Carrimycin in the treatment of acute promyelocytic leukemia combined with pulmonary tuberculosis: A case report

BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for acute promyelocytic leukemia(APL)combined with PTB is lacking.These patients show an extremely poor prognosis.Therefore,studies should establish efficient treatment options to improve patient survival and prognosis.CASE SUMMARY A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our hospital.Peripheral blood smear revealed 54%blasts.Following bone marrow examinations,variant APL with TNRC18-RARA fusion gene was diagnosed.Chest computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions,partial atelectasis in the lower lobes of both lungs,and the bronchoalveolar lavage fluid gene X-Pert test was positive,indicative of PTB.Carrimycin,ethambutol(EMB),and isoniazid(INH)were administered since he could not receive chemotherapy as the WBC count decreased continuously.After one week of treatment with carrimycin,the patient recovered from fever and received chemotherapy.Chemotherapy was very effective and his white blood cells counts got back to normal.After being given five months with rifampin,EMB and INH and chemotherapy,the patient showed complete remission from pneumonia and APL.CONCLUSION We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy.

CD71-mediated liposomal arsenic-nickel complex combined with all-trans retinoic acid for the efficacy of acute promyelocytic leukemia

Clinically,arsenic trioxide(ATO)was applied to the treatment of acute promyelocytic leukemia(APL)as a reliable and effective frontline drug.However,the administration regimen of AsⅢwas limited due to its fast clearance,short therapeutic window and toxicity as well.Based on CD71 overexpressed on APL cells,in present study,a transferrin(Tf)-modified liposome(LP)was established firstly to encapsulate AsⅢin arsenic-nickel complex by nickel acetate gradient method.The AsⅢ-loaded liposomes(AsLP)exhibited the feature of acid-sensitive release in vitro.Tf-modified AsLP(Tf-AsLP)were specifically taken up by APL cells and the acidic intracellular environment triggered liposome to release AsⅢwhich stimulated reactive oxygen species level and caspase-3 activity.Tf-AsLP prolonged half-life of AsⅢin blood circulation,lowered systemic toxicity,and promoted apoptosis and induced cell differentiation at lesion site in vivo.Considering that ATO combined with RA is usually applied as the first choice in clinic for APL treatment to improve the therapeutic effect,accordingly,a Tf-modified RA liposome(Tf-RALP)was designed to reduce the severe side effects of free RA and assist Tf-AsLP for better efficacy.As expected,the tumor inhibition rate of Tf-AsLP was improved significantly with the combination of Tf-RALP on subcutaneous tumor model.Furthermore,APL orthotopic NOD/SCID mice model was established by 60CO irradiation and HL-60 cells intravenously injection.The effect of co-administration(Tf-AsLP+Tf-RALP)was also confirmed to conspicuous decrease the number of leukemia cells in the circulatory system and prolong the survival time of APL mice by promoting the APL cells’apoptosis and differentiation in peripheral blood and bone marrow.Collectively,Tf-modified acid-sensitive AsLP could greatly reduce the systemic toxicity of free drug.Moreover,Tf-AsLP combined with Tf-RALP could achieve better efficacy.Thus,transferrinmodified AsⅢliposome would be a novel clinical strategy to improve patient compliance,with promising translation prospects.

Atypical Hemolytic Uremic Syndrome in a Patient with Acute Promyelocytic Leukemia: A Case Report

Introduction: Acute Promyelocytic Leukemia (APL) is highly associated with hemostasis alterations. The atypical hemolytic uremic syndrome (aHUS) is a rare type of Thrombotic Microangiopathy (TMA) due to an overactivation of the alternative complement pathway. Case Presentation: A 48-years-old woman was diagnosed with APL and achieved molecular remission after induction therapy. During the second consolidation cycle she presented with TMA. She began treatment with plasma exchange plus corticotherapy but due to aggravation of symptoms Eculizumab was initiated. Thrombotic thrombocytopenic purpura, infections and drug toxicity causes were ruled out. There was no evidence of relapse of the APL. Genetic studies of the hereditary anomalies of the alternative complement pathway were negative and the decision of stopping Eculizumab was made. During maintenance therapy for the APL she presented a severe relapse of the aHUS, requiring dialysis. She re-started treatment with Eculizumab with a progressive hematologic recovery and improvement of renal function. She completed APL treatment without relapse of the leukemia for the moment and continues to be treated with Eculizumab. Conclusion: This is the first published case of coexisting aHUS and APL successfully treated with Eculizumab.

