Post Transplant Lymphoproliferative Disorders: Prognostic Features and Rituximab Impact In a 120 Case Single Institution Series

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4151-4151
Author(s):  
Francesca Montanari ◽  
Govind Bhagat ◽  
Venkatraman Seshan ◽  
Sean Clark-Garvey ◽  
Jasmine M. Zain ◽  
...  
Keyword(s):  
High Risk ◽  
Pediatric Patients ◽  
Nk Cell ◽  
Risk Group ◽  
Single Agent ◽  
High Risk Group ◽  
Lymphoproliferative Disorders ◽  
Adult Patients ◽  
Single Institution ◽  
Post Transplant

Abstract Abstract 4151 Post-transplant lymphoproliferative disorder (PTLD) is a broad spectrum of lymphoproliferative disorders that can occur after solid organ transplant or hematopoietic stem cell transplant. The incidence ranges from 1% to 20% depending on the type of organ graft, the intensity of the immunosuppression and the Epstein-Barr virus (EBV) serostatus. It represents a serious and potentially life threatening complication, with reported mortality rate up to 40–50%. According to the World Health Organization classification system, PTLD are classified as early lesions (EL), polymorphic (p-PTLD), monomorphic (m-PTLD), and Hodgkin-like (HL). Here we analyzed the prognosis and clinical characteristics of 120 patients diagnosed and treated over a 19-year period (from 1990 to 2009). To the best of our knowledge, this is the largest series of PTLD to be reported by a single Institution. The cases were classified as follows: 70 (58.3%) m-PTLD, 34 (28.3%) p-PTLD, 14 (11.7%) EL, and 2 (1.7%) HL. In the m-PTLD group, 59 were of B-cell origin (52 DLBCL, 4 BL, 2 plasmacytoma-like, 1 multiple myeloma and 1 pleural effusion) and 10 were of T/NK cell lineage (4 peripheral T-cell lymphomas, 2 CTCL, 2 HSTCL, 1 T-ALL and 1 NK-cell lymphoma). The age of the patients ranged from 1 to 76 years, with 39 pediatric patients (<16 year old) and 81 adult patients. The EBV status of the PTLD, was determined in 94 cases, 58 (61.7%) were positive and 38 (38.3%) were negative, with no difference between pediatric and adult patients (p=0.11). CD 20 positivity was available in 106 specimens and was highly expressed in our series (87.6%) with no differences between adult and pediatric patients (p=0.4). Approximately half of the patients were diagnosed in stage I or II of disease (44.2%), and the other half in advanced stage III or IV (55.8%) with no substantial differences between adults and pediatrics (p=1). ECOG score 0 or 1 was observed in 2/3 of the patients (67.2%), and it was more frequently observed in pediatrics than in adults (respectively 80% and 61%) but the difference was not statistically significant (p=0.06). Younger age, CD 20 positivity, good ECOG score, platelet and absolute neutrophil count within normal limits correlated with a longer OS (p=0.001, P<0.001, P<0.001, P<0.001 and p=0.003 respectively). PTLD subtype (i.e. EL, pPTLD, mPTLD, HL), gender, decade of diagnosis (1990-1999 vs 2000–2009), organ transplanted, EBV status, anemia, hypoalbuminemia, elevated LDH, extranodal sites involvement, grafted organ involvement, stage at diagnosis did not correlate with the OS in the univariate analysis. Using the recursive partitioning modeling, a new prognostic score was developed: ECOG score (0-1 vs 2–3), age (pediatrics [<16 year old], adults [>= 16 and <60 year old] and elderly [>60 year old]) and CD 20 status (positive vs negative) provided a tree with 5 nodes (figure 1), separating the patients into 4 risk categories. The low-risk group included pediatric patients with ECOG score of 0–1 (median OS not reached); the intermediate-low-risk group included adults with an ECOG score of 0–1 (median OS of 6.8 years); the intermediate-high-risk group included elderly with ECOG score 0–1 or pediatrics and adults with an ECOG score of 2–4 and CD20 positive or n/a (median OS of 1.8 years); the high-risk group included any patient with an ECOG score of 2–4 and CD20 negative, and elderly patients with CD20 positive or n/a (median OS of 1.3 months). In addition, in the group of adult patients with DLBCL PTLD and pPTLD (61 total), we analyzed the impact on OS of Rituximab treatment, as single agent or in combination with chemotherapy, compared to chemotherapy or immunosuppressant tapering alone. OS curves of patients treated with and without Rituximab adjusted by ECOG score, are shown in figure 2. The median OS of patients treated without rituximab with ECOG score 0–1 (18 patients) was 10.5 years, with ECOG 2–4 (13 patients) was 1.5 months compared to a median OS of 2.7 years in the rituximab group with ECOG score 0–1 (19 patients), and 1.2 years in the rituximab group with ECOG score 2–4 (11 patients) (p=0.8). This series proposed a new prognostic model for patients with PTLD, based on ECOG score, age and CD 20 expression. Interestingly, in our series, in a homogeneous population of adult patients with DLBCL and p-PTLD, the use of rituximab as single agent or in combination, compared to chemotherapy and immunosuppression tapering, did not show a survival benefit. Disclosures: O'Connor: Allos Therapeutics, Inc.: Research Funding.

