Clinical characteristics and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia arising from malignant tumors / 中华血液学杂志

Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.

Hematopoyesis Clonal de Potencial Indeterminado (HCPI): más allá de un modelo de campo de cancerización / Clonal hematopoiesis of indeterminate potential (CHIP): Beyond a model of field cancerization

Resumen La Hematopoyesis Clonal de Potencial Indeterminado (HCPI), más conocida como CHIP por sus siglas en inglés, se define como la expansión clonal de Células Madre Hematopoyéticas (CMHs) que albergan una o más mutaciones somáticas (en la mayoría de los casos una sola mutación) sin un cáncer hematológico subyacente ni evidencia morfológica definitiva de displasia, con una frecuencia alélica mayor al 2%. Los individuos con HCPI progresan a malignidad a una tasa de cerca del 0.5% a 1% por año, convirtiéndose así en un modelo de campo de cancerización. Sin embargo, sus implicaciones van más allá debido a que se ha encontrado asociación con enfermedades inflamatorias crónicas, como enfermedad cardiovascular ateroesclerótica, diabetes y enfermedades autoinmunes. Además, es considerado un factor predictivo en pacientes con cáncer hematolológico y no hematológico que reciben quimioterapia y radioterapia.

Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is the expansion of hematopoietic stem cells harboring one or more somatic mutations. These patients do not have underlying hematologic neoplasia, myelodysplasia, or dysplasia, but can progress to a malignant state at a rate of 0.5 to 1% per year. CHIP could be used as a model of field cancerization, since it has been associated with chronic inflammatory diseases, arteriosclerosis, diabetes, and autoimmune conditions. CHIP is also considered a predictive factor in hematological and non-hematological cancer patients receiving chemotherapy and radiotherapy.

Late-Onset Hematological Toxicity (LOHT) in Patients with B-Cell Lymphomas: A Survey in 758 Cases

ABSTRACT Background: The increasing survival of patients with non-Hodgkin lymphoma has allowed the diagnosis of long-term complications, including late-onset hematological toxicity (LOHT), transitory cytopenias, or therapy-related myeloid neoplasm (t-MDS/t-AML). Objective: The objective of the study was to determine the frequency and clinical evolution of LOHT in patients with lymphoproliferative malignancies. Materials and Methods: Two cohorts of patients B-cell lymphomas were reviewed. Patients who achieved full hematologic recovery at the end of treatment, and thereafter developed any degree of cytopenia were included in the study. Clinical and biochemical parameters were compared between patients with and without cytopenias with X2 test. Bi- and multivariate analyses were performed to evaluate factors associated with the development of late-onset cytopenias. Results: Of 758 patients enrolled, 19 developed cytopenias (2.5%). Transitory cytopenia was documented in 6 cases, 3 developed ICUS, 8 t-MDS, and 2 t-AML. In patients with FL, only hemoglobin < 12 g/dL (p = 0.032) and >6 nodal areas (p = 0.037) at diagnosis were factors statistically significant for the development of cytopenia. During cytopenias, 55% of patients died. Conclusions: LOHT constitutes a cause of morbidity and mortality in 2.5% of lymphoma patients treated with different therapy regimens.

Cancer therapy-related cardiovascular dysfunction and coronary microvascular dysfunction: Research progress / 第二军医大学学报

The risk of cardiovascular diseases is significantly increased in cancer patients receiving chemotherapy or radiotherapy. Recent evidences suggested that cardiac dysfunction and subsequent heart failure are mainly caused by vascular toxicity rather than myocardial toxicity. However, not all of the vascular toxicity of cancer therapies can be explained by obstructive coronary artery disease. In the past few decades, it has been found that myocardial ischemia may be caused by structural or functional disorders of the complex vascular network that cannot be seen by coronary angiography, known as coronary microvascular dysfunction (CMD). There is growing evidences that cancer therapy-related cardiovascular dysfunction (CTRCD) and CMD have many common pathophysiological mechanisms. This paper elucidates the relationship between CTRCD and CMD from the pathophysiological perspective, providing reference for exploring new diagnostic methods and treatment strategies of cardiovascular diseases.

