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BACKGROUND AND AIMS: Liver involvement portends poor prognosis in adults. We aimed to characterize the clinical features, liver function tests, radiologic findings, molecular profiles, therapeutic approaches and outcomes of adults patients with Langerhans cell histiocytosis (LCH) with liver involvement. METHODS: We conducted a retrospective analysis of all adults with LCH (≥â 18 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022. RESULTS: Among the 445 newly diagnosed adults with LCH, 90 patients had liver involvement at diagnosis and 22 patients at relapse. The median age was 32 years (range, 18-66 years). Of 112 evaluable patients, 108 had full liver function testing, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and total bilirubin and albumin. Elevated ALP was seen in 63.0% and GGT in 86.1%; 14.8% had elevated bilirubin. Next-generation sequencing of 54 patients revealed frequent BRAFN486_P490 (29.6%), BRAFV600E (18.5%), and MAP2K1 (14.8%). OUTCOMES: After a median 40 months' follow-up (range 1-168 months), 3-year progression-free survival (PFS) and overall survival were 49.7% and 86.6% respectively. In multivariable analyses, ≥3 abnormal liver function tests (HR 3.384, 95% CI 1.550-7.388, Pâ =â .002) associated with inferior PFS; immunomodulatory drug therapy (HR 0.073, 95% CI, 0.010-0.541, Pâ =â .010) correlated with superior PFS versus chemotherapy. CONCLUSIONS: In summary, elevated GGT and ALP were common in adults with LCH liver involvement. Greater than equal to 3 abnormal liver function tests predicted poor outcomes. Immunomodulatory drug therapy was associated with favorable progression-free survival compared to chemotherapy.
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[This corrects the article DOI: 10.1016/j.ekir.2022.09.030.].
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BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare highly heterogeneous histiocytosis, which can be divided into single system and multiple system disease according to site of involvement. There is a paucity of studies examining unifocal LCH in adults in the molecular era. RESULTS: We retrospectively analysed records from 70 patients with unifocal LCH. The median age at diagnosis was 36 years (18-69). The most common organ involved was the bone (70.0%), followed by pituitary gland (7.1%). Target gene sequencing of lesion tissues was performed on 32 of the 70 patients. MAPK/PI3K pathway alterations were observed in 78.1% of the patients; the most common mutations included BRAFV600E (28.1%), MAP2K1 (18.8%) and PIK3CA (9.4%). After a median follow-up time of 39.4 months (0.7-211.8), 10 (14.3%) patients developed disease progression, of whom 4 had local recurrence, 2 progressed to single-system multifocal and 4 progressed to multiple system LCH. The 3-year progression-free survival (PFS) was 81.9%. Univariate analysis showed that age < 30 years at diagnosis was associated with worse 3-year PFS (52.2% vs. 97.0%, p = 0.005). The 3-year overall survival was 100%. CONCLUSIONS: In our large cohort of adults with unifocal LCH, we found that prognosis of unifocal LCH in adults was very good, and age < 30 years at diagnosis was associated with increased relapse risk.
Subject(s)
Histiocytosis, Langerhans-Cell , Phosphatidylinositol 3-Kinases , Humans , Adult , Adolescent , Young Adult , Middle Aged , Aged , Retrospective Studies , Histiocytosis, Langerhans-Cell/genetics , Disease Progression , GenomicsABSTRACT
Background: Multiple trials have confirmed that romiplostim could increase platelet count in individuals with primary immune thrombocytopenia (ITP), but no related study has assessed Chinese patients. Objectives: To assess the effectiveness of romiplostim as a second-line treatment of persistent or chronic ITP in Chinese adults. Methods: This phase III multicenter, randomized, placebo-controlled, double-blind, then open-label clinical trial (NCT02868099, CTR20150395) was conducted at 28 investigational sites in China. The patients were randomly assigned (3:1) to romiplostim (starting and maximum doses of 1 and 10 µg/kg, respectively) or placebo for 9 weeks (double-blind period), followed by the open-label period (both groups administered romiplostim) to week 22. The primary endpoint was the time (in weeks) during which platelet counts were ≥50 × 109/L in the double-blind period. Results: In this study, 202 patients (romiplostim, n = 151; placebo, n = 51) started the treatment. The median (range) numbers of weeks with platelet response after 6 weeks of treatment were 2 (0-6) and 0 (0-2) in patients administered romiplostim and placebo, respectively (P < .001). During the double-blind period, the proportions of patients with treatment-emergent adverse events were comparable between the romiplostim and placebo groups (82.8% vs 82.4%). The treatment-emergent adverse event with ≥10% difference in incidence between these 2 groups was injection site bleeding (1.3% vs 11.8%). Conclusion: Romiplostim significantly increased the time with maintained platelet response in patients with persistent or chronic ITP in comparison with placebo. No new safety signal was observed. Trial registration: ClinicalTrials.gov, NCT02868099. www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml, CTR20150395.
