Impact of Aberrant Antigens in the Outcome of Patients with Acute Leukemia at a Referral Institution in Mexico City.

BACKGROUND: Patients with acute leukemia can express aberrant markers, defined as antigens that are normally restricted to a different lineage. The reported significance and frequency of these markers is inconclusive. We assessed the frequency and impact of aberrant markers in patients with acute leukemia in a referral institution in Mexico City. METHODS: We included 433 patients, diagnosed and treated between 2005 and 2015 in our institution. RESULTS: Aberrant markers were expressed in 128 patients (29.6%); CD13 and CD33 were the most frequent aberrant markers in patients with acute lymphoblastic leukemia, while CD7 and CD19 were the most frequent in patients with acute myeloid leukemia. In the univariate analysis, the group with aberrant markers had a lower disease-free survival when compared with the aberrant-free group (8 vs. 13 months) (p = 0.03). Aberrant expression of CD10, CD20, and CD33 correlated with a worse outcome in a statistically significant manner. In the multivariate analysis, male gender, lymphoid lineage, secondary leukemia, high risk at diagnosis, and the presence of aberrant markers had a significantly negative impact on disease-free survival. CONCLUSION: The use of more aggressive treatment strategies could be considered in patients with acute leukemia and an aberrant expression of CD10, CD20, and CD33.

ACUTE LEUKEMIAS IMMUNOPHENOTYPES AT AGAKHAN UNIVERSITY HOSPITAL, NAIROBI.

OBJECTIVE: The aim was to determine relative frequencies of acute leukemia immunophenotypes using commonly expressed markers and to describe the clinicopathological characteristics. Design: This was a prospective cross-sectional study. SETTING: The study was based at Aga khan clinical laboratory department. SUBJECTS: One hundred and thirty two (132) consecutive blood and bone marrow specimens from patients suspected to have acute leukemia were analysed for cytomorphological characteristics and immunophenotyping. The clinical-pathological characteristics were also recorded. Immunological category was assigned using the EGIL criteria. RESULTS: There were 88 AML and 42 ALL patients analysed for immunophenotypes. Only tw cases of biphenotypic leukemia were found. The commonest overall AML morphological sub-type was AML-M2, 26 (29.5%). Majority of ALL cases were B-cell immunological sub-type (96.6%). Early pre-B phenotype constituted 62.07% and Common B-cell ALL 37.93%. There were only 4 cases of T-cell ALL. Majority of patients presented with anaemia with a median hemoglobin of 7.5g/dl (range 2-15g/dl). The median platelet count was 55 (range 4-462 x 10(9)/L). CONCLUSION: Immunophenotyping of acute leukemia is beneficial in accurate diagnosis of patients with these malignancies in this setup. T-cell ALL, AML-M6 and M7 are less frequent than what has been reported in most studies in Africa.

A case report of lineage switch from T-cell acute leukemia to B-cell acute leukemia.