Therapy-related myeloid neoplasms after successful treatment for acute promyelocytic leukemia: a report of four cases and literature review / 中华血液学杂志

Objective@#To investigate the clinical characteristics, diagnosis, treatment and prognosis of therapy-related myeloid neoplasms (t-MNs) after successful treatment for acute promyelocytic leukemia (APL) .@*Methods@#Clinical data of 4 patients, diagnosed as t-MNs secondary to APL at Hematology Hospital of Chinese Academy of Medical Sciences from October 2012 to January 2019, were collected retrospectively. T-MNs related literature was reviewed.@*Results@#The 4 cases were all females, with the median age 42 (range 40-53) years old at the diagnosis of APL. Regarding the induction and consolidation regimens, 3 patients received all-trans retinoid acid (ATRA) and arsenic trioxide (ATO) combined with anthracycline/anthraquinone and/or cytosine. One patient only received ATRA and other auxiliary drugs. Alkylating agents were not administrated. The 4 patients developed t-MNs 40 to 43 months after complete remission (CR) of APL, including 1 case of therapy-related myelodysplastic syndrome (t-MDS) and 3 cases of acute myeloid leukemia (t-AML) . The PML-RARα fusion genes were all negative when t-MNs developed. The three patients with t-AML were treated with 3 to 4 re-induction regimens, one of whom underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission (CR) . One patient with t-MDS received hypomethylating agents. After a median follow-up of 54.5 (48-62) months, 2 patients with t-AML died, the median overall survival after t-MN was 12 (5-18) months. From 1989 to 2018, a total of 63 t-MN cases were reported in the literature. Therefore, 67 cases were analyzed when four patients in our center were added, including 27 males and 40 females with median age 52.5 (15-76) years. The median latency was 39 (12-126) months and the median overall survival after diagnosis of t-MN was 10 (1-39) months.@*Conclusions@#Although rare, t-MNs may occur after successful control of APL. There are no existing guidelines for prevention and treatment of t-MNs, which have very poor prognosis. If cytopenia or other abnormalities of peripheral blood cells develop after 3 years of APL, t-MNs should be considered as a differential diagnosis.

Therapy-related myeloid neoplasms after successful treatment for acute promyelocytic leukemia: a report of four cases and literature review / 中华血液学杂志

Objective: To investigate the clinical characteristics, diagnosis, treatment and prognosis of therapy-related myeloid neoplasms (t-MNs) after successful treatment for acute promyelocytic leukemia (APL) . Methods: Clinical data of 4 patients, diagnosed as t-MNs secondary to APL at Hematology Hospital of Chinese Academy of Medical Sciences from October 2012 to January 2019, were collected retrospectively. T-MNs related literature was reviewed. Results: The 4 cases were all females, with the median age 42 (range 40-53) years old at the diagnosis of APL. Regarding the induction and consolidation regimens, 3 patients received all-trans retinoid acid (ATRA) and arsenic trioxide (ATO) combined with anthracycline/anthraquinone and/or cytosine. One patient only received ATRA and other auxiliary drugs. Alkylating agents were not administrated. The 4 patients developed t-MNs 40 to 43 months after complete remission (CR) of APL, including 1 case of therapy-related myelodysplastic syndrome (t-MDS) and 3 cases of acute myeloid leukemia (t-AML) . The PML-RARα fusion genes were all negative when t-MNs developed. The three patients with t-AML were treated with 3 to 4 re-induction regimens, one of whom underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission (CR) . One patient with t-MDS received hypomethylating agents. After a median follow-up of 54.5 (48-62) months, 2 patients with t-AML died, the median overall survival after t-MN was 12 (5-18) months. From 1989 to 2018, a total of 63 t-MN cases were reported in the literature. Therefore, 67 cases were analyzed when four patients in our center were added, including 27 males and 40 females with median age 52.5 (15-76) years. The median latency was 39 (12-126) months and the median overall survival after diagnosis of t-MN was 10 (1-39) months. Conclusions: Although rare, t-MNs may occur after successful control of APL. There are no existing guidelines for prevention and treatment of t-MNs, which have very poor prognosis. If cytopenia or other abnormalities of peripheral blood cells develop after 3 years of APL, t-MNs should be considered as a differential diagnosis.