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Introduction: Currently, no consensus on optimal renal replacement modality has been reached for end-stage renal disease (ESRD) patients complicated with hemophilia. They may require infusion of coagulation factors during each hemodialysis session. In comparison, peritoneal dialysis (PD) might be preferred considering that coagulation replacement is only required for catheter placement. However, limited data on the safety and efficacy of PD for treating ESRD patients with hemophilia were reported. Methods: This is a single-center retrospective cohort study. ESRD patients diagnosed with hemophilia under PD in Peking Union Medical College Hospital from January 1, 1996 to December 31, 2021 were included and followed-up with every month. Their baseline clinical data, catheter insertion procedure, coagulation factor replacement, complications, and outcome were analyzed and compared with general PD patients. Results: In total, 8 patients diagnosed with hemophilia were included, all-male, with a mean age of 50.3±13.3 years old. Two were acquired hemophilia A, whereas the rest were hereditary hemophilia A (HHA). Seven patients experienced significant hemoglobin (Hgb) increment after PD. Peritoneal hemorrhage only consisted of a small portion of all hemorrhage. Patients with hemophilia seemed to have lower small solute clearance despite higher baseline peritoneal permeability, and appeared to have increased peritonitis rate than other male PD patients, yet this study is not powered to prove this. Conclusion: PD is a safe and effective choice for patients with hemophilia and ESRD requiring dialysis. More studies are required to evaluate this certain rare group of patients.
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Background: D-dimer (DD) has been indicated as a potential indicator due to its connection with the prognosis of the COVID-19 pandemic. Aging is linked to elevated DD levels in coagulation activation. However, few studies have investigated the correlation of DD with prognosis, especially in the old population. Therefore, this study aims at investigating the correlation of DD with prognosis in shock and perioperative populations over 65 years of age. Methods: We analyzed 9261 old patients admitted to intensive care units (ICUs) with either confirmed shock or in perioperative period of high-risk surgery, with 8813 of them had DD levels determined on admission. In-hospital mortality, length of ICU stay and ventilation time (VT) associated variables were assessed using generalized linear models. Results: Although DD levels had no positive correlations with in-hospital mortality (RR, 1.006; 95% CI, 0.998-1.014) and length of ICU stay (RR, 1.012; 95% CI, 0.997-1.028) in Model 3, they were strongly correlated with VT (RR, 1.577; 95% CI, 1.024-2.064). Higher DD levels in females (RR, 1.804; 95% CI, 1.116-2.602), those who used antibiotics (RR, 1.736; 95% CI, 1.092-2.453), those with surgery (RR, 1.640; 95% CI, 1.273-2.114), and those with shock (RR, 1.740; 95% CI, 1.001-2.687) had stronger correlation with longer VT than the counterparts. While patients who were between 65 and 74 years old (RR, 1.023; 95% CI, 1.003-1.043), with no use of antibiotics (RR, 1.007; 95% CI, 1.001-1.013) nor shock (RR, 1.011; 95% CI, 1.002-1.021), but had undergone surgical procedures (RR, 1.030; 95% CI, 1.012-1.048) were correlated with a longer ICU length of stay. Conclusion: DD levels at ICU admission are highly related to increased VT and length of ICU stay in the old population with either confirmed shock or after high-risk surgery, indicating the strong potential of DD as a marker with prognostic utility for all ICU patients in the future.
