Clonal identification in acute lymphoblastic leukemia.

In a case of acute lymphoblastic leukemia, two distinct types of leukemia blast cells could be identified throughout the course of the disease. The initially dominant type of blast cell was sensitive to chemotherapy; the other was drug-resistant, gradually becoming dominant as the disease progressed. The cell types could be clearly separated by their morphologic and surface membrane marker characteristics. The same chromosomal constitution was present in both types of blast cells, indicating a common clonal origin. Additional chromosomal abnormalities were present in the later stages of the disease, demonstrating that a distinct subclone had proliferated. This study illustrates that in some cases of acute leukemia, disease relapse is caused by growth of drug-resistant subclones that may be clearly identified by changes in morphology and surface membrane marker characteristics.     

Acute lymphoblastic leukemia in the elderly. A twelve-year retrospective, single center study

Acute myeloid leukemia in elderly patients is a well-studied disease, while only a few studies on acute lymphoid leukemia (ALL) in elderly patients have been reported and their results are not encouraging. The aims of the present study were to review the characteristics of acute lymphoblastic leukemia developing in patients aged over 65 years old during a twelve-year period at our Institution and to analyze the clinical and laboratory characteristics.     

Biological characteristics of newly diagnosed poor prognosis acute myelogenous leukemia

A pilot study was conducted of the biological characteristics of the leukemia cells of newly diagnosed patients with poor prognosis acute myelogenous leukemia (AML). This study included measurements of the pretherapy proliferative rate of the leukemia cells in vivo, assessment of differentiation in vivo during remission induction therapy, and the level of expression of the fms, myc, and IL1β genes in pretherapy leukemia cells. Short cell cycle times were characteristic of the best prognostic category and were associated with a rapid reduction in marrow leukemia cells in cytosine arabinoside (araC)-sensitive patients. Expression of c-fms was associated with rapid reduction in marrow leukemia cells during araC therapy and with a successful treatment outcome. Expression of the IL1β gene was associated with short remissions. These studies suggest that when compared to newly diagnosed standard prognosis AML, the leukemia of poor prognosis patients is more likely to exhibit long cell cycle times, low levels of fms expression, and is less likely to be associated with myeloid differentiation during remission induction therapy. © 1993 Wiley-Liss, Inc.     

白塞病合并急性白血病五例临床分析

目的 研究白塞病(BD)合并急性白血病的临床特征,探讨两者间的关系.方法 选取5例BD病合并急性白血病病例进行临床分析.结果 5例患者临床表现按发生率多少分别为:口腔溃疡和发热(5例)、皮肤损害(3例)、外阴溃疡(3例)、眼炎(3例)、关节痛(4例)、肠道溃疡及消化道出血(1例).本组患者在发生急性白血病前近期内郁有不同程度的外周血象改变,并且有免疫抑制剂使用史.合并的白血病:急性粒细胞白血病3例,急性单核细胞白血病1例、浆细胞白血病1例.5例患者在1年内均死亡.结论 从发病诱因、临床表现、药物使用等方面分析,BD与白血病之间存在有一定的相关性.     

Acute myelomonocytic leukemia: an immunoelectron microscopic study

Acute myelomonocytic leukemia (M4; French-American-British classification) is light microscopically defined as the leukemia constituting leukemic cells in both granulocytic and monocytic lineages. Therefore, the characteristics of M4 have not been fully elucidated. The author previously indicated that normal neutrophilic granulocytes could be ultrastructurally differentiated from normal monocytes by the double staining of lactoferrin and lysozyme. In this investigation, the ultrastructural localization of both proteins were observed in order to make the outline of M4 clear. The leukemic cells in acute myeloid leukemia (M2) were also examined in comparison with those in M4. The leukemic cells in M4 showed the double stainability of lactoferrin and lysozyme, and the positive reactions were localized in the cytoplasmic matrix and in the granules. The staining pattern was similar to that in M2. The coexistence of lactoferrin and lysozyme in the leukemic cells in M4, which has ultrastructurally the monocytic characteristics, implied that the leukemic cells also possess the characteristics of the cells in the granulocytic lineage. This suggests that the presence of the various leukemic cells in the granulocytic lineage. This suggests that the presence of the various leukemic cells signifies the diversely abnormal maturations in vivo of the monocytes/granulocytes precursor cell and that M4 consists of not two kinds of distinguishable cells of granulocytic and monocytic lineages but various consecutive cells based on a malignant transformation of the precursor cell.     