Dismal outcome of therapy-related myeloid neoplasm associated with complex aberrant karyotypes and monosomal karyotype: a case report

Introduction: Individuals who are exposed to cytotoxic agents are at risk of developing therapyrelated myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in stratifying patients into different risk groups and thus predict the response to treatment and overall survival. Case report: A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission. Four years later, the disease relapsed and he was given idarubicin, mitoxantrone and ATRA followed by maintenance chemotherapy (ATRA, mercaptopurine and methotrexate). He achieved a second remission for the next 11 years. During a follow-up later, his full blood picture showed leucocytosis, anaemia and leucoerythroblastic picture. Bone marrow examination showed hypercellular marrow with trilineage dysplasia, 3% blasts but no abnormal promyelocyte. Fluorescence in-situ hybridisation (FISH) study of the PML/RARA gene was negative. Karyotyping result revealed complex abnormalities and monosomal karyotype (MK). A diagnosis of therapy-related myelodysplastic syndrome/myeloproliferative neoplasm with unfavourable karyotypes and MK was made. The disease progressed rapidly and transformed into therapy-related acute myeloid leukaemia in less than four months, complicated with severe pneumonia. Despite aggressive treatment with antibiotics and chemotherapy, the patient succumbed to the illness two weeks after the diagnosis. Discussion and Conclusion: Diagnosis of t-MN should be suspected in patients with a history of receiving cytotoxic agents. Karyotyping analysis is crucial for risk stratification as MK in addition to complex aberrant karyotypes predicts unfavourable outcome. Further studies are required to address the optimal management for patients with t-MN.

A Case of Coexistence of Bone Marrow-involved Refractory Marginal Zone B-Cell Lymphoma and Therapy-related Myelodysplastic Syndrome

Recent advances in chemotherapy have led to increased survival rates for patients with hematologic malignancies. However, standard chemotherapies, including alkylating agents for non-Hodgkin lymphoma, could induce therapy-related myeloid neoplasms (t-MNs), a group of disorders categorized by the World Health Organization in 2008. Here, we report a case of coexistence of bone marrow (BM)-involved refractory marginal zone B-cell lymphoma (MZL) and therapy-related myelodysplastic syndrome (t-MDS). Simultaneous presence of refractory lymphoma and t-MN in the BM is rare, and this is the first report in Korea. The patient received allogeneic hematopoietic stem cell transplantation (HSCT) to cure both the MZL and t-MDS. Since the HSCT, he has been stable for 21 months without any evidence of recurrence.

Therapy-related myeloid neoplasms in children and adolescents

BACKGROUND: This retrospective study aimed to characterize and analyze the outcome of therapy-related myeloid neoplasms (t-MNs) in children and adolescents. METHODS: The medical records of 16 patients under 21 years of age at the time of t-MN diagnosis were reviewed. RESULTS: The median patient age was 11.5 years (range, 1.6–20.4 yr). Twelve patients had therapy-related acute myeloid leukemia, 3 patients had myelodysplastic syndrome, and 1 patient had chronic myelomonocytic leukemia. The median latency period was 29 months (range, 11–68 mo). Fourteen patients had cytogenetic aberrations, 8 of whom had an 11q23 abnormality. Of the 13 patients treated with curative intent, 12 patients received myeloid-type induction therapy that led to complete remission (CR) in 8 patients. Nine patients underwent allogeneic transplantation; 4 patients did not undergo transplantation due to chemotherapy-related toxic death (N=3) or parental refusal (N=1). The 5-year overall survival and event-free survival of the 13 patients treated with a curative intent were 46.2% and 30.8%, respectively. For the 9 patients who underwent allogeneic transplantation, the 5-year event-free survival was 66.7%. CONCLUSION: A significant proportion of young patients with t-MNs can experience long-term survival, and allogeneic transplantation plays a key role for attaining cure in these patients.

Myelodysplastic Syndrome (RAEB-II) Development 2 Months after Chemotherapy for a Primary Non-seminomatous Mediastinal Germ Cell Tumor / 대한내과학회지

Here, we report on a 20-year-old patient with a primary nonseminomatous mediastinal germ cell tumor (MGCT) who developed myelodysplastic syndrome (MDS) 2 months following chemotherapy with cisplatin, etoposide, ifosfamide, and paclitaxel. Bone marrow examinations revealed that the MDS was a refractory anemia with excess type II blasts and complex chromosomal abnormalities. With the onset of MDS occurring rapidly following chemotherapy, it is unlikely to have been caused by the therapy. We discuss the association between primary nonseminomatous MGCTs and hematological malignancies, including the possibility of a common clonal origin.