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COVID-19 , Shock , Aged , Anti-Bacterial Agents , Female , Fibrin Fibrinogen Degradation Products , Humans , Intensive Care Units , Length of Stay , Pandemics , Retrospective StudiesABSTRACT
BACKGROUND: Langerhans cell histiocytosis (LCH) is a myeloid dendritic cell disorder frequently affecting children more than adults. The presentation of LCH varies with age, however, the clinical characteristics and genetic profiles of adolescent LCH remain elusive. To address the knowledge gap, we performed a single-centre retrospective study of 36 adolescent LCH patients aged between 14 and 17 years at Peking Union Medical College Hospital. RESULTS: At the time of diagnosis, 10 patients were classified as unifocal single system LCH (27.8%), 2 patients had pulmonary single system LCH (5.6%), 5 patients had multifocal single system LCH with bone involvement (13.9%), and 19 patients had multisystem LCH (52.8%). The most prevalent involvement in multisystem patients was the pituitary gland (78.9%), followed by the bone (42.1%), lung (42.1%), and lymph nodes (42.1%). Eight (42.1%) patients had risk organ involvement. BRAFN486_P490 was detected in 50% of patients who underwent next generation sequencing, and BRAFV600E was detected in one patient. Chemotherapies were the first line treatment in 24 patients. One patient died and thirteen patients relapsed during the follow-up. The estimated 5-year OS rate and EFS rate were 94.7% and 59.0%, respectively. CONCLUSIONS: In this study, we report a large series of adolescent LCH patients. The clinical characteristics of adolescent LCH patients may be close to adult LCH. Compared with pediatric cases, adolescent LCH tends to have more pituitary lesions and pulmonary involvement, fewer skin and hematopoietic involvement, a higher frequency of BRAF deletion mutation, and a lower frequency of BRAFV600E mutation.
Subject(s)
Histiocytosis, Langerhans-Cell , Proto-Oncogene Proteins B-raf , Adolescent , Adult , Child , Histiocytosis, Langerhans-Cell/diagnosis , Humans , Lymph Nodes , Mutation , Proto-Oncogene Proteins B-raf/genetics , Retrospective StudiesABSTRACT
The present study aims to evaluate the characteristics and treatment outcomes of adult Langerhans cell histiocytosis (LCH) patients with thyroid involvement. We retrospectively described the clinical, biological, and genomic characteristics of a series of 36 LCH patients with thyroid involvement in our center between January 2001 and December 2021. At the time of diagnosis, only one patient was classified as having single-system LCH, and 35 patients were classified as having multisystem (MS) LCH. Three patients had coexisting papillary thyroid carcinoma. Patients with thyroid gland involvement had higher frequencies of pituitary (88.6% vs. 53.4%, P < 0.001), liver (45.7% vs. 20.7%, P = 0.003), and lymph node (54.3% vs. 31.6%, P = 0.012) involvement and a lower frequency of bone (45.7% vs. 72.0%, P = 0.003) involvement than patients without thyroid gland involvement. Sixteen patients had abnormal thyroid function, including nine patients with primary hypothyroidism, one patient with central hypothyroidism, and six patients with subclinical hypothyroidism. BRAFV600E, BRAF N486_P490, and MAP2K1 mutations were detected in 14.3%, 57.1%, and 7.1% of patients, respectively. After a 43-month median follow-up, none of the patients died, and 15 patients experienced reactivation. The median event-free survival was 37.5 months. Two of 6 patients with subclinical hypothyroidism had normal thyroid function, and 12 patients still had hypothyroidism after treatment. As the largest adult LCH cohort with thyroid gland involvement to date, we found that patients with thyroid gland involvement had different clinical characteristics, genetic profiles, and outcomes than patients without thyroid gland involvement.