Thromboembolic and bleeding complications in acute leukemia

The risk of both thromboembolic and bleeding complications is high in acute leukemia. This double hazard has a significant negative impact on the morbidity and mortality of patients with this disease. The clinical manifestations of both complications show special features specific to the form of acute leukemia. Recognition of these characteristics is important in the diagnosis and management of acute leukemia. In this article, several additional issues are addressed, including the features of bleeding and thrombosis in acute promyelocytic leukemia, the current understanding of the leukostasis syndrome and the iatrogenic complications including catheter-associated thrombosis, and the adverse effects of therapeutic agents used in acute leukemia. As regards the bleeding complications, thrombocytopenia is a major cause. Corrective measures, including recent guidelines on platelet transfusions, are provided.     

T-lymphocyte variant of hairy-cell leukemia.

Immunohematologic studies on cells from a patient with the clinicopathologic syndrome of hairy-cell leukemia showed that the neoplastic cells had receptors for sheep erythrocytes and therefore had human T-lymphocyte characteristics. The leukemic cells did not have the membrane receptors or immunoglobulin markers of B lymphocytes or monocytes nor did they synthesize immunoglobulin. A lymphoid cell line established in vitro from the cells had the same T-lymphocyte characteristics. The lymphoid cell line is positive for tartrateresistant acid phosphatase, forms rosettes with untreated sheep erythrocytes, and reacts with an anti-T-lymphocyte antiserum. Thus the syndrome of hairy-cell leukemia may occasionally result from the neoplastic proliferation of T-lymphocytes as well as from the more usual B-lymphocyte form. This situation is analogous to that described previously in chronic lymphocytic leukemia and other lymphoproliferative disorders.     

Acute Megakaryoblastic Leukemia Harboring a Subclone Expressing BCR-ABL1 Fusion Gene Product

Acute myeloid leukemia (AML) with BCR-ABL1, also termed Philadelphia chromosome-positive AML (Ph+ AML), is a rare leukemia subtype classified by the World Health Organization in 2016. The characteristics of Ph+ AML have not been fully identified yet. We herein report a patient with Ph+ AML who phenotypically exhibited megakaryoblastic characteristics, FAB:M7 and harbored a subclone expressing BCR-ABL1 gene fusion products. This case suggests that BCR-ABL1 was acquired as a subclone due to a secondary event that might have occurred late during leukemia evolution. Our findings may aid in deciphering the mechanism underlying Ph+ AML development in future studies.     

Clinical and biological characteristics of adult biphenotypic acute leukemia in comparison with that of acute myeloid leukemia and acute lymphoblastic leukemia: a case series of a Chinese population

Background

Biphenotypic acute leukemia is a rare disorder that is difficult to diagnose. It displays features of both myeloid and lymphoid lineage. There is still a lack of studies in biphenotypic acute leukemia in a Chinese population. We present here a comprehensive investigation of the clinical and biological characteristics, and outcome of biphenotypic acute leukemia in our hospital in over a seven year period.

Design and Methods

We retrospectively analyzed 452 adult acute leukemia patients diagnosed according to French-American-British (FAB) classification and biphenotypic acute leukemia diagnosed according to European Group for the Immunological Characterization of Leukemias (EGIL) classification, respectively. Biological characteristics, response to treatment, and outcome were examined in biphenotypic acute leukemia patients and compared with that in acute myeloid leukemia and acute lymphoblastic leukemia patients with complete follow-up profiles diagnosed in the same period.