RATIONALE: ALL is the most common form of leukemia (75% to 80%), it is characterized by clonal expansion of the lymphoid blasts in bone marrow, blood, and other tissues, which can be divided into T lineage and B lineage. Although relapse of acute leukemia is common, a change of immunophenotype at relapse only occurs rarely. Some of these cases have been labeled "lineage switch". PATIENT CONCERNS: A 31-year-old man had multiple lymph nodes in the neck, and the lymph nodes on the right side adhered to the surrounding tissues. His lymphocytes ratio in blood was up to 86.3%. Flow cytometry of the bone marrow aspirate showed positive results for CD2, CD5, CD7, cCD3, TDT, CD4, CD8, and CD10, negative results for CD34, CD117, CD33, HLA-DR, CD19, and CD20. Twenty six months later, the patient felt pain in the neck and shoulder after touching. His lymphocytes of blood were 109.9×109 /L. 43 fusion genes and positive BCR/ABL was detected. Flow cytometry of the bone marrow aspirate showed pro B lymphocytes accounted for 85.54%, and positive expression of CD38, CD10, CD34, CD33, TDT, CD9, and HLA-DR. Moreover, the RT-PCR data showed the patient expressed high level of T cell and B cell development transcription factors. DIAGNOSES: Upon examination, the patient was initially diagnosed with T-lineage pro cell ALL. BM morphologic analysis presented complete remission (CR) after systemic chemotherapy. Twenty six months later, we discovered the patient was diagnosed with B-lineage acute lymphocytic leukemia. INTERVENTIONS: Systemic chemotherapy is first given when a patient was diagnosed with T-cell acute lymphoblastic leukemia. After the patient happened linage switch, we adjusted the treatment plan, and the patient was complete remission after 1 course of treatment. OUTCOMES: Our case provides information of lineage switch from T-ALL to B-ALL in this report, which is never seen in our knowledge. LESSONS: This lineage switch from T-ALL to B-ALL is never reported beforemoreover, the RT-PCR data showed the patient expressed high level of T cell and B cell development transcription factors. Its early recognition can let doctor provides appropriate therapy to patient.

Clinico-hematological profile in biphenotypic acute leukemia.

BACKGROUND: We present a clinico-hematological profile and treatment outcome of Biphenotypic Acute Leukemia (BAL). AIM: Study incidence and subtypes of BAL, correlate with age, morphology, and cytogenetic findings and correlate the clinico-hematological data with the treatment response. St Jude's and the EGIL's criteria have been compared for their diagnostic and clinical relevance. MATERIAL AND METHODS: Diagnosis was based on WHO classification, including clinical details, morphology, cytochemistry, immunophenotyping, and molecular genetics. We included those cases, which fulfilled the European Group for the Immunological Characterization of Acute Leukemia's (EGIL's) scoring system criteria for the diagnosis of BAL, as per recommendation of the WHO classification. RESULTS: There were 32 patients diagnosed with BAL, based on EGIL's criteria. Incidence of BAL was 1.2%. B-Myeloid (14 cases) followed by T-Myeloid BAL (13 cases) were the commonest subtypes. Polymorphous population of blasts (16 cases) was commonly associated with T-Myeloid BAL (10 cases). BCR ABL fusion positivity was a common cytogenetic abnormality (seven cases). Fifteen patients received chemotherapy; eight achieved complete remission (CR) at the end of the induction period. CONCLUSIONS: Pediatric BAL and T-B lymphoid BAL have a better prognosis. A comprehensive panel of reagents is required, including cytoplasmic markers; to diagnose BAL. St Jude's criteria is a simple, easy, and cost-effective method to diagnose BAL. The outcome-related prognostic factors include age, HLA-DR, CD34 negativity, and subtype of BAL. BCR-ABL expression is an important prognostic factor, as these cases will be labeled as Chronic myeloid leukemia (CML) in blast crisis with biphenotypic expression and treated accordingly.

Mixed-phenotype acute leukemia characteristics: first report from Iran.

Mixed-phenotype acute leukemia (MPAL) is the infrequent type of acute leukemia characterized by immunophenotypic and/or cytochemical features of both lineages, but the diagnosis of this disease still is a challenge. In this study, we analyzed immunophenotyping, cytochemistry and frequency of MPAL patients to better diagnosis of MPAL characteristics according to WHO 2016 criteria for the first time in Iran. In this retrospective study, 27 patients were diagnosed as MPAL based on WHO 2016 criteria during 2014-2017. Flow cytometric immunophenotyping was performed on PB and BM samples evaluation of different CD marker expressions in MPAL subsets. RT-PCR was performed for the analyses of BCR/ABL1 fusion in MPAL subsets. Among 27 cases, (70.4%) 19 cases were B + My, (22.22%) 6 cases were T + My, and 2 cases (7.40%) were B + T + My. CD34, CD19, HLA-DR, TdT, CD22, iMPO were positive in majority of B + My cases. CD45, iMPO, iCD3, CD7, CD2 and CD5 were positive in majority of T + My cases. HLA-DR, TdT, CD10, CD22, iCD79a, iMPO, CD45, iCD3, CD7, CD3, CD2, CD5 were positive in majority of B + T + My cases. BCR/ABL1 fusion was positive for 3 cases (11.1%) of p190 fusion and 2 cases (7.4%) of p210 fusion in B + My cases. WHO 2016 criteria are the current standard for diagnosing MPAL. Also, evaluation of TdT, CD2, CD5, CD7 expressions by flow cytometry in EGIL criteria is useful for the better diagnosis of MPAL subsets. In addition, evaluation of BCR/ABL1 and MLL rearrangements in patients should be part of standard work-up in MPAL.

