Trilineage Myelodysplasia Research Articles

Acute myeloid leukemia with monosomy 7, ectopic virus integration site-1 overexpression and central diabetes insipidus: A case report.

Central diabetes insipidus (DI) is a rare complication in patients with acute myeloid leukemia (AML), typically occurring in patients with abnormalities of chromosomes 3 or 7. The association between AML with monosomy 7 and DI has been described in a number of studies; however, DI has been rarely reported in cases of ectopic virus integration site-1 (EVI1)-positive AML with monosomy 7. The current study reports a case of AML with monosomy 7 and EVI1 overexpression, with central DI as the initial symptom. The patient was an 18-year-old female who presented with polyuria and polydipsia. Bone marrow aspiration revealed 83.5% myeloperoxidase-positive blasts without trilineage myelodysplasia. The karyotype was 45,XX,-7, and the patient presented monosomy 7 and EVI1 overexpression (-7/EVI1+) without 3q aberration. Treatment with induction therapy was unsuccessful. To the best of our knowledge, this is the second case of DI-AML with -7/EVI1+ and without a 3q aberration. The possible mechanisms associated with EVI1, monosomy 7 and DI were investigated.

A Mouse Model of Telomere Dysfunction Recapitulates Hallmark Features of Human Myelodysplastic Syndrome

Myelodysplastic syndrome (MDS) is a heterogeneous group of hematopoietic neoplastic disorders that are characterized by ineffective myeloid differentiation and dysplasia as well as telomere shortening and accumulated DNA damage in progenitor cells. Less understood is whether DNA damage is the instigator of impaired progenitor cell differentiation and MDS development. Telomerase deficient mice have served as a model system to demonstrate the adverse effects of wide-spread endogenous DNA damage signaling on stem cell function in vivo. In recent studies, we sought to determine whether persistent physiological DNA damage can impair the function of specific hematopoietic lineages by employing the 4-hydroxytamoxifen (OHT)-inducible telomerase reverse transcriptase-estrogen receptor (TERTER) model. For the first time, we demonstrate that late generation TERTER/ER mice with dysfunctional telomeres exhibit hallmark features of MDS, including peripheral blood cytopenias, bone marrow (BM) hyper-cellularity, and an increased myeloid-to-erythroid progenitor ratio in the absence of increased apoptosis. Severe tri-lineage myelodysplasia, and an increase of immature, morphologically abnormal myeloid blasts frequently with pronounced monocytic differentiation were consistent with refractory anemia with excess of blasts (RAEB) or chronic myelo-monocytic leukemia (CMML), a specific sub-group of MDS that is characterized by a high propensity to develop acute myeloid leukemia (AML). Accordingly, approximately 5% of aged TERTER/ER mice progressed to AML, as demonstrated by a marked increase of BM myeloid blasts, and infiltration of myeloid precursors into the splenic white-red pulp architecture, resulting in myeloid sarcoma with the complete effacement of lymphoid follicles. Compared to control mice with intact telomeres, the progenitor compartment of telomere dysfunctional mice shows a significant increase in the number of granulocyte-macrophage progenitors (GMP) with a concomitant loss of the megakaryocyte-erythroid progenitors (MEP) and slight reduction in the number of common myeloid progenitors (CMP), which is consistent with the condition of skewed myeloid differentiation occurring in MDS patients with higher risk of leukemic transformation. Transplantation experiments of long-term hematopoietic stem cells isolated from telomere dysfunctional mice into wild type congenic recipients revealed that the level of donor-derived skewed myeloid differentiation was comparable to that observed at steady state in the same telomere dysfunctional mice before transplantation, suggesting that impaired progenitor differentiation occurred as a result of cell intrinsic defects of telomere dysfunctional hematopoietic cells. In the setting of telomere dysfunction, somatic in vivo and in vitro telomerase reactivation reduced DNA damage signaling and specifically reversed defective differentiation and MDS phenotypes. Unbiased transcriptomic network analyses of CMP with telomere dysfunction revealed profound down-regulation of genes in the mRNA splicing and processing pathways which was rescued by telomerase reactivation, indicating that telomere dysfunction-induced DNA damage response can impact on the expression of genes involved in splicing regulation. RNA-seq analysis of telomere dysfunctional CMP suggested altered splicing activity at the level of exon usage and identified aberrantly spliced variants of genes implicated in chromatin remodeling, and histone modifications. The prominence of aberrantly spliced epigenetic regulators prompted us to hypothesize that there was a link between impaired myeloid differentiation and aberrant splicing patterns as a result of telomere dysfunction-induced repression of splicing components. In conclusion, our studies have revealed an unanticipated link between telomere biology, RNA splicing, and MDS pathogenesis and support the development of strategies designed to modulate the downstream targets of splicing alterations in specific hematopoietic populations. DisclosuresNo relevant conflicts of interest to declare.