Subject(s)
Histiocytosis, Langerhans-Cell , Hypothyroidism , Adult , Genomics , Histiocytosis, Langerhans-Cell/drug therapy , Histiocytosis, Langerhans-Cell/genetics , Humans , Proto-Oncogene Proteins B-raf/genetics , Retrospective StudiesABSTRACT
BACKGROUND: Non-Langerhans cell histiocytosis, including Erdheim-Chester disease (ECD), Rosai-Dorfman disease (RDD), indeterminate cell histiocytosis (ICH), and unclassified histiocytosis, is a rare disorder lacking a standard treatment strategy. We report our experience using intermediate-dose cytarabine as the first or subsequent therapy in non-Langerhans cell histiocytosis. RESULTS: Nine ECD patients, 5 RDD patients, 1 ICH patient and 1 unclassified histiocytosis patient were enrolled. Intermediate-dose cytarabine therapy was administered as 0.5-1.0 g/m2 of intravenous cytarabine every 12 h for 3 days every 5 weeks. The median age at cytarabine initiation was 47.5 years (range 18-70 years). The median number of cycles of cytarabine administered was 5.5 (range 2-6). The overall response rate (ORR) was 87.5% in the overall cohort, including 12.5% with complete response and 75.0% with partial response. One patient experienced disease recurrence 19 months after cytarabine therapy. The median follow-up duration for the entire cohort was 15.5 months (range 6-68 months). The estimated 2-year progression-free survival and overall survival rates were 85.6% and 92.3%, respectively. The most common toxicity was haematological adverse events, including grade 4 neutropenia and grade 3-4 thrombocytopenia. No treatment-related deaths occurred. CONCLUSIONS: Intermediate-dose cytarabine is an efficient treatment option for non-Langerhans cell histiocytosis patients, especially for those with CNS involvement.
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Erdheim-Chester Disease , Histiocytosis, Langerhans-Cell , Histiocytosis, Sinus , Neutropenia , Cytarabine/therapeutic use , Erdheim-Chester Disease/drug therapy , Histiocytosis, Langerhans-Cell/drug therapy , Histiocytosis, Sinus/drug therapy , HumansABSTRACT
Idarubicin 12 mg/m2 has been recommended as a standard induction therapy for acute myeloid leukemia (AML). It is unknown whether a higher dose of idarubicin can improve the remission rate. This phase 2 prospective single-arm study enrolled 45 adults with newly diagnosed AML between September 2019 and May 2021 (NCT 04,069,208). Induction therapy included administration of idarubicin 14 mg/m2 for 3 days and cytarabine 100 mg/m2 every 12 h subcutaneously for 7 days. The primary endpoint was the composite complete response rate (complete response (CR) plus complete response with incomplete blood count recovery (CRi)). The median age was 45 years (range 14-60 years). Forty (88.9%) patients had CR or CRi, including 39 patients with CR and 1 patient with CRi after one course of induction therapy. The median times to recovery of absolute neutrophil and platelet counts were 21 days. Only 1 patient died of intracranial hemorrhage during induction therapy. After a median follow-up of 14 months (range 3.5-24 months), the estimated 18-month overall survival and disease-free survival (DFS) were 66.9% and 57.5%, respectively. In conclusion, idarubicin 14 mg/m2 plus cytarabine was a safe and efficient intensive regimen for younger and fit patients with newly diagnosed AML.
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Idarubicin , Leukemia, Myeloid, Acute , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cytarabine , Humans , Induction Chemotherapy , Leukemia, Myeloid, Acute/drug therapy , Middle Aged , Prospective Studies , Remission Induction , Young AdultABSTRACT
Adult Langerhans cell histiocytosis (LCH) remains poorly defined. We retrospectively studied 266 newly diagnosed LCH patients to understand the clinical presentation, treatment, and prognosis of adult LCH. The median age at diagnosis was 32 years (range, 18-79 years). At the time of diagnosis, 40 patients had single lesions within a single system, 18 patients had single pulmonary LCH, 26 patients had multiple lesions within a single system (SS-m), and 182 patients had multisystem disease (MS). The most common organ involved in MS patients was the bone (69.8%), followed by the pituitary (61.5%) and lung (61.0%). BRAFV600E , BRAF deletion, and MAP2K1 mutation were detected in 38.8%, 25.4%, and 19.4% patients, respectively. BRAF deletion was found more common in patients with MS LCH compared to single-system LCH (38.5% vs 7.1%, p = .004), also in patients with liver involvement (69.2% vs 14.3%, p < .001). The estimated 3-year overall survival (OS) and event-free survival (EFS) rates were 94.4% and 54.7%, respectively, in SS-m and MS LCH. Multivariate Cox regression showed that involvement of the liver or spleen at baseline predicted poor EFS and receiving cytarabine-based therapy as a first-line treatment and age older than 30 years at diagnosis predicted favorable EFS. The involvement of risk organs and age older than 50 years predicted poor OS, and receiving cytarabine-based therapy predicted favorable OS. Therefore, BRAF deletion was correlated with MS LCH, particularly those with liver involvement. Liver or spleen involvement at baseline indicates a poor prognosis, and a cytarabine-based regimen could be considered as first-line treatment for adult LCH patients.