scholarly journals Gestational trophoblastic neoplasia: Retrospective analysis of clinical profile, treatment pattern and outcome

2016 ◽  
Author(s):  
Paramjeet Kaur ◽  
Ashok K. Chauhan ◽  
Anil Khurana ◽  
Yashpal Verma ◽  
Nupur Bansal
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Hydatidiform Mole ◽  
Single Agent ◽  
High Risk Group ◽  
Treatment Pattern ◽  
Gestational Trophoblastic Neoplasia ◽  
Trophoblastic Tumor ◽  
Villous Trophoblast ◽  
Invasive Mole

Background: Gestational trophoblastic disease is a spectrum of cellular proliferation arising from the placental villous trophoblast. Gestational triphoblastic neoplasia (GTN) is a collective term for GTD that invade locally or metastasize. GTD includes hydatidiform mole (complete and partial) and GTN include invasive mole, choricocarcinoma, placental site trophoblastic tumor and epitheliod trophoblastic tumor. Aim: To evaluate clinicopathological profile, treatment pattern and clinical outcome in patients with gestational trophoblastic neoplasia (GTN). Materials and Methods: Twelve cases of gestational trophoblastic neoplasia treated between 2012 to November 2015 in deptt of Radiotherapy – II, PGIMS, Rohtak were evaluated in this retrospective study. Data was analyzed on the basis of age, histopathology, stage, type of treatment received and treatment related toxicities. Disease free survival was estimated. Results: Out of 12 women 7 (58 %) had hydatidiform mole, 4 (33%) invasive mole and 01 (8%) had choriocarcinoma. All the cases were given chemotherapy. Two patients had low risk disease. Among high risk group seven patients had score of less than 7 and five patients had risk score of 7 or higher. Five patients were given single agent methotrexate, seven patients received multidrug regimens. All patients are on regular follow up. One patient (high risk group) expired as she did not receive treatment. Conclusion: GTN are rare and proliferative disorders with proper diagnosis and treatment most of the cases are amenable to treatment with favorable outcome.

scholarly journals Prediction of Prognosis in Adult Patients With Carbapenem-Resistant Klebsiella pneumoniae Infection

2022 ◽  
Vol 11 ◽  
Author(s):  
Jihui Chen ◽  
Yu Yang ◽  
Huimin Yao ◽  
Shuhong Bu ◽  
Lixia Li ◽  
...  
Keyword(s):  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Treatment Effectiveness ◽  
Risk Group ◽  
Clinical Information ◽  
Tertiary Hospital ◽  
High Risk Group ◽  
Adult Patients ◽  
Carbapenem Resistant ◽  
Prediction Of Prognosis

ObjectiveCarbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with poor patient outcomes. We aimed to analyze the clinical information of adult patients with CRKP infection in order to establish a nomogram for mortality risk as well as to determine the treatment effectiveness of different antimicrobial regimens.MethodsAdult patients diagnosed with CRKP infection in a tertiary hospital in Shanghai between September 2019 and March 2021 were included. The clinical characteristics and clinical outcomes of these patients were analyzed.ResultsA total of 199 cases of CRKP infection were examined. Five factors, namely age ≥65 years, respiratory failure, Sequential Organ Failure Assessment score, serum procalcitonin ≥5 ng/mL, and appropriate treatments in 3 days, were found to be associated with 30-day mortality. Upon incorporating these factors, the nomogram achieved good concordance indexes of 0.85 (95% confidence interval [CI]: 0.80–0.90) and well-fitted calibration curves. Receiver-operating characteristic curves for 7-, 15-, and 30-day survival had areas under the curve of 0.90, 0.87, and 0.88, respectively. Three-drug combination therapy was observed to be associated with lower mortality in the high-risk group (adjusted hazard ratio = 0.24, 95% CI: 0.06–0.99) but not in the low-risk group. Ceftazidime–avibactam, fosfomycin, and amikacin were effective against infections caused by CRKP. Tigecycline improved the treatment efficiency in 7 days, but a trend toward increased mortality was seen (HR, 1.69; 95% CI: 0.98–2.94; P = 0.061).ConclusionThe antimicrobial regimen efficacy data and the predictive nomogram established in this study can help clinicians in identifying high-risk adult patients with CRKP infection, improving the therapeutic effect, and reducing mortality.