In vitro study on arsenic sulfide (realgar)-induced apoptosis of retinoic acid susceptible or resistant acute promyelocytic leukemia cell lines

Objective: To further understand the possible mechanisms of arsenic sulfide (realgar) in the treatment of acute promyelocytic leukemia (APL). Methods: All-trans retinoic acid (ATRA)-susceptible APL cell line (NB4 cells) and ATRA-resistant APL cell line (MR2 subclone) were used as models in vitro. At various times after incubated with various concentrations of realgar, NB4 and MR2 cells were observed by cell viability , cell proliferation and cell morphology; cell cycle and the expression of Annexin V were assayed by flow cytometry. Results: Cell viability and proliferation of NB4 and MR2 cells were inhibited after the treatment, to some extent, in a dose and time dependent manner. 177 - 711g/L of realgar treated NB4 and MR2 cell presented morphologically some features of apoptotic cells such as intact cell membrane, chromatin condensation and nuclear fragmentation, apoptosis body could be found by electron microscopy as well. Sub-Gl cells and cell cycle arrest were observed by flow cytometry. The proportion of Annexin V -FITC+/PI cells , which represent apoptotic cells, was up-regulated. Conclusion: Realgar could induce apoptosis of acute promyelocytic leukemia cell despite its susceptibility to retinoic acid in the way that may be different from retinoic acid.

Successful treatment of relapsed acute promyelocytic leukemia with arsenic trioxide in a hemodialysis-dependent patient: A case report

BACKGROUND Arsenic trioxide(ATO)is recommended for patients who do not achieve molecular remission or who have molecular or morphologic relapse.However,there are no guidelines for adjusting ATO dosage in patients with severe renal failure or on dialysis.Herein,we report the successful treatment of relapsed acute promyelocytic leukemia(APL)in a patient on hemodialysis with ATO single agent and review the cases in literature.CASE SUMMARY A 46-year-old woman who has been on hemodialysis to chronic glomerulonephritis for 15 years visited our hospital for pancytopenia.She had been seen for pancytopenia 3 years ago and had been diagnosed with APL.She also received chemotherapy for APL but unfortunately was lost to follow-up after her second consolidation chemotherapy.She was noted to have pancytopenia by her nephrologist during hemodialysis 1 mo ago.Bone marrow biopsy and reverse transcriptase-polymerase chain reaction(RT-PCR)tests revealed a diagnosis of relapsed APL.Treatment for relapsed APL with ATO single agent was started and she achieved molecular remission after administering 24 doses of ATO.Thus far,four consolidation therapies have been performed with the ATO single agent,and,to date,the molecular remission has been maintained as negative promyelocytic leukemia/retinoic acid receptor-αfusion gene as confirmed by RTPCR testing for two years.CONCLUSION This is a rare case of relapsed APL successfully treated with the single agent ATO in a patient on hemodialysis.

Pediatric acute myeloid leukemia patients with i(17)(q10)mimicking acute promyelocytic leukemia:Two case reports

