Efficacy of CLAE Chemotherapy Regimen Followed by Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the efficacy and safety of CLAE intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed/refractory acute leukemia (R/R AL).@*METHODS@#CLAE regimen [cladribine 5 mg/(m2·d), d 1-5; cytarabine 1.5 g/(m2·d), d 1-5; etoposide 100 mg/(m2·d), d 3-5] followed by allo-HSCT was used to treat 3 R/R AL patients. The patients received CLAE chemotherapy in relapsed or refractory status and underwent bone marrow puncture to judge myelodysplastic state. After an interval of 3 to 5 days, followed by preconditioning regimen for allo-HSCT [fludarabine 30 mg/(m2·d), d -7 to d -3; busulfan 0.8 mg/kg q6h, d -6 to d -3 or d -5 to d -2. If the bone marrow hyperplasia was not active and the blasts were less than 10%, busulfan should be used for 3 days. If the bone marrow hyperplasia was active and the blasts were more than 10%, busulfan should be used for 4 days]. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were used for graft-versus-host disease (GVHD) prevention. After transplantation, the status of minimal residual disease (MRD) and bone marrow chimerism were regularly monitored in all 3 patients, and demethylation drugs or dasatinib were used to prevent recurrence 3 months after transplantation.@*RESULTS@#2 patients with t(11;19) translocation and relapse/refractory acute myeloid leukemia recurred within 6 months after induction of remission, and received intensive chemotherapy with CLAE regimen followed by haploidentical allo-HSCT and unrelated donor allo-HSCT, respectively. The two patients both relapsed 6 months after transplantation, then achieved complete remission by donor lymphocyte infusion, interferon, interleukin-2 and other methods, and disease-free survival was 2 years after transplantation. The other patient was chronic myelogenous leukemia who developed acute lymphoblastic leukemia during oral administration of tyrosine kinase inhibitor, accompanied by T315I and E255K mutations in ABL1 kinase region and additional chromosomal abnormalities. After morphological remission by induction chemotherapy, central nervous system leukemia was complicated. Intensive chemotherapy with CLAE regimen followed by sibling allo-HSCT was performed in the positive state of MRD. The patient relapsed 3 months after transplantation, and achieved remission after chimeric antigen receptor T-cell (CAR-T) therapy, however, he died 5 months after transplantation because of severe cytokine release syndrome (CRS) and GVHD.@*CONCLUSION@#CLAE regimen followed by allo-HSCT may be an effective salvage treatment option for R/R AL patients to prolong the overall survival.

A Retrospective Study on the Efficacy and Safety of Idarubicin Combined with High-Dose Cytarabine Consolidation in Patients with Acute Myeloid Leukemia over 60 Years of Age in First Remission / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of idarubicin combined with high-dose cytarabine as a post-remission therapy for elderly patients with acute myeloid leukemia (AML).@*METHODS@#From November 2017 to June 2021, 24 AML patients aged ≥60 years who were in complete remission for the first time were enrolled in consolidation chemotherapy with idarubicin (10 mg/m2 intravenously once for day 1) combined with high-dose cytarabine (1.5 g/m2 intravenously over 3 hours every 12 hours for day 1-3), and the efficacy and safety were observed.@*RESULTS@#Among the 24 patients, there were 12 males and 12 females, the median age was 65 (60-78) years old, and the median follow-up time was 23.3 (2-42.7) months. By the end of the follow-up, 15 patients relapsed and 11 patients died. The median disease-free survival (DFS) was 9 months and there were 3 cases of 2-year DFS. The median overall survival (OS) was 16.2 months, and there were 4 cases of 2-year OS. In terms of safety, 6 patients had grade 1-2 non-hematological adverse reactions, 12 patients had grade 3-4 hematological adverse reactions, and a total of 6 patients developed infection after consolidation chemotherapy. Multivariate analysis showed that two induction cycles and high-risk cytogenetic abnormalities were the adverse factors of DFS and OS in elderly patients with AML in this study.@*CONCLUSION@#For AML patients ≥60 years old in first complete remission, idarubicin combined with high-dose cytarabine as post-remission therapy has a better safety, but compared with other regimens does not improve the prognosis of elderly patients, which needs further exploration.