Differentiation of True Recurrence from Delayed Radiation Therapy-related Changes in Primary Brain Tumors Using Diffusion-weighted Imaging, Dynamic Susceptibility Contrast Perfusion Imaging, and Susceptibility-weighted Imaging

PURPOSE: To compare dynamic susceptibility contrast imaging, diffusion-weighted imaging, and susceptibility-weighted imaging (SWI) for the differentiation of tumor recurrence and delayed radiation therapy (RT)-related changes in patients treated with RT for primary brain tumors. MATERIALS AND METHODS: We enrolled 24 patients treated with RT for various primary brain tumors, who showed newly appearing enhancing lesions more than one year after completion of RT on follow-up MRI. The enhancing-lesions were confirmed as recurrences (n=14) or RT-changes (n=10). We calculated the mean values of normalized cerebral blood volume (nCBV), apparent diffusion coefficient (ADC), and proportion of dark signal intensity on SWI (proSWI) for the enhancing-lesions. All the values between the two groups were compared using t-test. A multivariable logistic regression model was used to determine the best predictor of differential diagnosis. The cutoff value of the best predictor obtained from receiver-operating characteristic curve analysis was applied to calculate the sensitivity, specificity, and accuracy for the diagnosis. RESULTS: The mean nCBV value was significantly higher in the recurrence group than in the RT-change group (P=.004), and the mean proSWI was significantly lower in the recurrence group (P<.001). However, no significant difference was observed in the mean ADC values between the two groups. A multivariable logistic regression analysis showed that proSWI was the only independent variable for the differentiation; the sensitivity, specificity, and accuracy were 78.6% (11 of 14), 100% (10 of 10), and 87.5% (21 of 24), respectively. CONCLUSION: The proSWI was the most promising parameter for the differentiation of newly developed enhancing-lesions more than one year after RT completion in brain tumor patients.

Chronic myeloid leukemia as a secondary malignancy after diffuse large B-cell lymphoma

No abstract available.

Therapy-Related Myeloid Neoplasms in 39 Korean Patients: A Single Institution Experience

BACKGROUND: Therapy-related myeloid neoplasms (t-MN) occur as late complications of cytotoxic therapy. This study reviewed clinical and cytogenetic characteristics of patients with t-MN at a single institution in Korea. METHODS: The study subjects included 39 consecutive patients diagnosed with t-MN. Each subject's clinical history of previous diseases, treatments, and laboratory data was reviewed, including cytogenetics. The primary diagnosis was hematologic malignancy in 14 patients and solid tumor in 25 patients. RESULTS: Therapy-related acute myeloid leukemia (t-AML, 66.7%) was found to be more common than therapy-related myelodysplastic syndrome (t-MDS). Primary hematologic malignancies that were commonly implicated included mature B-cell neoplasm and acute leukemia. Breast cancer was the most common primary solid tumor. The mean time interval from cytotoxic therapy initiation to t-MN detection was 49 months. Chromosomal aberrations were observed in 35 patients, and loss of chromosome 5, 7, or both accounted for 41% of all cases. Balanced rearrangements occurred in 13 patients; these patients showed shorter latency intervals (mean, 38 months) than patients with loss of chromosome 5 or 7 (mean, 61 months). CONCLUSIONS: In this study, we determined the clinical and cytogenetic characteristics of Korean patients with t-MN. Although our results were generally consistent with those of previous reports, we found that t-MN resulting from de novo leukemia was common and that t-AML was more common than t-MDS at presentation. Multi-institutional studies involving a larger number of patients and additional parameters are required to investigate the epidemiology, genetic predisposition, and survival rate of t-MN in Korea.

Precursor B-Cell Acute Lymphoblastic Leukemia in Two Patients with a History of Cytotoxic Therapy / 대한내과학회지

Therapy-related myeloid neoplasms have been well characterized. However, precursor B-cell acute lymphoblastic leukemia in patients with prior malignancies is uncommon, and the effect of prior cytotoxic therapy on development of precursor B-cell acute lymphoblastic leukemia is controversial. Therapy-related precursor B-cell acute lymphoblastic leukemia has been reported occasionally. However, cytotoxic therapy-related precursor B-cell acute lymphoblastic leukemia has been reported in Korea only rarely. We herein describe two cases of therapy-related precursor B-cell acute lymphoblastic leukemia.