BACKGROUND Chromosome i(17)(q10)abnormality is mainly associated with chronic myeloid leukemia(CML),myelodysplastic syndrome/myeloproliferative tumors(MDS/MPD),and acute myeloid leukemia(AML).The role of i(17)(q10)in AML is still unknown,the differences between AML and acute promyelocytic leukemia(APL)-like AML with i(17)(q10)need more research.This study aimed to investigate the clinical characteristics and laboratory evidence of 2 AML cases with i(17)(q10),similar to APL phenotype.CASE SUMMARY Both pediatric patients were males;case 1 had newly diagnosed AML,and case 2 showed relapsed tumor after 1 year of drug withdrawal.Bone marrow cell morphology,chromosome karyotype analysis,Fully-instrumented submersible housing test,immunological assays,molecular biological methods,and blood tumor panoramic gene test were performed.All-trans retinoic acid(ATRA)combined with arsenic acid(As2O3)were used in the first course of treatment.Bone marrow was dominated by abnormal promyelocytic granulocytes.Karyotype test revealed i(17)(q10)isochromosome.Immunological phenotype mainly included positive expressions of CD9,CD13,CD33,and CD38.Case 1 suffered intracranial hemorrhage after re-chemotherapy and died on D162.For case 2,on D145 and D265,bone marrow promyelocytic granulocytes accounted for 2%.Flow cytometric residual lesion detection showed no abnormal immunophenotype cells.The copy number of WT1 gene in two cases were 1087 and 1010,respectively,and the expression rates were 55.29% and 59.5%,respectively.CONCLUSION ATRA,As2O3,and chemotherapy may be ineffective in treating APL-like AML with i(17)(q10)but without t(15;17)and PML-RARA fusion gene.

Therapy-related acute promyelocytic leukemia with FMS-like tyrosine kinase 3-internal tandem duplication mutation in solitary bone plasmacytoma: A case report

BACKGROUND Therapy-related acute promyelocytic leukemia(t-APL)is a rare complication observed in solitary bone plasmacytoma(SBP),and SBP after radiotherapy evolving to APL harboring the FMS-like tyrosine kinase 3-internal tandem duplication(FLT3-ITD)mutation has never been reported.Here,we present the first case reported until now.CASE SUMMARY We describe a 64-year-old woman who presented with lumbar pain and was initially diagnosed with SBP.However,after one year of radiotherapy treatment,this patient experienced a long-standing bone-marrow-suppressive period and finally developed APL harboring the FLT3-ITD mutation,as confirmed by analyses of clinical features,bone marrow morphology,flow cytometry,cytogenetic examination,and molecular biology.On admission,the patient had disseminated intravascular coagulation and intracranial hemorrhage,and the peripheral blood and bone marrow smear displayed abundant abnormal promyelocytes.Unfortunately,she died when the definite diagnosis was made.CONCLUSION The patient with t-APL harboring FLT3-ITD mutation evolving from SBP after radiotherapy had not been reported and had poor clinical outcomes.FLT3-ITD mutation in t-APL may be a potential pathogenesis of leukemogenesis.We should consider the potential risk of secondary neoplasms in SBP patients after radiotherapy.

LEUKOCYTOSIS AND RETINOIC ACID SYNDROME IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA TREATED WITH ARSENIC TRIOXIDE

Objective To study the incidence of leukocytosis and retinoic acid （RA） syndrome in newly diagnosed and relapsed acute promyelocytic leukemia （APL） patients treated with arsenic trioxide （ATO）. Methods Thirty patients with newly diagnosed or relapsed APL received ATO for remission induction at the dose of 10 mg/d. RA syndrome was defined when patient was with one or more of the following signs or symptoms： fever, dyspnea, serous cavity effusion, muscular pain, pulmonary infiltration, weight gain, or pulmonary infiltration on chest X-ray. Results Twenty-three （77%） patients achieved complete remission, mean time to remission was 37. 1 days. Leukocytosis was observed in 14 （47%） patients, mean time to leukocytosis was 12. 7 days, median baseline leukocyte count for patients with leukocytosis was 3.1 x 109/L, which was higher than that for patients who did not de,.＇elop leukocytosis （2.6 × 10^9/L, z = - 2. 635, P = 0. 008）. No other cytotoxic therapy was administered, and the leukocytosis resolved in all cases. The RA syndrome was observed in 9 （30%） patients, mean time to diagnose of RA syndrome was 13.9 days, median baseline leukocyte count for patients with RA syndrome was 3.6 × 10^9/L, which was higher than that for patients who did not develop RA syndrome （2. 6 × 10^9/L, z = - 1. 909, P =0. 046）. No patient died of RA syndrome. Conclusion Leukocytosis and RA syndrome are associated with ATO and baseline leukocyte count respectively, and there is distinct link between leukocytosis and RA syndrome.