Leukemic Presentation of ALK-negative Anaplastic Large Cell Lymphoma in a Patient with Myelodysplastic Syndrome

A 50-year-old woman with a history of aplastic anemia developed cervical lymphadenopathy and atypical lymphocytosis. Atypical cells of lymph nodes were positive for CD3 and CD30 but negative for anaplastic lymphoma kinase (ALK). Bone marrow examination showed trilineage myelodysplasia. She was diagnosed with ALK-negative anaplastic large cell lymphoma (ALCL) with leukemic transformation and myelodysplastic syndrome (MDS) which presumably developed from aplastic anemia. The lymphoma was resistant to intensive chemotherapies, ultimately leading to death. Leukemic presentation of ALK-negative ALCL as an initial manifestation is extremely rare, and the progression of the disease may be influenced by MDS through alteration of immune functions.

Trilineage myelodysplasia and hemophagocytosis associated with systemic lupus erythematosus

Trilineage myelodysplasia and hemophagocytosis associated with systemic lupus erythematosus

Idiopathic Atypical Hemolytic Uremic Syndrome (aHUS) with Trilineage Myelodysplasia

Atypical hemolytic uremic syndrome (HUS) is a heterogeneous group of disorders, with an unexplained pathogenesis. We report here with an interesting case of a 6 years old male child presenting with atypical feature of HUS and bone marrow trilineage myelodysplasia.

Unusual presentations of Visceral leishmaniasis

We report 3 cases of Visceral leishmaniasis, who presented with unusual clinical manifestations. One child was diagnosed as hemophagocytic syndrome; another masqueraded with features of leukemoid changes alongwith hemophagocytosis and trilineage myelodysplasia; the third case presented with pyothorax. All the three patients showed amastigote forms of Leishmania donovani and positive serology (rk39 antigen). They showed complete clinical, hematological and parasitological resolution with Amphotericin B therapy.

De novo AML with trilineage myelodysplasiaの診断と治療戦略

de novo AML with trilineage myelodysplasiaの診断と治療戦略

Pattern of trisomy 1q in hematological malignancies: a single institution experience

An extra copy of 1q usually originates from the translocated unbalanced derivative chromosome, isochromosome, or “jumping translocation.” We report a pattern of partial trisomies and unbalanced whole-arm translocations of 1q in 10 patients: 5 with myelodysplastic syndrome, 3 with acute myeloid leukemia, and a single patient with acute lymphoblastic leukemia and myeloproliferative syndrome. The trisomy of 1q was registered as the sole karyotype aberration in one patient, while it was accompanied by a limited number of additional chromosomal changes in nine patients. These patients are a subset of a larger group of 92 adults carrying a wide variety of chromosome 1 anomalies within a complex cytogenetic context observed over a period between 1994 and 2006 in a panel of 3,786 hematologic patients at the Institute of Hematology in Belgrade. Conventional cytogenetics was supplemented by fluorescence in situ hybridization with a probe specific for the paracentric region of 1q. Whole-arm 1q translocations involved chromosomes Y, 7, 14, 15, 16, and 19. This study suggests that gain of 1q as the sole cytogenetic abnormality may be sufficiently mutagenic to favor leukemogenesis and hematopoietic tissue degeneration (trilineage myelodysplasia).

Elderly Patients with De Novo Acute Myeloid Leukemia (AML): Prognostic Factors in 132 Cases.

