Large granular lymphocytic leukemia(LGLL)is characterized by the clonal proliferation of cytotoxic T lymphocytes or NK cells.Standard first-line immunosuppressive treatments have limitations,achieving complete remissi...Large granular lymphocytic leukemia(LGLL)is characterized by the clonal proliferation of cytotoxic T lymphocytes or NK cells.Standard first-line immunosuppressive treatments have limitations,achieving complete remission(CR)rates of up to 50%.Immune system dysregulation is implicated in LGLL.Promising results for thalidomide,an immunomodulatory drug,combined with prednisone and methotrexate(TPM),were observed in our pilot study.This multicenter study evaluated the effcacy and safety of a thalidomide,prednisone,and methotrexate(TPM)regimen in 52 symptomatic,methotrexate-and thalidomide-naive LGLL patients from June 2020 to August 2022.Thalidomide(100 mg daily for up to 24 months),prednisone(0.5-1.0 mg/kg every other day,tapered after 3 months),and methotrexate(10 mg/m^(2) weekly for up to 12 months)were administered.The primary objective was to determine the CR rate.The median follow-up duration was 29.0 months(range:4.0-42.0).Forty-seven patients(90.4%)achieved hematological and symptomatic responses.Thirty-nine patients(75.0%)achieved CR.The median time to response was 3.0 months(range:3.0-9.0).The median progression-free survival was 40.0 months(95%confidence interval(Cl):38.0-42.0),and the median duration of response was 39.0 months(95%Cl:36.1-41.9).The most common adverse event was peripheral neuropathy(24.1%),most of which(84.6%)were grades 1-2.Four patients experienced grade≥3 adverse events.In conclusion,the TPM regimen was an effective and safe treatment for symptomatic LGLL patients,with a particularly high CR rate.This trial was registered at www.clinicaltrials.gov(#NCT04453345).展开更多
To the Editor:Multiple myeloma(MM)is a plasma cell disorder characterized by heterogeneous features.^([1])Accurate risk stratification could predict diverse prognoses of patients with myeloma and attain risk-adapted t...To the Editor:Multiple myeloma(MM)is a plasma cell disorder characterized by heterogeneous features.^([1])Accurate risk stratification could predict diverse prognoses of patients with myeloma and attain risk-adapted therapy to extend their lifespan.Recently,the European Myeloma Network(EMN)conducted a large retrospective analysis involving more than 7000 patients with myeloma and developed a new risk model defined as the Second Revision of International Staging System(R2-ISS),with excellent risk distribution among patients enrolled in clinical trials.^([2])The R2-ISS stratifications were based on weighted risk scores of different prognostic factors:ISS II 1.0 point,ISS III 1.5 points,del(17p)1.0 point,elevated lactate dehydrogenase(LDH)1.0 point,t(4;14)1.0 point,and 1q21+0.5 points.展开更多
Rituximab maintenance(RM)prolongs the progression-free survival(PFS)of responding patients with follicular lymphoma(FL),but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index(FLIP...Rituximab maintenance(RM)prolongs the progression-free survival(PFS)of responding patients with follicular lymphoma(FL),but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index(FLIPI)risk group is still confusing.We performed a retrospective analysis of the effect of RM treatments in patients with FL responding to induction therapy based on their FLIPI risk assessment carried out prior to treatment.We identified 93 patients between 2013 and 2019 who received RM every 3 months for≥4 doses(RM group),and 60 patients who did not accept RM or received rituximab less than 4 doses(control group).After a median follow-up of 39 months,neither median overall survival(OS)nor PFS was reached for the entire population.The PFS was significantly prolonged in the RM group compared to the control group(median PFS NA vs 83.1 months,P=.00027).When the population was divided into the 3 FLIPI risk groups,the PFS differed significantly(4-year PFS rates,97.5%vs 88.8%vs 72.3%,P=.01)according to group.There was no significant difference in PFS for FLIPI low-risk patients with RM compared to the control group(4-year PFS rates,100%vs 93.8%,P=.23).However,the PFS of the RM group was significantly prolonged for FLIPI intermediate-risk(4-year PFS rates,100%vs 70.3%,P=.00077)and high-risk patients(4-year PFS rates,86.7%vs 57.1%,P=.023).These data suggest that standard RM significantly prolongs the PFS of patients assigned to intermediate-and high-risk FLIPI groups but not to low-risk FLIPI group,and pending larger-scale studies to validate.展开更多