Results

Of 452 acute leukemia patients, 21 cases (4.6%) were diagnosed as biphenotypic acute leukemia. Among them, 14 (66.7%) were B lymphoid and myeloid, 5 (23.8%) were T lymphoid and myeloid, one (4.8%) was T/B lymphoid and one (4.8%) was trilineage differentiation. When compared with acute myeloid leukemia and acute lymphoblastic leukemia, patients with biphenotypic acute leukemia showed significantly higher incidence of CD34 antigen expression, unfavorable karyotypes, and extramedullary infiltration (p<0.05). In this cohort of patients with biphenotypic acute leukemia, t(9;22) was the most common abnormality in chromosome structure. The median disease-free survival and overall survival in biphenotypic acute leukemia patients was five months and ten months, respectively, significantly shorter than those in acute myeloid leukemia and acute lymphoblastic leukemia patients (p<0.05).

Conclusions

The prognosis of biphenotypic acute leukemia patients is poor when compared with de novo acute myeloid leukemia or acute lymphoblastic leukemia. Biphenotypic acute leukemia patients showed a much higher incidence of CD34 antigen expression, complex abnormal karyotype, extramedullary infiltration, relapse, and resistance to therapy after relapse.     

Establishment of a human myeloid cell line with trisomy 8 derived from overt leukemia following myelodysplastic syndrome

A human myeloid cell line with trisomy 8 was newly established from overt myelogenous leukemia arising in myelodysplastic syndrome. The cells of this cell line showed immature myelocyte characteristics. The karyotype retained trisomy 8. This cell line could improve understanding of the pathophysiology of myelogenous leukemia with trisomy 8.     

Treatment and outcomes for chronic myelomonocytic leukemia compared to myelodysplastic syndromes in older adults

Prior studies have investigated patients'' characteristics, treatments, and outcomes for older adults with myelodysplastic syndromes, but most failed to distinguish chronic myelomonocytic leukemia. Recognizing potentially important differences between the diseases, we undertook a population-based comparison of baseline characteristics, treatments, and outcomes between older adults with chronic myelomonocytic leukemia and myelodysplastic syndromes. The patients'' data were obtained from Surveillance Epidemiology and End Results registry data from 2001-2005, linked to Medicare claims. Baseline characteristics, treatment (red blood cell transfusions, hematopoietic growth factors, hypomethylating agents, chemotherapy or transplantation), progression to acute myeloid leukemia, and overall survival were compared using bivariate techniques. Multivariate logistic regression estimated differences in treatments received. Cox proportional hazard models estimated the effects of chronic myelomonocytic leukemia relative to myelodysplastic syndromes on progression-free survival. A larger proportion of patients with chronic myelomonocytic leukemia (n=792), compared to patients with myelodysplastic syndromes (n=7,385), failed to receive any treatment (25% versus 15%; P<0.0001), or only received red blood cell transfusions (19.8% versus 16.7%; P=0.037). A larger percentage of patients with chronic myelomonocytic leukemia progressed to acute myeloid leukemia (42.6% versus 15.5%, respectively; P<0.0001), with shorter time to progression. Chronic myelomonocytic leukemia patients had a shorter median survival (13.3 versus 23.3 months; P<0.0001) and lower 3-year survival rate (19% versus 36%; P<0.0001). Adjusted estimates, controlling for baseline characteristics and selected treatments, indicate that chronic myelomonocytic leukemia was associated with an increased risk of progression to acute myeloid leukemia or death (HR 2.22; P<0.0001), compared to myelodysplastic syndromes. In conclusion, chronic myelomonocytic leukemia is less frequently treated in older adults and is associated with worse outcomes, even after controlling for the patients'' baseline characteristics and selected treatments. Our data suggest the need for continued evaluation of the biological differences between these diseases and clinical trials targeting chronic myelomonocytic leukemia.     

In vitro culture of leukemic cells in t(4;11) acute leukemia

In the present study we utilized a semisolid culture system with feeder cells and enriched media to evaluate the growth of acute leukemia associated with the 4;11 chromosomal translocation. We compared growth of t(4;11) leukemia to typical acute nonlymphocytic leukemia (ANL) and acute lymphocytic leukemia (ALL). The two cases of t(4;11) leukemia tested exhibited the highest cloning efficiency of cells tested. The growth characteristics of t(4;11) leukemia were more similar to ANL than ALL.     