Single Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia: Long Term Follow-up Data.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 846-846
Author(s):  
Vikram Mathews ◽  
Biju George ◽  
Kavitha M Lakshmi ◽  
Auro Viswabandya ◽  
Ezhilarasi Chendamarai ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Single Agent ◽  
High Risk Group ◽  
Reproductive Age ◽  
Newly Diagnosed ◽  
Long Term Follow Up ◽  
Good Risk

Abstract Abstract 846 We had previously reported a well tolerated regimen using single agent arsenic trioxide (ATO) (Blood 2006:107; 2627) leading to durable remissions in patients with newly diagnosed acute promyelocytic leukemia (APL). Briefly, the regimen consisted of ATO (10mg/day for adults and 0.15mg/kg/day for pediatric patients) for up to 60 days in induction; this was followed by a 28 day consolidation after a 4 week break. Four weeks after completion of consolidation, patients received ATO for 10 days/month for 6 months. A concern with the previous report was the relatively short duration of follow up. Here we report the long term follow-up data of the same cohort. As previously reported, 72 newly diagnosed cases of APL were enrolled. 62 patients (86.1%) achieved hematological remission. The remaining died prior to achieving remission. There were no primary induction failures. Twenty two (30.6%) of these patients were considered good risk group (WBC count at diagnosis <5×109/L and a platelet count >20×109/L), the rest were considered high risk. Since publication of the last report an additional 7 patients have relapsed to give a total of 13 relapses, 2 were in the good risk group and the remaining 11 in the high risk group. The relapses in the good risk group were salvaged with an autologous SCT and have durable continued second remissions. The median time to relapse was 1.5 years. Five (38.52%) of these relapses occurred beyond 2 years and included both relapses in the good risk group. At a median follow-up of 58 months the 5-year Kaplan-Meier overall survival (OS), event free survival (EFS) and disease free survival (DFS) of the entire cohort was 74.22±5.26%, 68.93±5.52% and 80.00±5.17% respectively. The 5-year OS and EFS of the good risk and high risk group was 100±00% vs. 63.30±6.9% and 90.00±6.71% vs. 59.66±6.99% respectively. Beyond induction, all deaths followed relapse of disease. There were no second malignancies reported. Besides the previously reported toxicities, which were mild and transient in most cases, there were no new toxicities that were reported on continued follow up of these cases. Since completion of therapy, in spite of counseling and advising against pregnancy, 3 males and 4 females in the reproductive age group have had 8 normal children. No abortions, still births or fetal defects were reported among patients in the reproductive age group in this cohort. Hair and nail samples from 5 cases that had completed maintenance therapy more than 24 months earlier have been collected for analysis, the results of which are awaited. At our center the cost of administering this regimen is a quarter of that of a conventional ATRA plus anthracycline based regimen. Additionally, after the initial induction therapy the rest of the treatment did not require hospital admission nor did it result in any Grade III/IV hematological toxicity. Single agent ATO based regimen as reported previously is well tolerated, results in durable remissions and does not have any significant late side effects. In the good risk group it is associated with excellent clinical outcomes while in the high risk group additional interventions are probably required to reduce the risk of late relapses. In a resource constrained environment it is probably the best option. Disclosures: No relevant conflicts of interest to declare.

Preliminary Results of a Phase II Study of Low Dose Decitabine as a Single Agent in Older Patients (age≥60) with Previously Untreated Acute Myeloid Leukemia (AML)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2957-2957 ◽  
Author(s):  
William Blum ◽  
Rebecca Klisovic ◽  
Shujun Liu ◽  
Ramiro Garzon ◽  
Cheryl Kefauver ◽  
...  
Keyword(s):  
High Risk ◽  
Low Dose ◽  
De Novo ◽  
Phase Ii Study ◽  
Risk Group ◽  
Single Agent ◽  
Initial Response ◽  
Clinical Results ◽  
Median Number ◽  
High Risk Group