The aim was to determine the predictive value of karyotype in 132 patients ≥65 years in a series of 404 cases with de novo AML. 61 females and 71 males with median age 71 years (65–91). FAB subtype were: 14 (10.6%) M0, 21 M1, 37 M2, 14 (10.6%) M3, 16 M4 (only one M4Eo), 21 M5, 8 M6, 1 M7 (vs 4% M0, 25,7% M3 in <65 years p=0.004). The prognostic value of clinical, pathologic and cytogenetic factors was evaluated by Kaplan-Meier estimate and compared by log-rank, Breslow and Tarone test, for overall survival (OS) and continuous complete remission (CCR). Chi-square analysis for comparisons of remission rates were. The impact of prognostic factors was studied using Cox regression model. p≤0.01, M=median, m=months. Cytogenetic abnormalities were seen in 62.1% of cases including: 32 (24,2%) complex abnormalities, 18 of them with >5 aberrations (vs 7,3% in <65 years p<0.001), twelve (9,1%) t(15;17), 7 trisomy 8, 3 trisomy 21, 3 trisomy 11, 3 del(7q), 2 t(8;21), 2 t(9;22), 2 del(5q), two 3q21q26 rearrangement, one inv h (16), one 11q rearrangement, one monosomy 7 and 8 with other abnormalities. One normal karyotype had FLT3 and NPM1 mutations. Karyotype was classified by SWOG and MRC classification. 21.2% showed trilineage myelodysplasia (TMDS) (vs 10% in <65 years p=0.003). 80 patients received intensive chemotherapy (11 with AML-M3 also received ATRA). Only 53.8%(43/80) achieved CR(vs 78 % in <65 years p<0.001) and this was lowest in complex karyotype (13.3%).The 5-year OS and CCR probability was: 6,2% (M=2.9 m) and 13,8% (M=1.5 m).The longest OS was for t(15;17) with 41,7% surviving at 5 years (M=10.0 m); normal karyotypes survive 2,28% and other abnormalities had very short survival (p<0.0001). Patients with complex karyotypes survive 0% at 17 months and all had relapsed at 5,3. Probability of relapse in t (15;17) was 51.31 % at 5 years (M 12,30), and this was higher in normal karyotype (93,4%), trisomy 8 (100%) and other abnormalities (100%) (p=0.0008). A longer OS was seen in patients with leucocytes ≤ 10×109/L (p=0.0006), subtype M3 (p=0.009)/t(15;17) (p<0.0001) who received ATRA (p=0.0001) and without TMDS (p=0.0043). FAB subtypes distinct of M3 (p=0.0046), age adapted chemotherapy treatment (p=0.0004) and complex karyotypes (p=0.0007) were unfavourable prognostic factors for CCR. The survival of cytogenetic groups according SWOG and MCR was significantly different (p=0.0005, p =0.0021 for OS; p<0.0001, p=0.0001 for CCR). Multivariate analysis showed that karyotype, TMDS and leucocytes are independent factor for OS. The higher risk of dead is for unfavourable (OR 2.94 p=0,008) and unknown (OR 2,52 p=0,03) cytogenetic SWOG groups. Only unfavourable SWOG karyotypes and chemotherapy without ATRA are independent factor for relapse risk. The elderly novo AML has a similar clinical-biological profile that the secondary AML, because of high frequency in undifferentiated subtypes, frequent TMDS, high percentage of complex abnormalities and poor CR, CCR and OS. This matter suggest that their aetiology is probably a lengthy exposure to environmental toxins. That's the reason because it's essential the cytogenetic study to decide induction chemotherapy or palliative support. Elderly patients with de novo AML which shown unfavourable SWOG abnormalities, failure to achieve CR, relapse promptly and have short survival. In this age group, today, only therapy designed to target specific molecular rearrangements has good prognostic.

Glycosylphosphatidylinositol (GPI) Protein-Negative Population of Leukemic Cells in Patients with De Novo Acute Leukemia.

