Favorable Radiographic Response in a Patient With an Oligodendroglioma Treated With Azacitidine and Venetoclax for Acute Myeloid Leukemia.

The standard chemotherapy for treating oligodendrogliomas consists of a combination of procarbazine, lomustine, and vincristine (PCV). The combination of hypomethylating agents like azacitidine and BCL2 inhibitors like venetoclax has not been formally studied in the treatment of glial tumors. The combination of these two drugs is commonly used to treat acute myeloid leukemia (AML), with IDH-mutant disease being a particularly sensitive subtype. The use of azacitidine for the treatment of IDH-mutant gliomas has been reported in the literature, with mixed results that might suggest at least some benefits in a subtype of patients. It is also reported in the literature that the BCL2 gene is associated with treatment resistance and tumor recurrence in gliomas. Here, we present a patient with an oligodendroglioma who was treated with a conventional chemotherapy regimen for AML and, at the same time, had a favorable radiographic response to his brain tumor.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) . Methods: In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed. Results: A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively (P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively (P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively (P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively (P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively (P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively (P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively (P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively (P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively (P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion: There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

Adult rhabdomyosarcoma combined with acute myeloid leukemia: A case report.

BACKGROUND: Rhabdomyosarcoma is a tumor of mesenchymal origin. Secondary leukemia is a complication of previous transformation to other hematologic disorders or is a treatment-related acute myeloid leukemia secondary to cytotoxic chemotherapy or radiation therapy for other malignancies. CASE SUMMARY: We present the case of a 36-year-old female patient who was diagnosed with rhabdomyosarcoma and acute myeloid leukemia. Further disease progression was observed after multiline chemotherapy. Eventually, the patient suffered cerebral hemorrhage, which resulted in death. CONCLUSION: The incidence of rhabdomyosarcoma in adults is extremely low, and secondary leukemia caused by rhabdomyosarcoma is even rarer. Secondary leukemia has a very poor prognosis and a low overall survival rate.

Multiparametric analysis of etoposide exposed mesenchymal stem cells and Fanconi anemia cells: implications in development of secondary myeloid malignancy.

Secondary acute myeloid leukemia (sAML) may develop following a prior therapy or may evolve from an antecedent hematological disorder such as Fanconi Anemia (FA). Pathophysiology of leukemic evolution is not clear. Etoposide (Eto) is a chemotherapeutic agent implicated in development of sAML. FA is an inherited bone marrow (BM) failure disease characterized by genomic instability and xenobiotic susceptibility. Here, we hypothesized that alterations in the BM niche may play a critical/driver role in development of sAML in both conditions. Expression of selected genes involved in xenobiotic metabolism, DNA double-strand break response, endoplasmic reticulum (ER) stress, heat shock response and cell cycle regulation were determined in BM mesenchymal stem cells (MSCs) of healthy controls and FA patients at steady state and upon exposure to Eto at different concentrations and in recurrent doses. Expression of CYPA1, p53, CCNB1, Dicer1, CXCL12, FLT3L and TGF-Beta genes were significantly downregulated in FA-MSCs compared with healthy controls. Eto exposure induced significant alterations in healthy BM-MSCs with increased expression of CYP1A1, GAD34, ATF4, NUPR1, CXCL12, KLF4, CCNB1 and nuclear localization of Dicer1. Interestingly, FA-MSCs did not show significant alterations in these genes upon Eto exposure. As opposed to healthy MSCs DICER1 gene expression and intracellular localization was not altered on FA BM-MSCs after Eto treatment. These results showed that Eto is a highly potent molecule and has pleiotropic effects on BM-MSCs, FA cells show altered expression profile compared to healthy controls and Eto exposure on FA cells shows differential profile than healthy controls.

Patients with secondary acute myeloid leukemia undergoing allogeneic stem-cell transplant have inferior outcomes than de novo acute myeloid leukemia regardless minimal residual disease level by flow cytometry.