Avaliação do método da imunofenotipagem por citometria de fluxo no diagnóstico das doenças displásicas (SMD, LMA-relacionada à mielodisplasia, LMMC e LMMJ) em adultos e crianças / Evaluation of the method of immunophenotyping by flow cytometry in the diagnosis of dysplastic disease (MDS, AML-related to myelodysplasia,CMML and JMML) in adults and children

As síndromes mielodisplásicas (SMD) se caracterizam por terem uma hematopoese displásica, citopenias e pelo risco de progressão para leucemia mielóide aguda. O diagnóstico baseia-se na clínica e nos achados citomorfológicos da medula óssea (MO) e citogenéticos. Na fase inicial ou quando a MO é hipocelular o diagnóstico é difícil e a citogenética frequentemente é normal. A imunofenotipagem (IMF) tem sido cada vez mais utilizada nos casos de SMD em adultos e pouco explorada na SMD pediátrica. Os nossos objetivos foram: estudar os casos de SMD e doenças correlatas (LMA relacioanda à SMD: LMA-rMD; leucemia mielomonocítica crônica: LMMC e leucemia mielomonocítica juvenil: LMMJ) em adultos e crianças, associando os dados clínicos e laboratoriais aos obtidos pela IMF, que utilizou um painel de anticorpos monoclonais para as várias linhagens medulares. No período compreendido entre 2000 e 2010 foram estudados 87 pacientes (64 adultos e 23 crianças) oriundos do HUPE/UERJ e IPPMG/UFRJ e 46 controles (23 adultos e 20 crianças). Todos os doentes realizaram mielograma, biópsia óssea, citogenética, citoquímica e estudo imunofenotípico. Segundo os critérios da OMS 50 adultos foram classificados como SMD, 11 como LMA-rMD e 3 LMMC. Entre as crianças 18 eram SMD, 2 LMA e 3 LMMJ. Os pacientes adultos com SMD foram divididos em alto risco (n=9; AREB-1 e AREB-2) e baixo risco (n=41; CRDU, CRDM, CRDM-SA, SMD-N e SMD-5q). As crianças com SMD em CR (n=16) e AREB (n=2). Anormalidades clonais recorrentes foram encontradas em 22 pacientes adultos e em 7 crianças. Na análise de IMF foi utilizada a metodologia da curva ROC para a determinação dos valores de ponto de corte a fim de identificar os resultados anormais dos anticorpos monoclonais nos pacientes e nos controles, permitindo determinar a sensibilidade e especificidade desses em cada linhagem. A IMF foi adequada para a análise em todos os pacientes e 3 ou mais anormalidades foram encontradas. A associação da IMF...

Myelodysplastic syndrome (MDS) is characterized by having a dysplastic hematopoiesis, cytopenias and risk of progression to acute myeloid leukemia. The diagnosis is based on clinical and cytomorphologic findings in bone marrow (BM) and cytogenetics. In the initial phase of when the BM is hypocellular, diagnosis is difficult and often with normal karyotype. The flow cytometry immunophenotyping (FCI) analysis has been broadly used in adult MDS cases but is rarely in pediatric MDS. The objectives of this work were: to study MDS cases and correlated diseases (AML with myelodysplasia-related changes; chronic myelomonocytic leukemia - CMML and juvenite myelomonocytic leukemia - JMML) and to correlate laboratorial data to FCI using a panel of monoclonal antibodies for the various marrow lineages in both adult and children. In the period between 2000 and 2010, 87 patients were studied (64 adults and 23 children) coming from HUPE/UERJ and IPPMG/UFRJ and 46 controls (26 adults and 20 children). All patients were submitted to myelogram, bone marrow biopsy, cytogenetic, cytochemistry and immunophenotypic study. According to WHO criteria 50 adults were classified MDS, 12 AML and 3 CMML. Among the children there were 18 MDS, 2 AML, and 3 JMML. MDS adult patients were subdivided into high risk (n=9; RAEB-1 and RAEB-2) and low risk (n=41; RCUD, RCMD-RS, MDS-U and MDS-5q). MDS children were classified as RCC (n=16) and RAEB (n=2). Clonal abnormalities were found in 22 (35%) adult patients and 7 (30%) children. In the analysis of FCI methodology ROC curve was used for determination of cut off abnormalities at monoclonal antibodies in patients and controls which allowed to estimate the sensitivity and specificity of each strain. The FCI was suitable for analysis in all patients and 3 or more abnormalities were found. The association of the FCI increased the sensitivity of morphological analysis in the erythroid lineage from 70 to 97% in adults and from 59 to 86% in children...