Facilitation of functional compartmentalization of bone marrow cells in leukemic mice by biological response modifiers: an immunotherapeutic approach.

Biological Response Modifiers (BRMs) including interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and sheep erythrocytes (SRBC) protected N,N'-ethylnitrosourea (ENU) induced leukaemic mice. Two cell types from the bone marrow were isolated in density specific gradient representing two distinct compartments, the low density cells being more CD34 positive than the high density group. Investigations with the functional efficacy of such compartments revealed significant improvement of cytotoxic efficacy and phagocytic burst at the high density compartment (HDC) level. The high density compartment was found to be more responsive towards the BRMs compared to the cells of the low density compartment (LDC). It was suggested that use of BRMs in vivo can stimulate a potent functional progenitor compartmentalization in normal as well as leukaemic mice. These observations are expected to help a logistic approach towards combined BRM therapy at the clinical level.

Hand mirror variant of adult acute lymphoblastic leukemia. Evidence for a mixed leukemia.

Blast cells from a female patient with acute lymphoblastic leukemia-hand mirror variant were examined using various techniques, including light and ultrastructural morphologic examination, cytochemical analysis, surface antigen characterization, cytogenetic analysis, and gene rearrangement studies. The blast cells were found to be pre-B cells (CD19+ and Tdt+) that also expressed the myeloid antigens CD13 and CD33 and demonstrated a heavy chain immunoglobulin gene rearrangement. Cytogenetic studies revealed a t(11;19) translocation previously described in biphenotypic leukemias. A subset of acute lymphoblastic leukemia-hand mirror cells has been previously defined and includes predominately female patients with an indolent course. The authors' findings place this case, a mixed leukemia, within that subgroup. The possibility of mixed lineage should be considered in future cases of hand mirror variants of adult acute lymphoblastic leukemia. Furthermore, hand mirror morphologic features in any case of acute leukemia should alert the hematopathologist/hematologist to the possibility of mixed lineage.

[Hypoplastic mixed lineage leukemia successfully treated with low-dose cytosine arabinoside].

A 54-year-old male was admitted because of dyspnea on exercise. His peripheral blood revealed pancytopenia with severely hypoplastic bone marrow. Bone marrow aspiration showed a marked hypocellular marrow with 62.4% of blast cells. Cytochemical studies showed that peroxidase activity, alpha-nephtyl buthylate esterase activity and PAS reaction were negative, and that only ASD-chroloacetate esterase activity was positive. Surface marker analysis of blast cells showed positive result for CD5, 7, 33 and 34 antigens. The T-cell receptor beta gene was rearranged, but the immunoglobulin H chain gene showed a germ line configuration. Terminal Deoxynucleotydyl Transferase (TdT) was positive, but cellular surface and cytoplasmic immunoglobulin were not recognized. A diagnosis of hypoplastic mixed lineage leukemia was made and treated with low dose cytosine arabinoside, he resulted in complete remission. The relation between hypoplastic leukemia, AML-M0 and mixed lineage leukemia was also discussed.

[Acute mixed-cell human leukemia]. / Ostrye smeshanno-lineinye leikozy cheloveka.