Myelogenous Leukemia in the Rat

Observations on growth and other characteristics of subcutaneously transplanted chloroleukemia in non-inbred rats have been described in this report.This chloroleukemia cytologically is an acute or subacute, not chronic, myelogenous leukemia. Because of serious immunologic differences, the experimentalusefulness of subtransferred chloroleukemia is greatly limited. However,myelogenous leukemia in the rat, induced by chemical agents or ionizing radiation, may offer a valuable approach to the study of leukemogenic mechanisms.

Submitted on June 23, 1961 Accepted on August 18, 1961     

A prospective study of the natural history of transient leukemia (TL) in neonates with Down syndrome (DS): Children's Oncology Group (COG) study POG-9481

A unique transient leukemia (TL) has been described in newborns with Down syndrome (DS; or trisomy 21 mosaics). This leukemia has a high incidence of spontaneous remission; however, early death and subsequent development of acute megakaryoblastic leukemia (AMKL) have been reported. We prospectively evaluated 48 infants with DS and TL to determine the natural history and biologic characteristics of this disease, identify the clinical characteristics associated with early death or subsequent leukemia, and assess the incidence of subsequent leukemia. Blast cells associated with TL in DS infants exhibited FAB M(7) morphology and phenotype. Most infants (74%) had trisomy 21 (or mosaicism) as the only cytogenetic abnormality in the blast cells. Most children were able to spontaneously clear peripheral blasts (89%), normalize blood counts (74%), and maintain a complete remission (64%). Early death occurred in 17% of infants and was significantly correlated with higher white blood cell count at diagnosis (P < .001), increased bilirubin and liver enzymes (P < .005), and a failure to normalize the blood count (P = .001). Recurrence of leukemia occurred in 19% of infants at a mean of 20 months. Development of leukemia was significantly correlated with karyotypic abnormalities in addition to trisomy 21 (P = .037). Ongoing collaborative clinical studies are needed to determine the optimal role of chemotherapy for infants at risk for increased mortality or disease recurrence and to further the knowledge of the unique biologic features of this TL.     

Pharmacogenetics of acute lymphoblastic leukemia

PURPOSE OF REVIEW: The outcome in children with acute lymphoblastic leukemia has improved significantly over the past four decades. Current therapy results in event-free survival exceeding 80% for most patients. The development of risk-adapted therapy based on characteristics of the child (age), leukemia (leukocyte count, acquired genetic characteristics) and early response to therapy allows dose intensification for children with higher-risk disease. Much less attention has been given to the role of host variability (pharmacogenetic polymorphism) in determining outcome. This review discusses literature reports in this area and describes some of the challenges facing the field as it moves forward. RECENT FINDINGS: Polymorphisms in many different metabolic pathways have been demonstrated in single gene studies to influence the outcome of acute lymphoblastic leukemia. Challenges arise in establishing the generalizability of observations and interpreting complex gene-gene interactions in multigene pathways. Recent studies also illustrate the importance of correlation of clinical associations with biological mechanisms. SUMMARY: Despite significant progress in the treatment of childhood acute lymphoblastic leukemia, therapy is still unsuccessful in 20% of patients. Further knowledge of and insight into the role of host genetic polymorphisms will improve the results by integrating pharmacodynamic and pharmacogenomic studies in individualizing therapy for children with acute lymphoblastic leukemia.     

Terminal deoxynucleotidyl transferase activities in human blood leukocytes and lymphoblast cell lines: high levels in lymphoblast cell lines and in blast cells of some patients with chronic myelogenous leukemia in acute phase.