Paroxysmal nocturnal hemoglobinuria (PNH) is considered to be an acquired stem cell disorder affecting all hematopoietic lineages, which lack GPI-anchored membrane proteins, such as CD59, because of abnormalities in the phosphatidylinositol glycan-class A (PIG-A) gene. Also, PNH is one disorder of the bone marrow failure syndromes, including aplastic anemia and myelodysplastic syndrome, which are considered as pre-leukemic states. In this study, to know some condition of pre-leukemic states in patients with de novo acute leukemia, we investigated the expression of CD59 in leukemic cells from 25 patients (female: male=8: 17; mean age, 57.8 ± 19.5 years) with de novo acute leukemia by single-color flow cytometric analysis. In addition, the PIG-A gene from CD59− leukemic cells, sorted by FACS Vantage, in 10 patients with acute leukemia was examined by sequence analysis. All the patients had no past history of PNH. Based on the French-American-British criteria, the diagnosis and subtypes of acute leukemia were determined. The number of patients with subtypes M1, M2, M3, M4, M5, and M7 was 1, 14, 2, 4, 2, and 2, respectively. Two of the patients were classified into acute myeloid leukemia with trilineage myelodysplasia from morphological findings in bone marrow. Chromosomal analyses presented abnormal karyotypes in 14 of 25 patients. Flow cytometric analyses showed that leukemic cells from 16 of 25 patients (64%) had negative populations of CD59 expression and the mean proportion of the populations was 63.3 ± 25.7%, suggesting the possibility that CD59− leukemic cells from patients with de novo acute leukemia might be derived from PNH clones. In fact, the PIG-A gene analyses showed that single (n=4) or multiple (n=6) PIG-A mutations in coding region were found in leukemic cells from 10 patients with CD59− leukemic cells and all of the clones with the PIG-A mutations were statistically minor. Then, various clinacal parameters, including peripheral blood, bone marrow blood, and laboratory findings and the results of chromosomal analyses were statistically compared between 2 groups of patients with (n=16) and without CD59− leukemic cells (n=9). The reticulocyte counts (mean ± standard deviation; 10.5 ± 13.0 x 104/μl) and proportions of bone marrow erythroblast (17.5 ± 13.9%) in patients with only CD59+ leukemic cells were significantly higher than those in patients with CD59− leukemic cells (2.5 ± 1.7 x 10 4/μl; p<0.05 and 5.6 ± 6.2%; p<0.01, respectively). The proportions of bone marrow blasts (69.3 ± 21.1%) in patients with CD59− leukemic cells were significantly higher than that those in patients with only CD59+ leukemic cells (45.5 ± 19.3%; p<0.02). In conclusion, our findings indicate that leukemic cells derived from PNH clones may be fairly common in de novo acute leukemia patients, suggesting that bone marrow failure as pre-leukemic states may have already occurred in localized bone marrow even in de novo acute leukemia.

Hepatosplenic 33 T-Cell Lymphoma with Myelodysplastic Syndrome

We describe a patient with hepatosplenic 33 T-cell lymphoma who showed pancytopenia and myelodysplasia. A 35-year-old man was admitted with fever, pancytopenia, and hepatosplenomegaly but with no lymphadenopathy. We also found trilineage myelodysplasia in the bone marrow on his first admission. The patient had high fever and anemia but no evidence of infection and was tentatively treated with prednisolone. This treatment resulted in a transient improvement of the cytopenia and a reduction of spleen size. However, 10 months after the first manifestation, progression of the splenomegaly and fever became apparent, and a splenectomy was performed. The pathologic findings for the spleen showed diffuse and disseminated infiltration of medium- to large-sized T-lymphocytes in the splenic red pulp. These cells were immunohistochemically positive for CD3, CD5, CD7, CD8, CD16, CD56,T-cell receptor 33 (TCR33),T-cell intracellular antigen 1, and granzyme B but were negative for CD4, CD30, CD57, and TCR33. These data suggested a diagnosis of hepatosplenic 33 T-cell lymphoma. A Southern blot analysis revealed gene rearrangement of the TCR 3-chain gene but not the immunoglobulin heavy chain gene in the spleen cells. An in situ hybridization analysis for the Epstein-Barr virus revealed negative results. The patient received 8 courses of combination chemotherapy and achieved a partial remission; however, the dysplastic features of the marrow cells persisted after the partial remission was obtained. Additional treatment with allogeneic bone marrow transplantation resulted in a transient complete remission; however, the patient relapsed 11 months later. Because he had experienced no lymphadenopathy and showed dysplastic features in the bone marrow, the diagnosis was highly dependent on the pathologic findings for the resected spleen.