Secondary acute myeloid leukemia (s-AML) patients have a poor prognosis and currently the only curative therapy is allogeneic stem-cell transplant (HSCT). However, we do not yet know whether transplantation is sufficient to reverse the poor prognosis compared to de novo AML patients. We analyzed survival after HSCT comparing a cohort of 58 patients with s-AML versus 52 de novo patients who were transplanted between 2012 and 2020. Patients with s-AML had worse event-free survival (EFS) (p = 0.001) and overall survival (OS) (p < 0.001) compared to de novo AML due to an increased risk of relapse (p = 0.06) and non-relapse mortality (p = 0.03). The main difference in survival was observed in patients who achieved complete remission (CR) before HSCT (EFS p = 0.002 OS and <0.001), regardless minimal residual disease (MRD) by |multiparametric flow cytometry cohorts. In patients transplanted with active disease (AD), the prognosis was adverse in both s-AML and de novo AML groups (EFS p = 0.869 and OS p = 0.930). After excluding patients with AD, we stratified the cohort according to conditioning intensity, noticing that s-AML who received MAC had comparable outcomes to de novo AML, but the survival differences remained among reduce intensity conditioning group. In conclusion, transplanted s-AML patients have worse survival among patients in CR before HSCT, regardless of MRD level by flow cytometry compared to de novo AML. MAC patients had similar outcomes irrespective of leukemia ontogeny.

[Treatment responses, outcomes, and prognostic factors associated with them in patients with secondary acute myeloid leukemia].

Objective: To evaluate treatment responses, outcomes, and prognostic factors in adults with secondary acute myeloid leukemia (sAML) . Methods: Between January 2008 and February 2021, date of consecutive cases of younger than 65 years of adults with sAML were assessed retrospectively. Clinical characteristics at diagnosis, treatment responses, recurrence, and survival were evaluated. Logistic regression and Cox proportional hazards model were employed to determine significant prognostic indicators for treatment response and survival. Results: 155 patients were recruited, including 38, 46, 57, 14 patients belonging to t-AML, and AML with unexplained cytopenia, post-MDS-AML, and post-MPN-AML, respectively. In the 152 evaluable patients, the rate of MLFS after the initial induction regimen was 47.4%, 57.9%, 54.3%, 40.0%, and 23.1% in the four groups (P=0.076) . The total rate of MLFS after the induction regimen was 63.8%, 73.3%, 69.6%, 58.2%, and 38.5% (P=0.084) , respectively. Multivariate analysis demonstrated that male gender (OR=0.4, 95% CI 0.2-0.9, P=0.038 and OR=0.3, 95% CI 0.1-0.8, P=0.015) , SWOG cytogenetic classification into unfavorable or intermediate (OR=0.1, 95% CI 0.1-0.6, P=0.014 and OR=0.1, 95% CI 0.1-0.3, P=0.004) and receiving low-intensity regimen as induction regimen (OR=0.1, 95% CI 0.1-0.3, P=0.003 and OR=0.1, 95%CI 0.1-0.2, P=0.001) were typical adverse factors impacting the first CR and the final CR; PLT<45 × 10(9)/L (OR=0.4, 95%CI 0.2-0.9, P=0.038) and LDH ≥258 U/L (OR=0.3, 95%CI 0.1-0.7, P=0.005) were independent factors for CR. Among the 94 patients with achieving MLFS, 46 cases had allogeneic hematopoietic stem cell transplantation. With a median follow-up period of 18.6 months, the probabilities of relapse-free survival (RFS) and overall survival (OS) at 3 years were 25.4% and 37.3% in patients with transplantation, and in patients with chemotherapy, the probabilities of RFS and OS at 3-year were 58.2% and 64.3%, respectively. At the time of achieving MLFS, multivariate analysis revealed that age ≥46 years (HR=3.4, 95%CI 1.6-7.2, P=0.002 and HR=2.5, 95%CI 1.1-6.0, P=0.037) , peripheral blasts ≥17.5% at diagnosis (HR=2.5, 95%CI 1.2-4.9, P=0.010 and HR=4.1, 95%CI 1.7-9.7, P=0.002) , monosomal karyotypes (HR=4.9, 95%CI 1.2-19.9, P=0.027 and HR=28.3, 95%CI 4.2-189.5, P=0.001) were typical adverse factors influencing RFS and OS. Furthermore, CR after induction chemotherapy (HR=0.4, 95%CI 0.2-0.8, P=0.015) and transplantation (HR=0.4, 95%CI 0.2-0.9, P=0.028) were substantially linked to longer RFS. Conclusion: Post-MDS-AML and post-MPN-AML had lower response rates and poorer prognoses than t-AML and AML with unexplained cytopenia. In adults with male gender, low platelet count, high LDH, and SWOG cytogenetic classification into unfavorable or intermediate at diagnosis, and receiving low-intensity regimen as the induction regimen predicted a low response rate. Age ≥46 years, a higher proportion of peripheral blasts and monosomal karyotype had a negative effect on the overall outcome. Transplantation and CR after induction chemotherapy were greatly linked to longer RFS.