The incidence rate of acute mixed-lineal leukemias, distinguished in a group of patients with acute non-lymphoblastic leukemia, in children and adults was about the same: CALLA 10-20%, T-cell antigens 15-22%, Thy-1 15-17%. The incidence rate of acute lymphoblastic leukemia with myeloid (17-21%) and erythroid (12-13%) antigens did not significantly differ in children and adults. Distinguishing features have been proposed for actual acute mixed-lineal leukemias having markers of mature stages of varying cell line differentiation from cryptic lineal-different-marker leukemias of bi- or polypotent precursor-cell origin.

Telemedicina no diagnóstico de doença linfoproliferativa num contexto de recursos limitados / Telemedicine in the diagnosis of lymphoproliferative disease in a context of limited resources

Os autores reportam um caso de Leucemia Linfoblástica Aguda - L1 da classificação Francesa ­ Americana ­ Britânica, numa criança moçambicana cujo diagnóstico específico foi confirmado através de consulta por via electrónica,realizada por um hospital rural em Moçambique e por um oncologista pediátrico num outro continente. A criança de 7 anos foi admitida ao hospital com um quadro grave de anemia, descompensação cardiorrespiratória secundária, febre, diarreia, linfadenopatias cervicais, hepatoesplenomegalia e leucócitemia de 120 x 103/mm3 (84.4% linfócitos). Apesar de o Hospital Rural em Moçambique dispor de recursos limitados, foi feito um diagnóstico definitivo e célere graças a troca de imagens do esfregaço de sangue periférico do paciente, sistematicamente gravadas com recurso a uma câmara fotográfica. As consultas à distância utilizando meios electrónicos permitiram para além do diagnóstico, a formação em serviço, do pessoal local através das orientações sobre condutas essenciais para correcta estabilização clínica do paciente. Este caso sugere a telemedicina como um mecanismo potencial de apoio dos hospitais especializados aos hospitais rurais, ajudando jovens profissionais no manejo de casos complexos. A sua aplicação deve ser estudada para orientar o seu uso correcto, informado e extensivo.

Thisis a report of a case of acute lymphoblastic leukemia - L1 French-American-British classification, in a Mozambican child, whose specific diagnosis was possible and confirmed through electronic consultation by a pediatric oncologist from another continent. The 7 year old child was admitted to hospital with severe anemia, secondary cardiac decompensation, fever, diarrhea, cervical lymphadenopathy, hepatosplenomegaly and white blood cells of 120 x 103/mm3 (84.4% lymphocytes). Despite the fact that rural hospitals in Mozambique have extremely limited resources, a specific diagnosis was made through exchange of systematically recorded pictures of patient's peripheral blood smears. The consultation by distance also allowed in-service training of local staff by sharing guidelines on essential conducts for proper clinical stabilization of the patient. This case suggests a potential means to deliver support from specialized hospitals to rural hospitals, helping young professionals in management of complex cases. Its application should be studied to guide proper, informed and possibly an extensive use.

Mastocitosis neoplásica en la evolución de una leucemia aguda de mal pronóstico / Neoplastic mastocytosis evolving from a poor prognosis acute myeloid leukemia

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Mixed-lineage leukemia revisited: acute lymphocytic leukemia with myeloperoxidase-positive blasts by electron microscopy.

Seven adult patients with untreated acute lymphocytic leukemia (ALL) who manifested 5% to 40% myeloperoxidase (MPO)-positive blasts by electron microscopy (EM) are reported. Six patients had an L2 morphology, and one had an L1 morphology by the French-American-British (FAB) classification. The immunophenotype was T cell in four patients. Molecular analysis showed rearrangement of the immunoglobulin JH in four patients, three of them also having rearrangement of the T-cell receptor beta or gamma. Induction chemotherapy with vincristine-doxorubicin-dexamethasone (VAD) produced a complete remission in five of six patients (83%). Our findings suggest the existence of a previously undescribed subtype of mixed-lineage leukemia, which by morphology and immunophenotype often appears as T-cell ALL but exhibits MPO-positive blasts by EM.