Therapy‐related myelodysplastic syndrome with monosomy 5 after successful treatment of acute myeloid leukemia (M2)

We describe a patient who developed myelodysplastic syndrome over 2 years after achieving complete remission of acute myeloid leukemia (AML). The patient was treated in July 1998 with anthracycline, etoposide, and behenoyl cytarabine chemotherapy for AML (French-American-British classification, M2; World Health Organization classification, AML with maturation) and achieved complete remission. At presentation, no chromosomal abnormalities were detected. In December 2000, the patient's peripheral blood revealed pancytopenia, and his bone marrow was hypocellular with trilineage myelodysplasia and no blasts. Chromosomal analysis revealed complex karyotypic abnormalities, including monosomy 5. The patient was diagnosed with high-grade myelodysplastic syndrome (MDS)/refractory anemia with excess blasts (RAEB) subtype. The pancytopenia progressed rapidly, and he died 2 months after the diagnosis of MDS. Therapy-related MDS and AML (t-MDS/t-AML) developing after treatment for acute leukemia is unusual; the primary leukemia associated with most cases of t-MDS/t-AML is acute promyelocytic leukemia (APL). This unusual case suggests that AML excluding APL should be considered a primary hematologic malignancy for t-MDS/t-AML.

STEM CELL TRANSPLANTATION AS CONSOLIDATION THERAPY FOR CHILDREN IN FIRST-REMISSION AML

A large number of patients affected by acute myeloid leukemia (AML) achieve complete remission following induction chemotherapy based on high-dose aracytin and anthracyclines. However, a postremission consolidation treatment appears to be essential to maintain the remission status. Sixteen patients with newly diagnosed AML received induction chemotherapy according to the AIEOP LAM 92P/Mod protocol. All patients were HLA-typed, and if no donor was identified within the family, patients underwent autologous stem cell transplantation (autoSCT) with mafosfamide-purged bone marrow. Patients with very high-risk AML (cytogenetics with t(9;22), hyperleukocytosis (540 × 109/L), and AML-M7 with trilineage myelodysplasia) underwent unrelated donor transplantation. One patient relapsed before autoSCT. Eleven patients underwent autoSCT with purged bone marrow, 3 patients underwent unrelated donor transplantation (UD), and 1 patient underwent HLA-identical, matched familiar donor transplantation (MFD). All patients achieved complete remission following one course. No treatment-related deaths occurred during first-line treatment. The median interval between diagnosis and transplant was 175 days (129–277). Three patients relapsed following autoSCT; none relapsed after alloSCT. Taking stem cell transplantation as the starting point, overall survival was 93%, disease-free survival (according to the chosen treatment) was 80%, the relapse rate was 20%, and transplant-related mortality was 0%.

Therapy-related acute myeloid leukemia after single-agent treatment with fludarabine for chronic lymphocytic leukemia

A 70-year-old man with B-cell chronic lymphocytic leukemia (CLL) received single-agent treatment with the purine analogue fludarabine, which led to complete remission. After 8 years, he presented with pancytopenia. Marrow examination showed acute myeloid leukemia (AML) with trilineage myelodysplasia (MDS). Cytogenetic analysis showed an unbalanced der(1;7)(p10;q10) that resulted effectively in deletion 7q; confirming the diagnosis of therapy-related AML (t-AML). No residual CLL was present. Together with previous reports of secondary cancers after fludarabine treatment and the association of monosomy 7/7q- with another purine analogue azathioprine, results suggest that t-AML might develop after fludarabine therapy.

Overexpression of EVI1 in Translocation t(3;8)(q26;q24) in a Patient with Trilineage AML.

