Quimioterapia intensiva asociada a imatinib en leucemia linfoblástica aguda del adulto, Philadelphia positivo. Experiencia en un hospital público / Intensive chemotherapy with tyrosine kinase inhibitors in philadelphia-positive acute lymphoblastic leukemia

Background: Before the advent of tyrosine kinase inhibitors (TKIs), patients with Philadelphia-positive Acute Lymphoblastic Leukemia (Ph+ALL) had a poor prognosis. The association of TKIs to intensive chemotherapy (CT) improved outcome. Aim: To evaluate results of an intensive CT protocol including TKI in a public hospital in Santiago, Chile. Material and Methods: All patients with Ph+ALL diagnosed between January 2010 and February 2019, and who met inclusion criteria for intensive CT, received the Ph+ALL national protocol in association with imatinib and were included in this analysis. Results: Thirty-five patients aged 15 to 59 years received treatment. Complete response (CR) was obtained in 97%. Measurable residual disease (MRD) was negative in 61% (19/31 evaluable cases) during follow-up, and 55% (16/29) were MRD (-) before three months. Relapse was observed in 13 cases. Three patients underwent allogeneic hematopoietic stem cell transplant (HSCT), two in CR1. The overall survival (OS) and event-free survival (EFS) at three years were 52 and 34%, respectively. In patients who achieved MRD negativity before three months, no statistically significant differences in OS (64 and 42% respectively, p = 0.15) or EFS (35 and 32% respectively, p = 0.37) were observed. Conclusions: The prognosis of Ph+ALL improved with the association of imatinib to intensive CT. MRD-negative status before three months in this series was not significantly associated with better outcomes. Our series suggests that the Ph+ALL national protocol associated to TKI is a therapeutic alternative with high CR and aceptable MRD (-) rates.

Aumento renal bilateral como manifestação de leucemia linfocítica aguda / Bilateral renal increase as a manifestation of acute lymphocytic leukemia

As leucemias são o tipo mais frequente de câncer em crianças e adolescentes. A leucemia linfocítica aguda é a forma mais comum de leucemia na infância. A doença surge normalmente entre dois e quatro anos de idade, sendo incomum antes de um ano de vida. As manifestações mais comuns incluem febre, fadiga, letargia, dor óssea e articular. Em 50% dos casos, há hepato e/ou esplenomegalia e linfonodomegalias. Este relato de caso fala sobre uma menina de nove meses que foi levada à emergência do hospital por distensão abdominal, fraqueza em membros inferiores e constipação duas semanas antes. Apresentava massas abdominais endurecidas em flancos, abaulamento em região fronto-temporal direita e linfonodomegalias cervicais. A primeira impressão foi de nefroblastoma bilateral (Tumor de Wilms). A ecografia abdominal e a tTC de abdome mostraram aumento de volume renal bilateral e descartaram nefroblastoma. Em setor de oncologia pediátrica, foi realizada imunofenotipagem compatível com leucemia/linfoma linfoblástico B. No líquor havia 400 células p/uL com 81% de blastos. A avaliação neurológica e a RNM de crânio e neuro-eixo descartaram alteração que justificasse a paresia de membros inferiores. No décimo dia de tratamento, os rins já haviam reduzido até o limite superior da normalidade. O abaulamento da face já havia desaparecido. A paciente apresentou anemia, neutropenia, plaquetopenia e hipoalbuminemia severas. Ao final da indução, apresentou sepse fúngica e bacteriana evoluindo para choque séptico e parada cardiorrespiratória não responsiva às manobras de reanimação. Não foi realizado medulograma no final da indução por piora do quadro clínico e posterior óbito (AU)