Terminal deoxynucleotidyl transferase, an enzyme which catalyzes the polymerization of deoxyribonucleoside triphosphates, elongating oligo- or polydeoxynucleotide chains, but without direction from a nucleic acid template, is thought to be specific for thymus gland and thymus-derived cells. We have confirmed the observations that high levels are characteristic of thymus gland with both human and calf tissue and that elevated levels may be found in some cases of acute lymphocytic leukemia. High levels were also found in human lymphoblast cell lines with T-cell characteristics, and insignificant activity was observed in leukocytes of patients with chronic myelogenous leukemia not in acute blast phase of the disease, chronic lymphocytic leukemia, human B-cells, and normal human blood lymphocytes even after stimulation with phytohemagglutinin. However, high levels (approximately 200 nmoles/hr/10(9) cells) equivalent to those in thymus tissue and lymphoblast cell lines with T-cell characteristics were found in the peripheral blood blast cells of four patients with chronic myelogenous leukemia in an acute blast phase of their disease. One hypothesis that may explain the present results is that in chronic myelogenous leukemia in acute blast phase of the disease the proliferative blast response may not always be myeloblasts but in some cases it may be lymphoblasts.     

Radiation-induced leukemia: lessons from history

Beginning in 1895, with the discovery of x-rays, alpha and beta radiation, uranium, radium, thorium, and polonium, the fascinating story of the beginning of knowledge concerning the existence of ionizing radiation unfolds. This brief history of radiation and leukemia is divided into two main parts: the first 50 years, which deals with the confusion regarding radiation effects and the failure to clearly recognize that exposure to ionizing radiation may induce leukemia. The second part focuses on the last 60 years, when the radiation induction of leukemia was accepted and some progress achieved in understanding the clinical and pathophysiological characteristics of radiation-induced leukemia. Particular attention in this is paid to the effects of radiation on the survivors of Hiroshima and Nagasaki. The discussion in this section also covers some concepts of radiation-induced cell damage and ruminations on unanswered questions.     

Use of fludarabine in the treatment of mantle cell lymphoma, Waldenström's macroglobulinemia and other uncommon B- and T-cell lymphoid malignancies

After initial efforts using fludarabine as a single agent in the treatment of acute leukemia, its activity at lower and safer doses was demonstrated in chronic lymphocytic leukemia (CLL) patients who were refractory or had relapsed from traditional chemotherapies, representing a highly effective therapy for this condition. Fludarabine was also rapidly shown to be beneficial as first-line therapy in CLL. There is now considerable evidence that fludarabine is an effective agent in non-Hodgkin's lymphoma and in combination therapy for acute myeloid leukemia. Further, good responses are achieved when fludarabine-based approaches are used as conditioning regimens prior to transplantation procedures. The actions of fludarabine are not restricted to these settings and its potential role in the treatment of a range of uncommon T- and B-cell lymphoid malignancies is slowly emerging. This review will focus on the characteristics and treatment options for two B-cell disorders, mantle cell lymphoma and Waldenstr?m's macroglobulinemia, with emphasis on the clinical activity of fludarabine. Additionally, the advantages of using fludarabine-containing regimens for a range of other lymphoproliferative conditions will also be discussed. These include B-cell neoplasms such as the CLL variant prolymphocytic leukemia, hairy cell leukemia and mucosa-associated lymphoid tissue-derived lymphomas; the T-cell disorders cutaneous T-cell lymphoma, angioimmunoblastic lymphadenopathy and other rarer T-cell diseases; and aggressive variants of non-Hodgkin's lymphoma including Richter's syndrome.     

Acute leukemia associated with the t(4;11) chromosome rearrangement: ultrastructural and immunologic characteristics

The acute leukemia associated with the t(4;11) chromosome rearrangement is characterized by relatively consistent clinical features: occurrence primarily in young individuals, hyperleukocytosis, and poor response to therapy. This study describes the morphological, ultrastructural, and immunologic characteristics of the leukemic cells from ten patients with this type of leukemia. The morphological features of the leukemic blasts vary from lymphoid-appearing to monocytic. Ultrastructurally and cytochemically, some of the lymphoid-appearing blasts possess features of myeloid origin. The immunologic phenotype is characteristically E- SIg- CALLA- BA-1- BA-2+ HLA-DR+ and TdT+. These findings suggest that the t(4;11)-associated acute leukemia represents a proliferation of an early myeloid progenitor cell.