EVI1 is a transcription factor that is targeted for de-regulation in 10% of patients with acute myeloid leukemia (AML). Overexpression of EVI1 is associated with a particularly poor prognosis. Various karyotypic abnormalities involving chromosomal region 3q26 have been shown to inappropriately activate expression of EVI1, the most frequent alterations being inv(3)(q21q26)and t(3;3)(q21;q26). Rearrangements of 3q are frequently associated with trilineage myelodysplasia, especially dysmegakaryocytosis. So far, translocation t(3;8)(q26;q24) has been reported in one patient with MDS and two cases of AML without further molecular analysis. No other recurrent chromosome aberration with a breakpoint in 8q24 has been shown in AML. We report a case of a 58 year old male patient with a multilineage AML featuring a t(3;8)(q26;q24) as the sole chromosomal aberration in 80% of bone marrow cells analysed by conventional cytogenetics. The normocellular bone marrow aspirate showed 25–50% atypical blasts, dyserythropoiesis, dysplastic myelopoiesis and hyperactivated megakaryopoiesis with many micromegakaryocytes. Immunophenotyping of the blast population by flow cytometry confirmed the myeloid nature of the cells with CD13+, CD33+, CD64+, CD117+, HLA−DR+ phenotype and variable expression of CD14 and CD34. Persisting pancytopenia occurred after two cycles of chemotherapy and a relapse was evident 4 months later. By real time quantitative RT-PCR (RQ-PCR) we showed that EVI1 is highly overexpressed (>100:1) in this patients bone marrow cells as compared with an AML patient without 3q26 involvement. Fluorescence in situ hybridisation (FISH) is currently being performed to characterize the 8q24 and 3q26 breakpoints in more detail.The chromosomal translocation t(3;8)(q26;q24) leads to overexpression of EVI1 and, as in other aberrations involving 3q, shows a poor prognosis in AML.

Characteristics of De Novo Acute Leukemia Patients with Glycosylphosphatidylinositol (GPI) Protein-Negative Population of Leukemic Cells.

Paroxysmal nocturnal hemoglobinuria (PNH) is considered to be an acquired stem cell disorder affecting all hematopoietic lineages, which lack GPI-anchored membrane proteins, such as CD59, because of abnormalities in the phosphatidylinositol glycan-class A (PIG-A) gene. Also, PNH is one disorder of bone marrow failure syndromes, including aplastic anemia and myelodysplastic syndrome, which are considered as pre-leukemic states. In this study, to know some characteristics of patients with de novo acute leukemia, we investigated expression of CD59 in leukemic cells from 25 patients (female: male=8: 17; mean age ± standard deviation, 57.8 ± 19.5 years) with de novo acute leukemia by single-color flow cytometric analysis. In addition, the PIG-A gene from CD59− leukemic cells sorted by FACS Vantage in 3 patients with acute leukemia was examined by sequence analysis. All the patients had no past history of PNH. Based on the French-American-British criteria, the diagnosis and subtypes of acute leukemia were determined. The number of patients with subtypes M1, M2, M3, M4, M5, and M7 was 1, 14, 2, 4, 2, and 2, respectively. Two of the patients were classified into acute myeloid leukemia with trilineage myelodysplasia from morphological findings in bone marrow. Chromosomal analyses presented abnormal karyotypes in 14 of 25 patients. Flow cytometric analyses showed that leukemic cells from 16 of 25 patients (64%) had negative populations of CD59 expression and the proportion of the populations was 63.3 ± 25.7%, suggesting the possibility that CD59− leukemic cells from patients with de novo acute leukemia might be derived from PNH clones. In fact, the PIG-A gene analyses showed that monoclonal or oligoclonal PIG-A mutations in coding region were found in leukemic cells from 3 patients with CD59− leukemic cells and all of the clones with the PIG-A mutations were minor. Then, various clinical parameters, including rate of complete remission for remission-induction chemotherapy, peripheral blood, bone marrow blood, and laboratory findings, and results of chromosomal analyses were statistically compared between 2 groups of patients with (n=16) and without (n=9) CD59− leukemic cells. The reticulocyte counts (10.5 ± 13.0 x 104/μl) and proportions of bone marrow erythroblasts (17.5 ± 13.9%) in patients with only CD59+ leukemic cells were significantly higher than those (2.5 ± 1.7 x 104/μl, p<0.05; and 5.6 ± 6.2%, p<0.01, respectively) in patients with CD59− leukemic cells. The proportions of bone marrow blasts (69.3 ± 21.1%) in patients with CD59− leukemic cells were significantly higher than those (45.5 ± 19.3%, p<0.02) in patients with only CD59+ leukemic cells. In conclusion, our findings indicate that leukemic cells derived from PNH clones may be common in de novo acute leukemia patients, suggesting that bone marrow failure may have already occurred in localized bone marrow even in de novo acute leukemia.