'Secondary' acute lymphoblastic/lymphocytic leukemia - done playing second fiddle?

Acute lymphoblastic/lymphocytic leukemia (ALL) occurring post-cancer diagnosis (secondary ALL - sALL) is increasingly recognized as a discrete entity, constituting up to as much as 5-10% of all new ALL diagnoses, and carrying its own biologic, prognostic and therapeutic significance. In this review, we will outline the history and current state of research into sALL. We will explore the evidence for differences underlining its existence as a distinct subgroup, as well as examining what might be driving such differences etiologically, including prior chemotherapy. We will examine these distinctions on population-, chromosomal-, and molecular-levels, and we will consider whether they translate to differences in clinical outcome, and whether they do - or should - warrant differences in treatment selection.

Clinical analysis of leukemia secondary to malignant solid tumor in children / 国际儿科学杂志

Objective:To investigate the clinical characteristics, diagnosis and treatment and prognosis of children with leukemia secondary to malignant solid tumor.Methods:From January 2012 to January 2022, a total of 2 275 children under 15 years of age with malignant solid tumor were admitted to the First Affiliated Hospital of Zhengzhou University.Six children diagnosed with secondary leukemia after follow-up to August 1, 2022 were selected as the study objects.Their clinical data were retrospectively analyzed and the literature was reviewed.Results:(1)A total of 2 275 children with malignant solid tumors included 1 369 males and 906 females.There were 6 children with secondary leukemia, with an incidence rate of 0.26%, including 4 males and 2 females.The age of onset of solid tumor was 5.5(2.8, 9.7)years, and the age of secondary leukemia was(9.1±3.9)years, and the interval between them was(26.2±17.3)months.(2)Malignant solid tumor types: according to the time of secondary leukemia, there were hip malignant rhabdomyoma in 1 case, intracranial medulloblastoma in 2 cases, intracranial and pelvic malignant germinoma in 1 case respectively, and pancreatic blastoma in 1 case.Intracranial lesion biopsy was performed in 1 case, and tumor resection was performed in the other 5 cases.Three patients with intracranial tumors underwent local tumor bed, whole brain and spinal radiotherapy.All the 6 children received chemotherapy, and the main chemotherapy drugs were doxorubicin, vincristine, cyclophosphamide, platinum, ifosfamide, etoposide, bleomycin, temozolomide, etc.Complete remission was achieved in 3 cases, partial remission in 1 case, stable disease in 1 case, and disease progression in 1 case.(3)The secondary leukemia types were as follows: acute myeloid leukemia(AML)M5 in 3 cases, M1 in 1 case, M2 in 1 case, and acute B-lymphoblastic leukemia(B-ALL)in 1 case.All six cases refused hematopoietic stem cell transplantation(HSCT).One case with B-ALL gave up after receiving hydroxyurea and dexamethasone.Five cases with AML received chemotherapy according to the AML-2006 Protocol of Hematology Group of Pediatrics Society of Chinese Medical Association.The outcome of the disease was as follows: 2 cases died early, 4 cases achieved complete remission after 1 ~ 2 courses of chemotherapy, among which 2 cases did not continue treatment after 3 courses of chemotherapy due to pulmonary infection, deep mycosis, osteomyelitis, etc, and then recurred and died.By the end of follow-up, 2 cases survived and continued treatment, of which 1 case relapsed.After the diagnosis of secondary leukemia, the 1-year overall survival rate of the 6 cases was(33±26)%.Conclusion:Leukemia secondary to malignant solid tumors in children is rare and mostly occurs in older children.The pathogenesis is related to genotoxic injury caused by exposure to chemotherapy or radiotherapy, and the prognosis is unfavourable.HSCT after chemotherapy combined with immunotherapy is the best treatment strategy.