All-trans Retinoic Acid,Arsenic Trioxide,and Anthracycline-based Chemotherapy Improves Outcome in Newly Diagnosed Acute Promyelocytic Leukemia Regardless of FLT3-ITD Mutation Status

All-trans retinoic acid(ATRA)and pre-upfront arsenic trioxide(ATO)have revolutionized the therapy of acute promyelocytic leukemia(APL).However,internal tandem duplication of FMS-like tyrosine kinase 3(FLT3-ITD)mutations is associated with increased risk of relapse.The aim of this study was to analyze the prognostic impact of FLT3-ITD on APL patients who received remission induction with ATRA,idarubicin(IDA)and/or ATO,followed by ATRA plus ATO along with anthracycline,as consolidation therapy.A total of 72 patients newly diagnosed with APL were included in this study.83.3%of the patients achieved complete remission(CR)after induction therapy.FLT3-ITD mutations were detected in 16(22.2%)patients and closely related to bcr-3 PML-RARa transcript(P<0.001).The 5-year overall survival(OS)rate was 100%in both FLT3-ITDposltlve and FLT3-ITD^(negatlve)groups,and there was no significant difference in 5-year event-free survival(EFS)between the two groups(78.3%vs.83.3%,P=0.85).ATRA plus ATO and anthracycline-based chemotherapy achieved great outcome in newly diagnosed APL regardless of the FLT3-ITD mutation status.

Myeloid sarcoma of the colon as initial presentation in acute promyelocytic leukemia:A case report and review of the literature

BACKGROUND Myeloid sarcoma(MS)rarely occurs in acute promyelocytic leukemia(APL)at onset,but it can develop in relapse cases,especially after APL treated with alltrans retinoic acid(ATRA).Therefore little is known about the clinical features and suitable treatment for APL related MS due to the rarity of the disease,although this may be different from the treatment and prognosis of MS in the relapse stage.To our best knowledge,this is the second case report of APL initial presentation as colon MS.CASE SUMMARY A 77-year-old woman complained of intermittent right lower abdominal pain,black stool,and difficult defecation for 2 mo.Physical examination showed diffuse tenderness during deep palpation and an anemic appearance.Laboratory findings showed positivity for fecal occult blood testing;white blood cell count:3.84×109/L;hemoglobin:105 g/L;platelet count:174×109/L;and negativity for tumor markers.Abdominal enhanced computed tomography showed a space occupying lesion in the colon(1.9 cm).Fibrocolonoscopy revealed a polypoid and ulcerated mass measuring 2.5 cm.The tumor was removed.To our surprise,MS was confirmed by immunohistochemistry.PML/RARαfusion gene was detected in colon specimens by fluorescent in situ hybridization and real-time reverse transcription polymerase chain reaction,which was consistent with the bone marrow.She was diagnosed as having APL related MS.A smooth and unobstructed intestinal wall was found by fibrocolonoscopy,and continuous molecular remission was confirmed in both the bone marrow and colon after four courses of ATRA+arsenic trioxide(ATO).ATRA+ATO showed a favorable therapeutic response for both APL and MS.CONCLUSION Early use of ATRA can benefit APL patients,regardless of whether MS is the first or recurrent manifestation.

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.