Subject(s)
Histiocytosis, Langerhans-Cell/diagnosis , Adult , Aged , Cytarabine/therapeutic use , Female , Histiocytosis, Langerhans-Cell/genetics , Histiocytosis, Langerhans-Cell/therapy , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
OBJECTIVES: To illuminate the prognostic value of ADC (apparent diffusion coefficient), an important quantitative parameter of diffusion-weighted MRI, for multiple myeloma (MM). METHODS: A prospective single-center study which enrolled 114 consecutive newly diagnosed MM patients with baseline whole-body diffusion-weighted MRI (WB DW-MRI) results was conducted. Baseline clinical and MRI parameters were analyzed with univariate and multivariate approaches to identify independent risk factors for progression-free survival (PFS) and overall survival (OS). RESULTS: Five different DW-MRI patterns were seen, and the mean ADC value of the representative background bone marrow was 0.4662 ± 0.1939 × 10-3 mm2/s. After a mean follow-up of 50.2 months (range, 15.7-75.8 months), twenty-four patients died and seven were lost to follow-up. The mean ADC value of the representative background bone marrow was showed to be an independent risk factor for both PFS (HR 4.664; 95% confidence interval (CI) 1.138-19.121; p = 0.032) and OS (HR 14.130; 95% CI 1.544-129.299; p = 0.019). Normal/salt-and-pepper pattern on DW-MRI was associated with PFS using univariate analysis (p = 0.035) but lost the significance with multivariate Cox regression. CONCLUSIONS: Mean ADC value of the representative background bone marrow predicts both PFS and OS which suggests the role of baseline DW-MRI for risk stratification in newly diagnosed MM patients. KEY POINTS: ⢠Whole-body diffusion-weighted MRI (WB DW-MRI) might be helpful to improve the current risk stratification systems for newly diagnosed multiple myeloma (MM). ⢠Morphological parameters as MRI pattern and focal lesion-associated parameters have been reported to be related to survival. However, important functional parameters such as apparent diffusion coefficient (ADC) values were not incorporated into the current risk stratification model. ⢠This study is one of the first endeavors to delineate the correlation of baseline ADC values and survival in MM patients. It is revealed that the mean ADC value of the representative background bone marrow (L3-S1 and iliac bone) was an independent risk factor for both PFS and OS.
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Diffusion Magnetic Resonance Imaging , Multiple Myeloma , Bone Marrow/diagnostic imaging , Humans , Multiple Myeloma/diagnostic imaging , Prospective Studies , Whole Body ImagingSubject(s)
Cytarabine/administration & dosage , Histiocytosis, Langerhans-Cell , Methotrexate/administration & dosage , Adolescent , Adult , Aged , Cytarabine/adverse effects , Disease-Free Survival , Drug Therapy, Combination , Female , Histiocytosis, Langerhans-Cell/diagnosis , Histiocytosis, Langerhans-Cell/drug therapy , Histiocytosis, Langerhans-Cell/mortality , Humans , Male , Methotrexate/adverse effects , Middle Aged , Prospective Studies , Survival RateABSTRACT
Extranodal natural killer/T cell lymphoma, nasal type (ENKL) is a highly aggressive tumor with relatively poor prognosis. In this prospective study, we investigated the efficacy and toxicity of a novel GDP-ML regimen (combined gemcitabine, cisplatin, dexamethasone, methotrexate, and pegaspargase) as front-line treatment in newly diagnosed ENKL. Eligible newly diagnosed stage I/II ENKL patients received sandwich chemoradiation therapy. Patients with stage III/IV disease received an initial 4 cycles of GDP-ML regimen. After 4 cycles, responding patients continued to receive either autologous transplantation or additional two courses of GDP-ML. A total of 44 patients were enrolled with a median follow-up of 26 months. The overall response rate (ORR) were 78.6% for the whole cohort, 84.6% for stage I/II, and 66.7% for stage III/IV, and corresponding complete remission (CR) rates were 61.9%, 76.9%, and 33.3%. The 1- year and 2- year progression-free survival (PFS) rates were 69.3% and 62.9%, and 1- year and 2-year overall survival (OS) rates were 76.5% and 67.4%, respectively. Patients with stage I/II disease showed better 2-year OS rate compared with stage III/IV patients (88.1% vs. 33.2%, p < 0.001). Patients who achieved CR had significantly better 2-year OS rate compared with non-CR patients (90.8% vs. 24.5%, p < 0.001). The main adverse event was hematologic toxicity. Grade 3/4 neutropenia occurred in 59.1% of patients. These results indicate that GDP-ML is an effective and well-tolerated induction regimen with newly diagnosed ENKL patients. This clinical trial was registered on www.chictr.org.cn (ChiCTR-ONC-12002055).