Treatment responses, outcomes, and prognostic factors associated with them in patients with secondary acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate treatment responses, outcomes, and prognostic factors in adults with secondary acute myeloid leukemia (sAML) . Methods: Between January 2008 and February 2021, date of consecutive cases of younger than 65 years of adults with sAML were assessed retrospectively. Clinical characteristics at diagnosis, treatment responses, recurrence, and survival were evaluated. Logistic regression and Cox proportional hazards model were employed to determine significant prognostic indicators for treatment response and survival. Results: 155 patients were recruited, including 38, 46, 57, 14 patients belonging to t-AML, and AML with unexplained cytopenia, post-MDS-AML, and post-MPN-AML, respectively. In the 152 evaluable patients, the rate of MLFS after the initial induction regimen was 47.4%, 57.9%, 54.3%, 40.0%, and 23.1% in the four groups (P=0.076) . The total rate of MLFS after the induction regimen was 63.8%, 73.3%, 69.6%, 58.2%, and 38.5% (P=0.084) , respectively. Multivariate analysis demonstrated that male gender (OR=0.4, 95% CI 0.2-0.9, P=0.038 and OR=0.3, 95% CI 0.1-0.8, P=0.015) , SWOG cytogenetic classification into unfavorable or intermediate (OR=0.1, 95% CI 0.1-0.6, P=0.014 and OR=0.1, 95% CI 0.1-0.3, P=0.004) and receiving low-intensity regimen as induction regimen (OR=0.1, 95% CI 0.1-0.3, P=0.003 and OR=0.1, 95%CI 0.1-0.2, P=0.001) were typical adverse factors impacting the first CR and the final CR; PLT<45 × 10(9)/L (OR=0.4, 95%CI 0.2-0.9, P=0.038) and LDH ≥258 U/L (OR=0.3, 95%CI 0.1-0.7, P=0.005) were independent factors for CR. Among the 94 patients with achieving MLFS, 46 cases had allogeneic hematopoietic stem cell transplantation. With a median follow-up period of 18.6 months, the probabilities of relapse-free survival (RFS) and overall survival (OS) at 3 years were 25.4% and 37.3% in patients with transplantation, and in patients with chemotherapy, the probabilities of RFS and OS at 3-year were 58.2% and 64.3%, respectively. At the time of achieving MLFS, multivariate analysis revealed that age ≥46 years (HR=3.4, 95%CI 1.6-7.2, P=0.002 and HR=2.5, 95%CI 1.1-6.0, P=0.037) , peripheral blasts ≥17.5% at diagnosis (HR=2.5, 95%CI 1.2-4.9, P=0.010 and HR=4.1, 95%CI 1.7-9.7, P=0.002) , monosomal karyotypes (HR=4.9, 95%CI 1.2-19.9, P=0.027 and HR=28.3, 95%CI 4.2-189.5, P=0.001) were typical adverse factors influencing RFS and OS. Furthermore, CR after induction chemotherapy (HR=0.4, 95%CI 0.2-0.8, P=0.015) and transplantation (HR=0.4, 95%CI 0.2-0.9, P=0.028) were substantially linked to longer RFS. Conclusion: Post-MDS-AML and post-MPN-AML had lower response rates and poorer prognoses than t-AML and AML with unexplained cytopenia. In adults with male gender, low platelet count, high LDH, and SWOG cytogenetic classification into unfavorable or intermediate at diagnosis, and receiving low-intensity regimen as the induction regimen predicted a low response rate. Age ≥46 years, a higher proportion of peripheral blasts and monosomal karyotype had a negative effect on the overall outcome. Transplantation and CR after induction chemotherapy were greatly linked to longer RFS.

A case of therapy-related acute lymphoblastic leukemia following the treatment of acute myeloid leukemia.

Therapy-related acute lymphoblastic leukemia represents a distinct entity associated with inferior survival compared with de novo acute lymphoblastic leukemia. It consists of a subset of patients who have had exposure to chemotherapy or radiation for a previous malignancy. Here, we describe a case of acute myeloid leukemia who later developed precursor B cell acute lymphoblastic leukemia and discuss the current relevant literature. Our case highlights the importance of classifying therapy-related acute lymphoblastic leukemia as a separate as entity based on its biologic and clinical features.