Severe congenital neutropenia [Kostmann Syndrome]

Severe congenital neutropenia [SCN], Kostmann syndrome is a heterogenous disorder of myelopoiesis characterized by severe chronic neutropenia, absolute neutrophil count [ANC] persistently below 0.50 x 109/L, with maturation airest of neutrophil precursors in the bone marrow; and associated with serious recurrent b…eteriiinfections from early infancy. Sepsis mortality is reduced by an advent of granulocyte colony stimulating factor [G-CSF] therapy. More than 90% of patients respond to G-CSF therapy. However, hematopoietic stem cell transplantation has shown promise in the treatment of non-responders. About 60-80% of SCN cases are associated with constitutive mutations in one copy of the gene encoding neutrophil elastase ELA2. Myelodysplastic syndrome and acute myeloid leukemia [MDS/AML] have been reported. The hazard of MDS/AML increases significantly overtime. Approximately 10% of patients with severe congenital neutropenia develop AML. This is not thought to be the direct result of G-CSF therapy but related to the underlying disease itself

A Case Report of the Second de Novo Acute Myeloid Leukemia (AML) Following Allogeneic Stem Cell Transplantation in a Patient with the First AML

Secondary leukemia occurring after hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) is rare. Secondary AML usually follows autologous and not allogeneic transplants. When a new leukemia develops in a patient successfully treated with an allogeneic HSCT, the possibility of a de novo or secondary leukemia from either the donor or recipient should be considered. We present a case initially diagnosed as de novo AML without a cytogenetic abnormality. The patient was successfully treated with an HLA-matched sibling allogeneic HSCT. However, more than six years later, AML developed again and was associated with new complex cytogenetic abnormalities. After a second HSCT, the patient has been followed without serious complications. Considering the allogeneic setting, the newly developed cytogenetic abnormalities, a relatively long latent period, and the good clinical course after the second allogeneic HSCT, this case might represent a second de novo AML following successful treatment of the first AML.

Granulocytic sarcoma.

We present two cases where GS was sole presentations, months before the diagnosis of AML.

Granulocytic sarcoma.

Granulocytic sarcoma (GS) is an extramedullary tumor mostly associated with acute or chronic myelogenous leukemia (AML). GS can virtually involve any structure in body. Rarely the tumor may be seen before the diagnosis of underlying hematological malignancies. We present two cases where GS was sole presentations, months before the diagnosis of AML.

A Case of Treatment-Related Myelodysplastic syndrome and Acute Myelogenous Leukemia Following High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Non-Hodgkin's Lymphoma

Treatment-related myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (t-AML) are now well established as complications of cytotoxic chemotherapy. We experienced a 28-yr-old female patient who developed t-MDS/t-AML with characteristic chromosomal abnormalities including 11q23 chromosomal rearrangement following high-dose chemotherapy with autologous stem cell transplantation (ASCT) for non-Hodgkin's lymphoma. The patient was admitted with bulky abdominal masses of B cell lineage non-Hodgkin's lymphoma. After 2 cycles of systemic chemotherapy of the Vanderbilt regimen, the patient underwent ASCT with high dose chemotherapy of the BEAC regimen. She also received radiation of 48 Gy for the residual periportal lymphadenopathy. The initial cytogenetic analysis of the infused mononuclear cells revealed a normal karyotype. Twenty two months after the ASCT, pancytopenia was noted and her bone marrow aspirate showed dysplastic hemopoiesis with myeloblasts up to 12% of nonerythroid nucleated cells. The patient was diagnosed as t-MDS (refractory anemia with an excess of blasts). Cytogenetic analysis showed complex chromosomal abnormalities including 11q23 rearrangement, which is frequently found in topoisomerase II inhibitor-related hematologic malignancies. Four months later, it was noted that the t-MDS had evolved into an overt t-AML. Cytogenetic analysis showed an evolving pattern with more complex abnormalities. The patient was treated with combination che-motherapy, but her leukemic cells were resistant to the therapy.

