By cytogenetic analysis and/or fluorescence in situ hybridization (FISH) on interphase nuclei we found an increased copy number of chromosome 3 in 22/36 (61%) successfully analysed cases, including 8/12 cases with extranodal MZBCL, 8/13 cases with nodal MZBCL, and 6/11 patients with splenic MZBCL. Sensitivity of interphase cytogenetics was somewhat higher than that of conventional cytogenetic investigation. Structural chromosomal changes involving at least one chromosome 3 were seen in 11/20 cases with an increased copy number of chromosome 3: +del(3)(p13) was demonstrated in three cases, and was the sole chromosomal abnormality in one of them; +i(3)(q10) was seen in two other patients; and rearrangements involving various breakpoints on the long arm of chromosome 3 were found in the remaining cases. FISH on metaphase spreads confirmed these structural abnormalities and additionally showed two unexpected translocations involving chromosome 3. We conclude that: (1) trisomy 3 occurs in a high proportion of extranodal, nodal and splenic MZBCL; (2) FISH on interphase nuclei is an additional and sensitive tool in detecting an increased copy number of chromosome 3 in MZBCL; (3) additional structural abnormalities involving the long arm of chromosome 3 are frequent but non-recurrent and are perhaps secondary changes; and (4) abnormalities such as +del(3)(p13) and +i(3)(q10) suggest that genes located on the long arm of chromosome 3 are of particular importance in the pathogenesis of MZBCL.