CYTOKINE SECRETION IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA AFTER TREATMENT WITH ALLTRANS RETINOIC ACID

ABSRTACT Objective: To detect the modulation of cytokines production by acute promyelocytic leukemia (APL) cells before or after exposure to all-trans retinoic acid (ATRA). Methods: Diagnoses were performed according to the FAB cytological classification criteria and cytogenetic criteria. Bone marrow or blood samples from APL patients were collected in heparinized microfuge tube. Primary APL cells were separated and purified by traditional Ficoll-Hypaque density centrifugation and enriched after adherence to plastic surfaces. IL-1b, IL-6, IL-8, TNFa and G-CSF levels in the supernatants of cultured leukemia cells were estimated by ELISA method. NBT method was used to detect the differentiation of APL cells at the same time. Results: 96 h after exposure to ATRA at 10-6 M in vitro or 60 mg/day in vivo, APL cells showed a significant increase of IL-1b (P<0.05) and G-CSF (P<0.05) production, and a significant decrease of IL-6 (P<0.05) and IL-8 (P<0.05), however, there was no obvious variation of TNFa. On the other hand, the proliferation of APL cells in vitro was statistically correlated to the IL-1b secretion or G-CSF secretion. And the cell number ratio in patients with detectable IL-1b or G-CSF was higher than that without detectable IL-1b or G-CSF. Conclusion: IL-1b and G-CSF secretion may play an important role in the proliferation of APL cells after exposure to ATRA.

Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia

Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient population.The present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients.Methods:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were evaluated.In addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL.Results:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor growth.Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations.Conclusion:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.

Distribution and clonality of peripheral blood TCR Vα subfamily T cells in patients with acute promyelocytic leukemia

Objective： To investigate the distribution and clonality of TCR Va subfamily T cells in patients with acute promyelocytic leukemia （APL）. Methods： The complementary determining region 3 （CDR3） of TCR Va 29 subfamily genes in peripheral blood mononuclear cells from 9 APL patients were amplified using RT-PCR. The positive products were further analyzed to identity the clonality of T cells by GeneScan technique. Results： One to seven of TCR Va subfamilies could be detected in peripheral blood T cells from 9 cases with APL, the frequent expression of Va subfamilies predominated in Vα3 and Va19. Clonal expanded T cells could be detected in 8 APL patients, which predominant used Va3, Va26 or Va27 （3 out of 8 cases）. However, almost all Va subfamilies with polyclonal expansion could be detected in peripheral blood T cells from 10 cases of normal individuals. Conclusion： Remarkable skew distribution and clonal expansion of TCR Va subfamilies T cells is the common feature in patients with APL. Clonal expansion of T cells might reflect a response in host to APL cell associated antigen, whether these expanded T cells have the ability for specific cytotoxicity against APL cells, remains an open question.

Effect of arsenic sulfide on tissue factor expression in acute promyelocytic leukemia cell lines

Objective: To investigate the effect of arsenic sulfide (tetra-arsenic tetra-sulfide As4S4; diarsenic trisulfide As2S3) on tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia( APL) cell lines ( NB4 and MR2) and the basic mechanism of their role. Methods: NB4 and MR2 cells were respectively treated with As4S4 , As2S3, As4S4 and Cyclohexamide( CHX). PCA of the cells was detected using one-stage clotting assay. TF antigen was detected by ELISA. TF and PML/RARa fusion gene mRNA by semi-quantitive RT-PCR. The PCA and TF antigen of HL-60 and K562 cells were also examined. Results: The PCA and TF antigen level in NB4 and MR2 cells were significantly higher than that in HL-60 and K562 cells. Both As4S4 and As2S3 can down-regulate the TF antigen , TF mRNA transcription and membrane PCA of NB4 and MR2 cells in vitro in a time-dependent manner. The role of As4S4 was stronger than that of As2S3. Both As4S4 and As2S3 had no effect on PML/RARa fusion gene transcription. CHX treatment completely suppressed the down-regulate effect of As4S4 on the TF mRNA expression. Conclusion: As4S4 and As2S3 may down regulate tissue factor expression and PCA of NB4 and MR2 cells. By down-regulating TF expression, As4S4 and As2S3 might be used to improve the DIC-related hemorrhage in APL patients. Elevated TF antigen level of NB4 and MR2 cells may be related to the fusion gene PML/RARa. The modulation of the TF mRNA expression in NB4 and MR2 cells by As4S4 and As2S3 might be indirect and might not involve PML/RARa fusion gene.