Leukemias are the most frequent type of cancer in children and adolescents. Acute lymphocytic leukemia is the most common form of childhood leukemia. The disease usually arises between two and four years of age, being uncommon before one year of life. The most common manifestations include fever, fatigue, lethargy, bone and joint pain. In 50% of cases, there is hepatomegaly and/or splenomegaly and lymph node enlargement. This case report tells of a nine-month old girl who was taken to the hospital emergency room due to abdominal distension, weakness in the lower limbs, and constipation for two weeks. She had abdominal masses that were hardened on the flanks, bulging in the right fronto-temporal region and cervical lymph node enlargements. The first impression was bilateral nephroblastoma (Wilms tumor). Abdominal ultrasound and abdominal CT showed bilateral renal volume increase and ruled out nephroblastoma. In the pediatric oncology sector, immunophenotyping compatible with lymphoblastic leukemia/lymphoma was performed. In the CSF there were 400 cells/L with 81% blasts. Neurological evaluation and MRI of the skull and neuro-axis ruled out alterations justifying lower limb paresis. By the tenth day of treatment, the kidneys had already reduced to the upper limit of normal. The bulging of the face was gone. The patient presented severe anemia, neutropenia, thrombocytopenia and hypoalbuminemia. At the end of the induction, she presented fungal and bacterial sepsis evolving to septic shock and cardiorespiratory arrest unresponsive to resuscitation maneuvers. No myelogram was performed at the end of the induction due to worsening of the clinical picture and subsequent death (AU)

CALLA negative precursor B lymphoblastic leukemia with MLL gene translocation and an unusual FISH signal pattern.

Rearrangements of the mixed lineage leukemia (MLL) gene at 11q23 commonly occur in infants with CALLA negative B lymphoblastic leukemia (B-ALL). Most often, these are detected by conventional karyotyping; however, fluorescent in-situ hybridization (FISH) with the help of a dual-color break-apart probe is used to identify cryptic translocations. When there is an MLL gene translocations the usual FISH signal pattern is 1 red-1 yellow fusion signal pattern We present a case of an infant with CALLA negative precursor B-ALL with a characteristic translocations t(4;11) (q21;q23),however,with an unusual MLL FISH signal pattern.

Erythroleukemia Relapsing as Precursor B-cell Lymphoblastic Leukemia / 대한진단검사의학회지

AML relapsing as ALL has rarely been reported. We describe the case of a 62-yr-old man who was diagnosed with erythroleukemia with a complex karyotype and achieved complete hematologic and cytogenetic remission after induction chemotherapy. However, 4 months after the initial diagnosis, he showed relapse with blasts showing a different morphology and immunophenotype and was diagnosed with precursor B-cell ALL. The relapsing precursor B-cell ALL presented with the same leukemic clones as the primary erythroleukemia. Cytogenetic analysis of his bone marrow (BM) at the time of the primary erythroleukemia showed complex karyotypic abnormalities, including monosomy 5 and monosomy 7. At relapse, his BM showed reemergence of these leukemic clones of complex karyotypic abnormalities with clonal switch. To our knowledge, this is the first case of a lineage switch from erythroleukemia to ALL.

A Case of Adult B Lymphoblastic Leukemia with ider(9)(q10)t(9;22)(q34;q11.2) and der(19)t(1;19)(q23;p13.3) / 대한진단검사의학회지

In B lymphoblastic leukemia/lymphoma (B-ALL/LBL), t(9;22)(q34;q11.2) and t(1;19)(q23;p13.3) are recurrent cytogenetic abnormalities. The concurrent occurrence of both abnormalities is very rare, and only 3 cases have been previously reported. Here, we report a case of adult B-ALL with ider(9)(q10)t(9;22)(q34;q11.2) and der(19)t(1;19)(q23;p13.3). A literature review revealed that ider(9) (q10)t(9;22) is a rare variant of t(9;22) with a deletion of the short arm of chromosome 9. Fifteen cases of ider(9)(q10)t(9;22) have been reported. This abnormality is specific to precursor B-lymphoid neoplasms, such as B-ALL or B-lymphoid blast phase of CML, and is associated with disease progression or short survival. The cytogenetic abnormality t(1;19) is also specific to B-ALL. In most instances of t(1;19), TCF3 is fused to PBX1; however, a few cases have identical translocations but no TCF3-PBX1 fusion, as was observed in our patient. We describe the first case of ider(9)(q10)t(9;22) in combination with TCF3-PBX1 negative t(1;19). The patient underwent imatinib therapy in addition to intensive chemotherapy, but failed to achieve remission.