To the Editor:As a rare indolent B cell non-Hodgkin lymphoma,lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia(LPL/WM)has unique clinical and biological characteristics.[1]However,due to the difficulties in...To the Editor:As a rare indolent B cell non-Hodgkin lymphoma,lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia(LPL/WM)has unique clinical and biological characteristics.[1]However,due to the difficulties in obtaining tumor metaphase for karyotyping and slow cell proliferation,only very few studies have detected the cytogenetic aberration of LPL/WM.[2,3]In addition,6q deletion is the most common cytogenetic aberration in WM,with an incidence rate of about 50%.[2]Nevertheless,other cytogenetic aberrations remain largely unclear,and the prognostic role of cytogenetic aberrations needs to be further explored.In the present study,we systematically analyzed 305 LPL/WM cases in China,focusing on the characteristics and cytogenetic aberrations in Chinese patients.展开更多
To the Editor:Diffuse large B-cell lymphoma(DLBCL)exhibits clinical significance and biological diversity.Over the last two decades,rituximab with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)has sub...To the Editor:Diffuse large B-cell lymphoma(DLBCL)exhibits clinical significance and biological diversity.Over the last two decades,rituximab with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)has substantially improved outcomes for DLBCL patients.However,approximately one-third of DLBCL cases continue to experience disease progression,resulting in long-term survival ranging from 50%to 60%.[1]Efforts to improve DLBCL patient outcomes by modifying R-CHOP dosing schedules have yielded limited success,and the addition of new drugs has benefited only specific patient subgroups.Nevertheless,intensive immunochemotherapy(IIC)has demonstrated promise and cost-effectiveness in recent years.The regimen of dose-adjusted etoposide.展开更多
Waldenstrom macroglobulinemia(WM)is a type of incurable,indolent B-cell lymphoma that is prone to relapse.Over time,treatment strategies have progressed from cytotoxic drugs to rituximab(R)-or bortezomib(V)-based regi...Waldenstrom macroglobulinemia(WM)is a type of incurable,indolent B-cell lymphoma that is prone to relapse.Over time,treatment strategies have progressed from cytotoxic drugs to rituximab(R)-or bortezomib(V)-based regimens,and have now entered into an era of Bruton tyrosine kinase inhibitor(BTKi)-based regimens.However,the optimal treatment for the relapsed patients is still unclear.Herein,we analyzed the outcomes of the first-and second-line therapies in 377 patients with WM to illustrate the optimal choices for second-line therapy.After a median follow-up of 45.4 months,89 patients received second-line therapy,and 53 patients were evaluated for response.The major response rates(MRR)of first-and second-line treatment were 65.1%and 67.9%(P=0.678).The median progression-free survival(PFS)for the second-line therapy(PFS2)was shorter than that for the first-line therapy(PFS1)(56.3 vs 40.7 months,P=0.03).However,PFS2 in targeted drugs group(R-/V-/BTKi-based regimens)was comparable to PFS1(60.7 months vs 44.7 months,respectively,P=0.21).Regarding second-line therapy,patients who underwent sequential treatment escalation—such as transitioning from cytotoxic drugs to R-/V-/BTKi-based regimens or from R-/V-based to BTKi-based regimens(escalation group)—had higher MRR(80.6%vs 47.1%,respectively,P=0.023)and longer PFS2(50.4 vs 23.5 months,respectively,P<0.001)compared to the non-escalation group.Patients in the escalation group also had longer post-relapse overall survival compared with the non-escalation group(median,not reached vs 50.7 months,respectively,P=0.039).Our findings indicate that sequential treatment escalation may improve the survival of patients with WM.展开更多
基金supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-12M-C&T-B-081 and 2022-I2M-1-022)the National Nature Science Foundation of China(82170193,82370197,82200215)+1 种基金the Tianjin Health Science and Technology Project(TJWJ2022XK021)the Tianjin Health Research Project(TJSQNYXXR-D2-152).