Role of radiotherapy and chemotherapy in the risk of leukemia after childhood cancer: An international pooled analysis.

Childhood cancer survivors are at increased risk for second primary leukemia (SPL), but there is little consensus on the magnitude of some risk factors because of the small size of previous studies. We performed a pooled analysis of all published studies with detailed treatment data, including estimated active bone marrow (ABM) dose received during radiation therapy and doses of specific chemotherapeutic agents for childhood cancer diagnosed from 1930 through 2000, in order to more thoroughly investigate treatment-related risks of SPL. A total of 147 SPL cases (of which 69% were acute myeloid leukemia [AML]) were individually matched to 522 controls, all from four case-control studies including patients from six countries (France, United Kingdom, United States, Canada, Italy and Netherlands). Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were calculated using conditional logistic regression, and the excess OR per Gray (EOR/Gy) was also calculated. After accounting for the other therapies received, topoisomerase II inhibitor was associated with an increased SPL risk (highest tertile vs none: OR = 10.0, 95% CI: 3.7-27.3). Radiation dose to the ABM was also associated with increased SPL risk among those not receiving chemotherapy (EOR/Gy = 1.6, 95% CI: 0.1-14.3), but not among those who received chemotherapy (CT). SPL were most likely to occur in the first decade following cancer treatment. Results were similar when analyses were restricted to AML. The evidence of interaction between radiation and CT has implications for leukemogenic mechanism. The results for topoisomerase II inhibitors are particularly important given their increasing use to treat childhood cancer.

Therapy-related myeloid neoplasms in lymphoma survivors: Reducing risks.

Treatment for Hodgkin (HL) and non-Hodgkin's lymphoma (NHL) has changed dramatically in the last fifty years. While there are increasing numbers of long-term survivors, there has been increasing recognition of the long-term toxicities of treatments, particularly therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML). The survival for t-MDS/AML is extremely poor. Multiple heterogeneous retrospective studies have reported risk factors for the development of t-MDS/AML. Chemotherapy and radiation therapy have been most closely examined as possible t-MDS/AML risk factors. In this paper, we will review the risks of t-MDS/AML for HL and NHL patients as reported in the literature and assess for any changes over time. In HL patients, the incidence of t-MDS/AML has decreased with a reduction in alkylating agents. In indolent NHL patients, we anticipate decreased incidence of t-MDS/AML as targeted therapies begin to replace cytotoxic chemotherapy.

Therapy-related myeloid neoplasms: clinical perspectives.

Therapy-related myeloid neoplasms (t-MNs) are a complication of cytotoxic treatment for primary tumors and autoimmune diseases. t-MNs result from a complex interaction between individual predisposition and exposition to toxic agents. Some different biological and clinical characteristics can be recognized according to the type of anticancer drug. Compared to de novo myeloid neoplasms, prognosis of t-MN is dismal. Age and karyotype are the most important prognostic factors for t-MN, which should be treated with frontline chemotherapy treatments that are appropriate for patients with myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML) with similar disease characteristics. Allogeneic stem cell transplantation should be considered particularly for unfavorable karyotypes and younger patients with aggressive disease.

Allogeneic Hematopoietic Stem Cell Transplantation In Therapy-Related Myeloid Neoplasms (t-MN) of the Adult: Monocentric Observational Study and Review of the Literature.