Four cases of therapy-related leukemia

Combination chemotherapy and radiation therapy have contributed to the successful treatment of various cancer patients. But the development of second malignancies is an inevitable complication of long-term cytotoxic treatment. The most serious and frequent of such complications is acute myelogenous leukemia (AML). Therapy-related leukemia is generally fatal. Since the number of patients exposed to chemotherapy is increasing each year, the clinical significance of this entity cannot be underestimated. There have been many investigations of therapy-related leukemia, but in Korea published reports are rare. We describe four such cases, involving one older female with lung cancer and three children with acute lymphoblastic leukemia (ALL) and malignant lymphoma. Alkylating agents were used for chemotherapy, and in one case, topoisomerase II inhibitor. Irrespective of the causative agents, the latency periods were relatively short, and despite induction chemotherapy in two, all survived for only a few months. During the follow-up of patients treated for primary malignancies, the possibility of therapy-related leukemia should always be borne in mind.

Myelodysplastic syndrome that progressed to acute myelomonocytic leukemia with eosinophilia showing peculiar chromosomal abnormality: a case report

Myelodysplastic syndrome is a closely related group of acquired bone marrow disorders characterized by ineffective and dysplastic hematopoiesis. These clonal disorders frequently progress to acute leukemia. Acute myelomonocytic leukemia with eosinophilia is characterized by an increase in abnormal eosinophils in the bone marrow, relatively good clinical course and inv (16) chromosomal abnormality. We experienced one case of refractory anemia with excess blasts which progressed to refractory anemia with excess blasts in transformation and finally to acute myelomonocytic leukemia with eosinophilia showing peculiar chromosomal abnormalities of der (1;7).

Pre leukemic granulocytic sarcoma of vagina. A case report with review of literature.

Granulocytic sarcoma is an extramedullary tumor of malignant granulocytic progenitor cells, that may precede the onset of acute myeloid leukemia or appear during the leukemic manifestation or blastic crisis of chronic myeloproliferative disorders. We describe a case of granulocytic sarcoma of vagina in a 27 year old woman treated with local radiotherapy. After seven months of follow up she developed acute myeloid leukemia. The case has been presented in view of its rarity and discussed in light of the available literature.

Efficacy of low-dose cytarabine therapy in myelodysplastic syndromes.

The efficacy of low-dose cytarabine given as 10 mg sub-cutaneously 12 hourly for 2 weeks and repeated at 2 to 3 weekly intervals was evaluated prospectively in 15 consecutive patients of myelodysplastic syndrome over a 3 year period. Response to therapy was assessed clinically and by haematological parameters including bone marrow examination. No patient achieved complete remission. Three patients responded partially. Four patients transformed into acute myelogenous leukaemia. Overall, the results of therapy were disappointing as all the 15 patients died within 6 months of diagnosis.

Leucemia mielóide aguda após tratamento da doença de Hodgkin / Acute mycloid leukemia after treatment of the Hodgkin's disease

O desenvolimento de leucemias agudas, principalmente a leucemia mielóide aguda constitui-se em uma complicaçäo grave em pacientes tratados com rádio e/ou quimioterapia para doença de Hodgkin e tem aumentado acentuadamente nos ultímos 15 anos. Säo descritos dois casos de leucemia mielóide aguda após rádio e quimioterapia para doença de Hodgkin que ocorreram em uma populaçäo de 87 pacientes tratados. Foram realizadas autópsias completas em ambos. Os pacientes tinham idade inferior a 30 anos, receberam terapêutica combinada por um período prolongado (mais de 12 meses) com intervalo entre o diagnóstico da doença de Hodgkin e o aparecimento da leucemia mielóide aguda maior que 44 meses e sobrevida menor que 12 meses. Näo se observou doença de Hodgkin residual nos dois casos

A case of pre-leukaemia masquerading as haemolytic anaemia due to multi-enzymopathy of the red cell.

A 19 year old woman presented as a case of haemolytic anaemia due to multi-enzyme deficiency of the erythrocyte. After a transient improvement with folic acid therapy, she developed acute myeloblastic leukaemia. This is the second reported case of a myelodysplastic syndrome presenting with a haemolytic picture and subsequently developing an acute myeloblastic leukaemia.