文摘Large granular lymphocytic leukemia(LGLL)is characterized by the clonal proliferation of cytotoxic T lymphocytes or NK cells.Standard first-line immunosuppressive treatments have limitations,achieving complete remission(CR)rates of up to 50%.Immune system dysregulation is implicated in LGLL.Promising results for thalidomide,an immunomodulatory drug,combined with prednisone and methotrexate(TPM),were observed in our pilot study.This multicenter study evaluated the effcacy and safety of a thalidomide,prednisone,and methotrexate(TPM)regimen in 52 symptomatic,methotrexate-and thalidomide-naive LGLL patients from June 2020 to August 2022.Thalidomide(100 mg daily for up to 24 months),prednisone(0.5-1.0 mg/kg every other day,tapered after 3 months),and methotrexate(10 mg/m^(2) weekly for up to 12 months)were administered.The primary objective was to determine the CR rate.The median follow-up duration was 29.0 months(range:4.0-42.0).Forty-seven patients(90.4%)achieved hematological and symptomatic responses.Thirty-nine patients(75.0%)achieved CR.The median time to response was 3.0 months(range:3.0-9.0).The median progression-free survival was 40.0 months(95%confidence interval(Cl):38.0-42.0),and the median duration of response was 39.0 months(95%Cl:36.1-41.9).The most common adverse event was peripheral neuropathy(24.1%),most of which(84.6%)were grades 1-2.Four patients experienced grade≥3 adverse events.In conclusion,the TPM regimen was an effective and safe treatment for symptomatic LGLL patients,with a particularly high CR rate.This trial was registered at www.clinicaltrials.gov(#NCT04453345).
基金supported by the National Natural Science Foundation of China(Nos.81920108006,82270218)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Nos.2021-I2M-1-041,2022-I2M-1-022).
文摘To the Editor:Multiple myeloma(MM)is a plasma cell disorder characterized by heterogeneous features.^([1])Accurate risk stratification could predict diverse prognoses of patients with myeloma and attain risk-adapted therapy to extend their lifespan.Recently,the European Myeloma Network(EMN)conducted a large retrospective analysis involving more than 7000 patients with myeloma and developed a new risk model defined as the Second Revision of International Staging System(R2-ISS),with excellent risk distribution among patients enrolled in clinical trials.^([2])The R2-ISS stratifications were based on weighted risk scores of different prognostic factors:ISS II 1.0 point,ISS III 1.5 points,del(17p)1.0 point,elevated lactate dehydrogenase(LDH)1.0 point,t(4;14)1.0 point,and 1q21+0.5 points.
基金the National Natural Science Foundation of China(81970187,82170193,81920108006,and 81900203)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-C&T-B-081).
文摘Rituximab maintenance(RM)prolongs the progression-free survival(PFS)of responding patients with follicular lymphoma(FL),but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index(FLIPI)risk group is still confusing.We performed a retrospective analysis of the effect of RM treatments in patients with FL responding to induction therapy based on their FLIPI risk assessment carried out prior to treatment.We identified 93 patients between 2013 and 2019 who received RM every 3 months for≥4 doses(RM group),and 60 patients who did not accept RM or received rituximab less than 4 doses(control group).After a median follow-up of 39 months,neither median overall survival(OS)nor PFS was reached for the entire population.The PFS was significantly prolonged in the RM group compared to the control group(median PFS NA vs 83.1 months,P=.00027).When the population was divided into the 3 FLIPI risk groups,the PFS differed significantly(4-year PFS rates,97.5%vs 88.8%vs 72.3%,P=.01)according to group.There was no significant difference in PFS for FLIPI low-risk patients with RM compared to the control group(4-year PFS rates,100%vs 93.8%,P=.23).However,the PFS of the RM group was significantly prolonged for FLIPI intermediate-risk(4-year PFS rates,100%vs 70.3%,P=.00077)and high-risk patients(4-year PFS rates,86.7%vs 57.1%,P=.023).These data suggest that standard RM significantly prolongs the PFS of patients assigned to intermediate-and high-risk FLIPI groups but not to low-risk FLIPI group,and pending larger-scale studies to validate.