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Asparaginase/administration & dosage , Cisplatin/administration & dosage , Deoxycytidine/analogs & derivatives , Lymphoma, Extranodal NK-T-Cell/drug therapy , Methotrexate/administration & dosage , Nose Neoplasms/drug therapy , Polyethylene Glycols/administration & dosage , Adult , Aged , Deoxycytidine/administration & dosage , Female , Follow-Up Studies , Humans , Lymphoma, Extranodal NK-T-Cell/diagnostic imaging , Lymphoma, Extranodal NK-T-Cell/mortality , Male , Middle Aged , Nose Neoplasms/diagnostic imaging , Nose Neoplasms/mortality , Prospective Studies , Survival Rate/trends , Young Adult , GemcitabineSubject(s)
Anemia, Hemolytic, Autoimmune/drug therapy , Bortezomib/administration & dosage , Rituximab/administration & dosage , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/immunology , Drug Resistance , Drug Therapy, Combination , Humans , Molecular Targeted Therapy , Retreatment , Treatment OutcomeSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System/pathology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cerebrospinal Fluid/cytology , Chemical and Drug Induced Liver Injury/etiology , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Kaplan-Meier Estimate , Kidney Diseases/chemically induced , Leucovorin/administration & dosage , Lymphoma, Large B-Cell, Diffuse/cerebrospinal fluid , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Methotrexate/administration & dosage , Methotrexate/adverse effects , Middle Aged , Mucositis/chemically induced , Neoplasm Invasiveness , Prednisone/administration & dosage , Proportional Hazards Models , Prospective Studies , Recurrence , Rituximab/administration & dosage , Vincristine/administration & dosageABSTRACT
Peripheral T cell lymphomas (PTCL) are less responsive to anthracycline-containing regimen such as CHOP and carry a poor prognosis. In this prospective study, we investigated gemcitabine, cisplatin, and dexamethasone (GDP) combined with methotrexate (MTX) and pegaspargase (PEG-L) as front-line treatment in PTCL. Eligible newly diagnosed PTCL patients received 4 cycles of the GDP-ML chemotherapy every 28 days. After 4 cycles, responding patients continued to receive either autologous stem cell transplantation or the MTX/cytarabine (MA) regimen for consolidation. This trial is registered with www.chictr.org.cn (ChiCTR-ONC-12002055). A total of 65 patients were enrolled with a median follow-up of 38.5 months. The overall response rate (ORR) was 55.4%, and complete remission rate (CR) was 33.8%. The median overall survival (OS) was 16 months, and the 1-year and 2-year OS were 59.1% and 38.2%, respectively. The median PFS was only 8 months. The main adverse event was hematologic toxicity: 50% patients showed grade III/IV neutropenia. GDP-ML for the first-line treatment of PTCL patients is an effective induction regimen compared with standard CHOP, and the toxicity was more significant but acceptable. However, future studies exploring new drug combinations are warranted to overcome relapse after remission. ClinicalTrials.gov Identifier: NCT02987244.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Lymphoma, T-Cell, Peripheral/drug therapy , Lymphoma, T-Cell, Peripheral/mortality , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Asparaginase/administration & dosage , Asparaginase/adverse effects , China/epidemiology , Cisplatin/administration & dosage , Cisplatin/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Disease-Free Survival , Female , Follow-Up Studies , Humans , Lymphoma, T-Cell, Peripheral/pathology , Male , Methotrexate/administration & dosage , Methotrexate/adverse effects , Middle Aged , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Survival Rate , GemcitabineABSTRACT