Neoplasia de boca e orofaringe: um estudo transversal na Fundação Pio XII ? Hospital do Câncer de Barretos, Brasil / Oral and oropharynges neoplasm ? a transversal study in Pio XII Foundation - Cancer Hospital of Barretos, Brazil

Introdução: O câncer bucal representa 5% dos casos da doença no mundo, sendo considerado um problema de saúde pública no Brasil em razão da alta taxa de morbidade e mortalidade dos pacientes. Objetivo: Realizar um estudo transversal dos aspectos clínicos e patológicos de pacientes com câncer de boca e orofaringe da Fundação Pio XII ? Hospital de Câncer de Barretos-SP. Material e método: Foram examinados 292 prontuários de pacientes atendidos no ano de 2008 com diagnóstico de câncer bucal. Foram avaliados os seguintes aspectos: gênero, idade, cor, estado civil, estado de origem, fatores de risco, tipo de neoplasia, sítio da lesão, tratamento oncológico eleito e estadiamento da neoplasia. Resultado: Houve maior ocorrência de câncer de boca e orofaringe em indivíduos procedentes da região sudeste (87%), do gênero masculino (85,3%), de cor branca (72,6%) e acima de 40 anos de idade (97,6%). O carcinoma de células escamosas foi a neoplasia de maior fequência (95,5%), o sítio mais prevalente foi a língua (16,8%), associado ao fumo e ao álcool (38%) e estadiamento tardio (68,5%). Conclusão: O carcinoma de células escamosas foi incidente em áreas adjacentes à língua, com estadiamento IV, em indivíduos do gênero masculino e fumantes, sugerindo forte influência de fatores psicossociais e comportamentais da sociedade moderna na sua ocorrência.

Introduction: Oral cancer accounts for approximately 40% of disease cases worldwide, and given the high morbidity and mortality rates associated with this disease, it has become a public health problem in Brazil. Objective: To do a transversal study of clinic and pathological aspects of oral and oropharynge cancer in patients at the Pio XII Foundation - Cancer Hospital of Barretos-SP, Brazil. Material and method: The health records of 292 patients with oral cancer who received treatment at the Pio XII Foundation - Cancer Hospital of Barretos-SP during 2008 were examined. Gender, age, ethnicity, marital status, state of origin, harmful habits, cancer type, staging of the neoplasm, site of injury, and oncology therapy were explored to determine the prevalence rates of oral cancer associated with these factors. Result: Higher prevalence rates of oral cancer were observed in males (85.3%), aged 40 years or older (97.6%), Caucasians (72.6%), and individuals from the Southeast (87%). Squamous cell carcinoma was the most prevalent neoplasm (95.5%), and it was mostly found on the tongue (16.8%) at later cancer stages (68.5%). It was associated with risk factors such as smoking and alcoholism (38.0%). Conclusion: Stage IV squamous cell carcinoma involving adjacent areas of the tongue in male smokers was frequent, demonstrating the strong influence of psychosocial and behavioral factors on the prevalence of oral neoplasms.

Therapy related myelodysplastic syndrome: A case report and review of literature.

Therapy related myeloid neoplasm is directly related to previous cytotoxic chemotherapy or radiation therapy. We present a 47-year-old lady who developed therapy related myelodysplastic syndrome (MDS) 2.5 years after she received four cycles of chemotherapy and local radiation therapy for carcinoma breast. She presented with bicytopenia with trilineage dyspoiesis in the peripheral blood, bone marrow aspirate and biopsy. Fluorescent in-situ hybridization studies did not reveal any of the common abnormalities associated with MDS. A diagnosis of therapy related MDS was rendered. Different studies have shown that patients treated with alkylating agents and ionizing radiation present as MDS with a latent period of 3-10 years. Our patient developed MDS within 2.5 years of starting chemotherapy and radiotherapy and did not reveal any of the conventional cytogenetic abnormalities. It highlights the importance of simple tests like a complete blood count and peripheral blood smear examination in follow-up of the patients treated with chemotherapy.

A Case of Therapy-related Acute Lymphoblastic Leukemia with t(11;19)(q23;p13.3) and MLL/MLLT1 Gene Rearrangement / 대한진단검사의학회지