BACKGROUND: Therapy related myeloid neoplasms (t-MN) occur due to direct mutational events of chemotherapeutic agents and radiotherapy. Disease latency, mutational events and prognosis vary with drugs categories. METHODS: We describe a cohort of 30 patients, 18 females and 12 males, with median age of 52.5 years (range, 20 to 64), submitted to allogeneic stem cell transplantation (HSCT) in our department between September 1999 and March 2017. Patients had a history of solid tumour in 14 cases, haematological disease in 15 cases and both of them in one case. After a median of 36.5 months (range, 4 to 190) from first neoplasm, patients developed t-AML in 19 cases and t-MDS in 11 cases. Molecular abnormalities were detected in 5 patients, while karyotype aberrations were found in 17 patients. Patients received conventional chemotherapy in 14 cases, azacitidine in 10 cases and both of them in one case. Five patients were submitted to HSCT without previous treatment except for supportive therapy. RESULTS: Seventeen patients obtained sustained CR after SCT, while 8 patients showed resistant or relapsed disease. The remaining five patients died early after SCT. At follow up time (May 2017) 13 patients were alive with a median OS of 48 months (range 3-195), while 17 patients died after a median of 4 months (range 1-27) by relapse mortality in 6 cases and non-relapse mortality in the other 11 patients. CONCLUSIONS: Global OS was 43%. After SCT, 72.2% of patients with t-MN maintained a sustained CR.

A Case of Therapy-related Acute Myeloid Leukemia Following Treatment with 5-Fluorouracil.

Therapy-related acute myeloid leukemia (t-AML) is most frequently observed after the use of alkylating agents and topoisomerase II inhibitors and is associated with the frequent occurrence of high-risk karyotypes, poor prognosis, and distinct clinical behavior. Therefore, identifying therapy-related causation among patients with newly diagnosed acute leukemia is of great interest. We report the case of a patient who developed therapy-related acute myeloid leukemia after exposure to antimetabolite chemotherapy and emphasize the importance of identifying genetic alterations when the possibility of a therapy-related origin arises.

Acanthamoeba granulomatous amoebic encephalitis after pediatric hematopoietic stem cell transplant.

Acanthamoeba encephalitis is a rare, often fatal condition, particularly after HSCT, with 9 reported cases to date in the world literature. Our case was originally diagnosed with ALL at age 3 years, and after several relapses underwent HSCT at age 9 years. At 17 years of age, he was diagnosed with secondary AML for which he underwent a second allogeneic HSCT. He presented with acute-onset worsening neurological deficits on day +226 after the second transplant and a post-mortem diagnosis of Acanthamoeba encephalitis was established, with the aid of the CDC.

Development of acute myeloid leukemia in patients with untreated chronic lymphocytic leukemia.

The development of acute myeloid leukemia (AML) in patients with untreated chronic lymphocytic leukemia (CLL) is rare. We experienced a 65-year-old man who developed AML with aberrant CD7 expression and monoallelic CEBPA mutation during watchful waiting for CLL. He failed to achieve complete response (CR) by standard induction therapy for AML. We retrospectively reviewed 27 patients who developed AML with untreated CLL published between 1973 and 2016. The median age at diagnosis of AML was 68 years, and the median duration between the diagnoses of AML and CLL was 4.2 years. Diagnosis of AML and CLL was made simultaneously in 16 patients. The CR rate of AML was 42.9%, and the median survival was only 1.5 months after the diagnosis of AML. Patients who achieved CR tended to survive longer than those who did not. Our results demonstrated that the development of AML in patients with untreated CLL was associated with a poor response to chemotherapy and an extremely poor prognosis.

Secondary acute lymphoblastic leukemia is an independent predictor of poor prognosis.

Compared to secondary acute myeloid leukemia, secondary acute lymphoblastic leukemia (sALL) is poorly characterized. We utilized data from the Surveillance, Epidemiology, and End Results (SEER) 13 database to further elucidate patient characteristics and prognostic factors in sALL. Cases of adult de novo acute lymphoblastic leukemia (ALL) and sALL in patients with primary breast, rectum, cervix, or ovarian cancers or lymphoma with a latency period of at least 12 months were identified within the SEER 13 database. Survival in sALL and de novo ALL were compared after propensity matching based on age, gender, race, ALL subtype, and year of diagnosis. 4124 cases of de novo ALL and 79 cases of sALL were identified. sALL patients were older at diagnosis (median 62 years vs. 44 years; p<0.01). Overall survival (OS) in sALL was lower than de novo ALL (median 8 months vs. 11 months), 1 year OS: 35% vs. 47% (p=0.05), 2 year OS: 16% vs. 31% (p<0.01), and 5 year OS: 7% vs. 21% (p<0.01). Multivariate analysis revealed sALL as an independent predictor of worsened survival (adjusted HR 1.54; 95% CI 1.16-2.04, p<0.01) after propensity matching.