The incidence and clinical implications of autoimmune diseases (ADs) in patients with non-Hodgkin's lymphoma(NHL) remain unclear. The aim of this study was to examine the prevalence of ADs in NHL and define the clinical characteristics and prognosis of AD-associated NHL patients. Patients diagnosed with NHL in our institute between 1995 and 2017 were retrospectively reviewed to assess the incidence of ADs. Of 4880 patients with NHL, 140 (2.9%) presented with autoimmunity, with a total of 24 ADs. The most common AD was Sjögren syndrome, followed by autoimmune cytopenia, psoriasis, rheumatoid arthritis, etc. Psoriasis and rheumatoid arthritis were significantly associated with pre-existing ADs, whereas autoimmune cytopenia was significantly associated with secondary AD. Sjögren syndrome was significantly associated with B-cell lymphoma, and systemic vasculitis was significantly associated with T-cell lymphoma. Patients with AD-associated NHL had a high frequency of extranodal involvement(87%), with significant associations between specific extranodal sites of lymphoma and subtypes of ADs. Among patients with available data on pre-treatment peripheral blood Epstein-Barr virus (EBV) DNA(n = 68), elevated EBV-DNA load was observed in a variety of NHL subtypes, including 20% of marginal zone lymphoma and 14.3% of follicular lymphoma patients. In a matched-pair analysis, survival did not differ significantly between NHL patients with and without ADs. However, for NHL patients with pre-existing ADs, a prior history of systemic corticosteroids therapy was significantly associated with worse survival (HR = 7.33, P = 0.006). Taken together, our data suggest that a broad spectrum of ADs is associated with NHL, and AD-associated NHL has distinct features with regard to clinical manifestations and prognosis.
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Autoimmune Diseases/mortality , Lymphoma, B-Cell, Marginal Zone/mortality , Lymphoma, Follicular/mortality , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adult , Aged , Aged, 80 and over , Autoimmune Diseases/drug therapy , China/epidemiology , Disease-Free Survival , Female , Humans , Lymphoma, B-Cell, Marginal Zone/drug therapy , Lymphoma, Follicular/drug therapy , Male , Middle Aged , Retrospective Studies , Survival RateABSTRACT
INTRODUCTION: Lenalidomide is an effective therapy of POEMS syndrome. However, there is concern that exposure to lenalidomide may reduce the efficiency of blood cell collection in persons who may eventually receive an autotransplant. We studied the impact of lenalidomide therapy on subsequent blood cell mobilization and collection including frequency of blood CD34+ cells and CXCR4 expression before and after mobilization with cyclophosphamide and granulocyte-colony stimulating factor (G-CSF). MATERIAL AND METHODS: Forty-three subjects with POEMS were assigned to receive lenalidomide and dexamethasone for 2-4 28 d cycles (n = 19) or no therapy (n = 24). All subjects then received cyclophosphamide and G-CSF. Neither cohort had substantial numbers of blood CD34+ cells before mobilization. RESULTS: Mobilization increased blood CD34+ frequency in lenalidomide-treated subjects and controls similarly (0.25% (95% confidence interval (CI): 0.03-1.39% vs. 0.32%, 0.04-1.47%), p = 0.472). Increases in blood CD34+ numbers were also similar (10 × 106/l) (5-77 × 106/l) vs. 14 × 106/l (6-101 × 106/l), p = 0.312). Mean CXCR4 fluorescence intensity on bone marrow cells from controls decreased from 58 ±34 (mean ± SD) to 31 ±16 after mobilization (p = NS). In contrast, mean CXCR4 intensity on bone marrow cells in lenalidomide-treated subjects increased from 55 ±43 to 89 ±40 (p = 0.017, comparing the deviation between two groups). Median numbers of CD34+ cells collected in lenalidomide-treated subjects and controls were 2.3 × 106/kg (0.6-6.8 × 106/kg) and 2.8106/kg (1.0-8.9 × 106/kg; p = 0.521). CONCLUSIONS: Brief lenalidomide treatment for POEMS did not reduce numbers of CD34+ blood cells collected but increased CXCR4 expression on bone marrow CD34+ cells.