Central nervous system recurrence in a patient treated for acute promyelocytic leukemia,resulting in sideroblastic anemia:A case report

BACKGROUND Previous cases that have been stated in this article have displayed that around 1%to 7%of patients that have been treated with chemotherapy for acute promyelocytic leukemia developed myelodysplastic syndrome or acute myeloid leukemia.One can see that’s why this case presentation of a 60-year-old man that had a good response to acute promyelocytic leukemia treatment,that later presented with a central nervous system recurrence of acute promyelocytic leukemia and acquired sideroblastic anemia(a form of myelodysplasia)from treatment is a unique case report.CASE SUMMARY The presence of central nervous system relapse in acute promyelocytic leukemia patients is very unlikely compared to recurring mainly in the bone marrow.It is also uncommon to be diagnosed with sideroblastic anemia(form of myelodysplastic syndrome)as a result from treatment for acute promyelocytic leukemia.This case report highlights the detection,treatment/maintenance with idarubicin,all-trans-retinoic-acid,arsenic trioxide,methotrexate,6-mercaptopurine,and ommaya reservoir intrathecal methotrexate administration in a patient that had central nervous system relapse of acute promyelocytic leukemia and acquired sideroblastic anemia.CONCLUSION In essence,first time relapse concerning the central nervous system in treated acute promyelocytic leukemia patients who had a good response to therapy is very uncommon.The acquirement of a myelodysplastic syndrome such as ringed sideroblastic anemia is also rare regarding this patient population.Although such cases are infrequent,this case report represents a unique insight of the detection,treatment,and maintenance of a 60-year-old man diagnosed with acute promyelocytic leukemia,resulting in the acquirement of sideroblastic anemia and central nervous system relapse.

Secondary acute promyelocytic leukemia following chemotherapy for gastric cancer: A case report

Therapy-related acute myeloid leukemia(t-AML) refers to a heterogeneous group of myeloid neoplasms that develop in patients following extensive exposure to either cytotoxic agents or radiation.The development of t-AML has been reported following treatment of cancers ranging from hematological malignancies to solid tumors; however, to our knowledge, t-AML has never been reported following treatment of gastric cancer.In this study, we report the development of t-acute promyelocytic leukemia in a cT 4N1M0 gastric cancer patient after an approximate 44 mo latency period following treatment with 4 cycles of oxaliplatin(OXP)(85 mg/m2 on day 1) plus capecitabine(1250 mg/m2 orally twice daily on days 1-14) in combination with recombinant human granulocyte-colony stimulating factor treatment.Karyotype analysis of the patient revealed 46,XY,t(15;17)(q22;q21)[15]/46,idem,-9,+add(9)(p22)[2]/46,XY[3], which, according to previous studies, includes some "favorable" genetic abnormalities.The patient was then treated with all-trans retinoic acid(ATRA, 25 mg/m2/d) plus arsenic trioxide(ATO, 10 mg/d) and attained complete remission.Our case illuminated the role of certain cytotoxic agents in the induction of t-AML following gastric cancer treatment.We recommend instituting a mandatory additional evaluation for patients undergoing these therapies in the future.

Sweet syndrome and differentiation syndrome in a patient with acute promyelocytic leukemia

The differentiation syndrome is an inflammatory reaction with increased capillary permeability that occurs in up to 25% of patients with acute promyelocytic leukemia treated with all-trans retinoic acid. A 50-year-old man with acute promyelocytic leukemia underwent chemotherapy with idarubicin and all-trans retinoic acid. On day +21 the patient developed pruritic prepatelar papules as well as several 10 mm subcutaneous nodules in both thighs accompanied by persistent fever. On the day +25 the patient presented with bilateral pulmonary crackles, infiltrates in the right lower lobe and severe hypotension which required dopamine infusion. Biopsy of one of the thighs nodules was performed. A Sweet syndrome associated to a differentiation syndrome was suspected. All-trans retinoic acid therapy was discontinued and dexamethasone was administered. In 48 h the patient showed remission of the fever and the infiltrates and the skin lesions acquired a residual aspect. It is debatable whether these two syndromes are distinct entities with common mechanisms or whether they are poles of the same spectrum. Dermatologists and hematologists must be aware of these two syndromes and its pathophysiologic association.

Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.