Therapy-related ALL (t-ALL) is a rare secondary leukemia that develops after chemotherapy and/or radiotherapy for primary malignancies. Chromosomal 11q23 abnormalities are the most common karyotypic alterations in t-ALL. The t(11;19)(q23;p13) aberration is extremely rare and has not been confirmed at the molecular genetic level. Here, we report a case of t-ALL with t(11;19)(q23;p13.3) and MLL-MLLT1 (alias ENL) gene rearrangement confirmed by cytogenetic analysis, multiplex reverse transcription-PCR (multiplex RT-PCR), and DNA sequencing in a patient who had undergone treatment for breast cancer. A 40-yr-old woman developed acute leukemia 15 months after undergoing 6 cycles of adjuvant chemotherapy (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2), radiation therapy (dose, 5,900 cGy), and anticancer endocrine therapy with tamoxifen. The complete blood cell counts and bone marrow examination showed increased blasts and the blasts showed B lineage immunophenotype (positive for CD19, CD34, and cytoplasmic CD79a). Cytogenetic analysis revealed the karyotype 47,XX,+X,t(11;19)(q23;p13.3)[4]/46,XX[16]. FISH analyses, multiplex RT-PCR, and DNA sequencing confirmed the MLL-MLLT1 gene rearrangement. The patient underwent induction chemotherapy with fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) and achieved complete remission. Subsequently, she underwent consolidation chemotherapy, but died of brain ischemia in the pons and the region of the middle cerebral artery. To our knowledge, this is the first case report of t-ALL with t(11;19)(q23;p13.3) and the MLL-MLLT1 gene rearrangement.

A Case of Therapy-related Myeloid Neoplasm after Successful Treatment of Acute Promyelocytic Leukemia

Acute promyelocytic leukemia (APL) is considered as a curative disease after combined chemotherapy based on all-trans retinoic acid (ATRA) and anthracycline. However, as long-term survivors continue to increase, reports on sporadic cases of therapy-related myeloid neoplasm (t-MN) after successful APL treatment are also increasing. Recently, we have experienced one patient who developed t-MN 7 yr after APL diagnosis. Even though he had not been exposed to alkylating agents at all, he showed alkylating agents-associated features such as long latency period (>5 yr), first presentation as myelodysplatic phase (multilineage dysplasia with increased blasts), and complex karyotype including monosomy 5 and 7. He received only supportive care and expired 3 months after the diagnosis of t-MN (6 months of survival after the onset of cytopenias). t-MN after complete remission of APL is a rare but fatal complication, and patients with complex karyotypes show ominous prognosis in particular. For the early diagnosis of t-MN, long-term and close monitoring of the patient is needed. One should suspect this late complication whenever any unknown cytopenia develops, and should perform bone marrow biopsy and cytogenetic analysis.

Therapy-related acute leukemia in breast cancer patients: twelve cases treated with a topoisomerase inhibitor

BACKGROUND: Therapy-related myeloid neoplasm (t-MN) is a distinct class of acute myeloid leukemia (AML) in the World Health Organization (WHO) classification. Both AML and acute lymphoblastic leukemia (ALL) may develop after treatment for primary cancer. Topoisomerase inhibitors are commonly used to treat breast cancer patients and are well-known for their effect on leukemogenesis of therapy-related acute leukemias (t-AL). METHODS: We retrospectively evaluated bone marrow test results, chromosomal findings, and clinical characteristics of 12 patients who received topoisomerase inhibitors for breast cancer treatment and later developed acute leukemia. RESULTS: Fourteen patients (0.2%) developed t-AL after treatment for breast cancer. Topoisomerase inhibitors were administered to 12 patients. Among them, 9 patients (75%, 9/12) were diagnosed with therapy-related AML (t-AML) and 3 patients (25%, 3/12) with therapy-related ALL (t-ALL). Eight patients (67%, 8/12) showed translocation involving 11q23 and 3 different partner genes, 19p13.1 (37.5%, 3/8), 9p22 (37.5%, 3/8), and 4q21 (25%, 2/8). The median interval between completion of chemotherapy for breast cancer and occurrence of t-AL was 25 months. Patients with 11q23 translocation showed markedly poorer event-free survival than the group without involvement of 11q23. CONCLUSION: The incidence rate of t-AL after treatment for breast cancer was 0.2% in a tertiary hospital in Korea. Translocation involving the MLL gene was frequently found in t-AL caused by a topoisomerase inhibitor and was related to poor prognosis.

A Case of Therapy-related Acute Myeloid Leukemia associated with inv(16) / 대한진단검사의학회지

The inv(16)(p13q22) is found in de novo AML and is closely associated with the FAB subtype M4eo. The inv(16) is rarely reported in therapy-related AML (t-AML) patients. Herein, we report a case of t-AML with inv(16) after combination chemotherapy using antimitotic agent and alkylating agent (cis-platin-paclitaxel) for ovarian serous cystadenocarcinoma.