基金National Nature Science Foundation of China(Nos.81900203,81970187,82170193,and 81920108006)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Nos.2022-12M-1-022,2021-I2M-C&T-B-081)
文摘To the Editor:As a rare indolent B cell non-Hodgkin lymphoma,lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia(LPL/WM)has unique clinical and biological characteristics.[1]However,due to the difficulties in obtaining tumor metaphase for karyotyping and slow cell proliferation,only very few studies have detected the cytogenetic aberration of LPL/WM.[2,3]In addition,6q deletion is the most common cytogenetic aberration in WM,with an incidence rate of about 50%.[2]Nevertheless,other cytogenetic aberrations remain largely unclear,and the prognostic role of cytogenetic aberrations needs to be further explored.In the present study,we systematically analyzed 305 LPL/WM cases in China,focusing on the characteristics and cytogenetic aberrations in Chinese patients.
基金CAMS Innovation Fund for Medical Sciences(Nos.CIFMS 2022-I2M-1-022 and 2020-I2M-C&T-B-085)
文摘To the Editor:Diffuse large B-cell lymphoma(DLBCL)exhibits clinical significance and biological diversity.Over the last two decades,rituximab with cyclophosphamide,doxorubicin,vincristine,and prednisone(R-CHOP)has substantially improved outcomes for DLBCL patients.However,approximately one-third of DLBCL cases continue to experience disease progression,resulting in long-term survival ranging from 50%to 60%.[1]Efforts to improve DLBCL patient outcomes by modifying R-CHOP dosing schedules have yielded limited success,and the addition of new drugs has benefited only specific patient subgroups.Nevertheless,intensive immunochemotherapy(IIC)has demonstrated promise and cost-effectiveness in recent years.The regimen of dose-adjusted etoposide.
基金supported by grants from the National Nature Science Foundation of China(81970187,82170193,81920108006,and 81900203)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2022-I2M-1-022,2021-I2M-C,and T-B-081).
文摘Waldenstrom macroglobulinemia(WM)is a type of incurable,indolent B-cell lymphoma that is prone to relapse.Over time,treatment strategies have progressed from cytotoxic drugs to rituximab(R)-or bortezomib(V)-based regimens,and have now entered into an era of Bruton tyrosine kinase inhibitor(BTKi)-based regimens.However,the optimal treatment for the relapsed patients is still unclear.Herein,we analyzed the outcomes of the first-and second-line therapies in 377 patients with WM to illustrate the optimal choices for second-line therapy.After a median follow-up of 45.4 months,89 patients received second-line therapy,and 53 patients were evaluated for response.The major response rates(MRR)of first-and second-line treatment were 65.1%and 67.9%(P=0.678).The median progression-free survival(PFS)for the second-line therapy(PFS2)was shorter than that for the first-line therapy(PFS1)(56.3 vs 40.7 months,P=0.03).However,PFS2 in targeted drugs group(R-/V-/BTKi-based regimens)was comparable to PFS1(60.7 months vs 44.7 months,respectively,P=0.21).Regarding second-line therapy,patients who underwent sequential treatment escalation—such as transitioning from cytotoxic drugs to R-/V-/BTKi-based regimens or from R-/V-based to BTKi-based regimens(escalation group)—had higher MRR(80.6%vs 47.1%,respectively,P=0.023)and longer PFS2(50.4 vs 23.5 months,respectively,P<0.001)compared to the non-escalation group.Patients in the escalation group also had longer post-relapse overall survival compared with the non-escalation group(median,not reached vs 50.7 months,respectively,P=0.039).Our findings indicate that sequential treatment escalation may improve the survival of patients with WM.