Anaplastic large‐cell lymphoma which showed severe inflammatory status and myelodysplasia with increased VEGF and IL‐6 serum levels after long‐term immunosuppressive therapy

We report a patient with anaplastic large-cell lymphoma (ALCL) who has been given immunosuppressive therapy for Evans syndrome for 10 years. He was admitted with spike fever, intra-abdominal lymphadenopathy, and multiple liver masses. Examination of biopsy specimens obtained by para-aortic lymph nodes and liver masses resulted in a diagnosis of ALCL. Immunohistochemically, these cells were reactive to anti-CD30 antibody but were not of B- or T-lineage. Bone marrow aspiration demonstrated the invasion of giant neoplastic cells and trilineage myelodysplasia. Because the patient showed severe inflammatory symptoms, we examined serum levels of various cytokines. Pretreatment levels of IL-6 and VEGF in this patient were significantly elevated compared to those of normal controls. He was treated with combination chemotherapy (ABVD regimen), achieving complete remmesion. Myelodysplasia and serum IL-6 and VEGF also normalized after treatment. We assumed that ALCL resulted from long-term immunosuppressive therapy and that the up-regulation of IL-6 and VEGF played a role in pathogenesis of this type of lymphoma. Am. J. Hematol. 66:49–52, 2001. © 2001 Wiley-Liss, Inc.

PARVOVIRUS B19 INFECTION REMINISCENT OF MYELODYSPLASTIC SYNDROME IN THREE CHILDREN WITH CHRONIC HEMOLYTIC ANEMIA

The authors have seen transient pancytopenia with erythroid hypoplasia and striking trilineage myelodysplasia reminiscent of true myelodysplastic syndrome (MDS) in 3 children, 1 with thalassemia intermedia and the other 2 with previously undiagnosed hereditary spherocytosis. In these 3 children transient pancytopenia and myelodysplasia coincided with serological evidence of acute parvovirus B19 (PV-B19) infection, strongly suggesting their relevance. It is of interest that these 3 cases were encountered within a period of 6 months. This might be an incidental event, but it might also be concluded that acute PV-B19 infection associated transient pancytopenia with morphological appearance of MDS may occur more frequently than reported in the literature. So, PV-B19-associated nonclonal MDS should be considered in the differential diagnosis of trueclonal MDS.

Translocation (12;17)(q13;q23) in de Novo Acute Myeloid Leukemia with Trilineage Myelodysplasia

12q13 abnormalities have been reported to be associated with a variety of benign and malignant solid tumors. Recently, they have been shown to be a nonrandom karyotypic change in acute myeloid leukemia. We report a case of de novo acute myeloid leukemia with trilineage myelodysplasia showing t(12;17)(q13;q23) as the sole chromosomal abnormality. A review of the literature indicates that 12q13 translocation in acute myeloid leukemia is often associated with concomitant dysmyelopoietic changes. There is also evidence to suggest that 12q13 translocation occurs more frequently in acute myeloid leukemia with a prior history of mutagenic exposure or karyotypic indicators of secondary leukemia.

Acute myeloid leukemia in the elderly

The optimal management of acute myeloid leukemia in patients over 60 years-of-age remains a controversial issue. The complete remission rates after conventional induction chemotherapy progressively decreases after the age of 60. This is explained by host-related factors and by differences in the biology of leukemia. The incidence of adverse prognostic factors (trilineage myelodysplasia, unfavorable karyotype, mdrl-positive phenotype) is higher in elderly patients. Three strategies are currently offered to older adults with acute myeloid leukemia: intensive chemotherapy, palliative treatment and attenuated dose chemotherapy. Currently, complete remission rates achieved with conventional chemotherapy range from 40–65% according to inclusion criteria. In the past few years, two approaches have been tested in order to improve the results of induction chemotherapy: modifications of chemotherapy regimens with new intercalating agents (idarubicin, mitoxantrone) and the use of myeloid growth factors. Myeloid growth factors have been administered with two objectives: to reduce the duration of neutropenia and the toxic death rate when given after induction chemotherapy, and to prime leukemic blasts when given during chemotherapy. The results of published placebo-controlled studies are discussed. The issues of palliative treatment and of attenuated dose chemotherapy are also addressed in the review, with special emphasis on the role of oral idarubicin.