Dificuldade diagnóstica em dois casos de neoplasia de células linfóides precursoras cutâneas primárias / Diagnostic pitfalls in two cases of primary cutaneous neoplasia of precursor lymphocytes

O linfoma linfoblástico (LLB) é uma neoplasia maligna de linfócitos precursores (B, T ou células NK). O comprometimento primário da pele é raro. Relatamos as características clínicas, anatomopatológicas e imunofenotípicas em dois pacientes com apresentação cutânea primária que, histologicamente, apresentavam infiltrado de células imaturas. A análise imunofenotípica foi realizada com amplo painel de anticorpos. A pesquisa de rearranjo no gene do receptor de células T (TCR-gama) pelo método de reação em cadeia da polimerase (PCR) resultou positiva em um caso, que era CD56 positivo, classificado como linfoma de células NK blásticas-símile. Este caso representa uma entidade distinta derivada de células precursoras num estágio precoce de uma via comum de diferenciação para células T e NK. O outro caso foi classificado como LLB-T com expressão aberrante de CD79a, o que poderia ser erroneamente interpretado. O diagnóstico correto depende da utilização de um amplo painel de anticorpos para caracterização imunofenotípica e avaliação molecular.

The lymphoblastic lymphoma (LBL) is a malignant neoplasm of precursor lymphocytes (B, T or NK-cells). The primary involvement of the skin is rare. We examined the clinical, anatomopathological and immunophenotypic features of two patients with primary cutaneous involvement. Histologically they showed an infiltrate of immature cells. The immunophenotypic analysis was performed with a comprehensive panel of antibodies. T-cell receptor rearrangement (TCR-gamma) was analyzed with polymerase chain reaction (PCR) and it was positive in one case, which was CD56 positive, classified as blastic NK-cell-like lymphoma. This case represents a distinct entity derived from precursor cells at an early stage of a common developmental pathway for T and NK cells. The other case was classified as T-cell lymphoblastic lymphoma with aberrant expression of CD79a, what could be a diagnostic pitfall. The accurate diagnosis depends on the use of a comprehensive panel of antibodies for immunophenotypic characterization and molecular analysis.

A Case of CD45-, CD19- Precursor B Cell Acute Lymphoblastic Leukemia with an Atypical Morphology / 대한진단검사의학회지

The differential diagnosis of acute lymphoblastic leukemia (ALL) from other small round blue cell tumors in children is very important for proper treatment, but sometimes difficult. CD45 is expressed on almost all-human leukocytes and not expressed on other small round blue cell tumors. Moreover, CD19 is expressed on all stages of B lineage cells and loss of this antigen is very rare in precursor B-cell ALL. We report a case of ALL with atypical morphology and immunophenotype. A 6-yr-old girl presented with fever and weight loss. Many abnormal cells with variable sized, high nuclearcytoplasmic ratio and distinct nucleoli were counted 23% in bone marrow. The results of immunophenotyping were negative for CD45, CD19, CD10, CD20, CD3, CD5, CD7, CD56/16, CD13, and CD33 and positive for CD22, TdT, and CD34. The immunohistochemical staining of bone marrow biopsies was positive for CD79a, CD10, TdT and CD99. The cytogenetic study showed normal karyotype but amplification of MLL (myeloid/lymphoid or mixed lineage leukemia) gene was suggestive in the fluorescent in situ hybridization. The patient received the standard chemotherapy for acute lymphoblastic leukemia and reached complete remission.

Leucemia pré-B: apresentaçäo de 4 casos / Pre-B-cell leukemia: report of 4 cases

Quarenta e cinco leucemias linfoblásticas agudas (LAL) foram testadas imunologicamente. Quatro com as características de LAL pré-B, isto é, a presença de cadeia intracitoplasmática detectas por imunofluorescência direta, sem imunoglobulina de membrana. Estes quatro casos exprimiam o antígeno de membrana HLA-DR, e um caso com o antígeno reconhecido pelo anticorpo monoclonal J-5 (CALLA). Estes quatro pacientes, dois adultos e duas crianças, apresentavam síndrome clínica e biológica de mau prognóstico com características tumoral e hiperleucocitose