Abstract The hypomethylating agent decitabine inhibits DNA methyltransferase (DNMT) enzymatic activity and is approved by the FDA for treatment of myelodysplastic syndromes. We previously performed a phase I trial in AML of decitabine (with or without the histone deacetylase inhibitor valproic acid); the trial was designed to establish a biologically effective dose (BED) of decitabine based on drug-induced re-expression of methylated and silenced genes. With the derived BED of 20mg/m2/day given for 10 days, every 4 weeks, clinical activity was observed in previously untreated older AML patients (pts, CR in 4/12); clinical response correlated with gene re-expression (Blum, JCO 2007). The addition of tolerable doses of valproic acid did not appear to improve clinical results or increase gene re-expression compared to decitabine alone. Therefore, we designed a phase II study of single agent decitabine for previously untreated AML pts of age≥60 who were not candidates for intensive chemotherapy (or who refused it). Performance status was ECOG &lt;3. All pts received induction with decitabine at 20mg/m2 IV over 1 hour on days 1–10 of a 28 day cycle. The schedule for subsequent cycles was customized for each patient based on clinical response and/or toxicity (e.g., myelosuppression). Pts with persistent AML at the end of a cycle received a repeat of the 10 day treatment. In contrast, pts with &lt;5% blasts received decitabine as consolidation for only 5 days/cycle (every 4 weeks for 1 year). For CR/CRi patients, the decitabine schedule could be reduced further to 4 or 3 days/cycle for Grade 4 neutropenia lasting more than 2 weeks, if applicable. 33 pts were enrolled; accrual was completed in 13 months. Pts had a median age of 74 years (range, 60–83); 24 pts were age≥70. 18 pts had de novo AML; 15 had secondary or t-AML. Pts had a median presenting white blood cell count of 2,400/uL (range, 400–58,800/uL) with median marrow blasts of 44% (range, 21–92%). 13 pts had complex karyotype (≥3 abnormalities); 12 had normal karyotype; one patient had t(8;21), and the rest had other abnormalities (with one unknown). This was a high risk group by any comorbidity measure. Scoring was as follows on four high-risk factors of age ≥70, antecedent hematologic disorder, unfavorable karyotype, and ECOG 2: 16 pts had 3+ risk factors; 15 had two, and the other 2 pts had one risk factor. Using the transplant comorbidity index for older AML pts (HCT-CI; Giles, BJH 2007), pts had scores of 3+ (N=18), 1–2 (N=10), or 0 (N=5). The median number of cycles received to date is 3 (range, 1–10); 17 pts continue to receive study therapy. 10 pts have received 4+ cycles. Of the first 22 consecutive pts enrolled, 11 achieved CR (50%); 4 more have achieved CRi by IWG criteria for response (Cheson, JCO 2003). 11 pts are &lt;3 months since entry onto the study, with response evaluations ongoing. The response rate was similar between cytogenetic risk subgroups and in both de novo and secondary AML. 4 pts who achieved CR subsequently relapsed, with CR duration of 9, 6, 6, or 2 months, respectively. The other CR pts have maintained ongoing responses for 2–11+ months. 9/11 pts who achieved CR required only 1 cycle of induction therapy (10 day course) before initial response was achieved (CR, N=2; CRi, N=7). For pts who had CRi as initial response, the median number of additional cycles to achievement of full CR was 1 (range, 1–3). In this high risk group, death within 8 weeks of any cause occurred in 4 pts and was related to infection in each case. Though therapy was often administered in the outpatient clinic, febrile neutropenia and infections in the setting of drug and/or disease-related myelosuppression requiring hospitalization during the induction courses were frequent, occurring in nearly all pts. Post-CR therapy, however, was very well tolerated with no hospitalizations for complications during consolidation courses. In conclusion, decitabine in this novel schedule of induction with outcome-adapted modification of consolidation therapy was highly active and well tolerated by most in this poor risk cohort of older AML pts. Clinical results compare favorably to those seen in this population with low dose clofarabine (Erba, ASCO 2008a) or decitabine-5 day schedule (Cashen, ASH 2006a). Correlative studies including re-expression of epigenetically silenced genes, target gene promoter methylation, and global DNA methylation are ongoing.

scholarly journals The QT Interval in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine/Azithromycin

2020 ◽  
Author(s):  
Ehud Chorin ◽  
Matthew Dai ◽  
Eric Shulman ◽  
Lalit Wadhwani ◽  
Roi-Bar-Cohen ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
High Risk ◽  
Qt Interval ◽  
Risk Group ◽  
Strong Predictor ◽  
High Risk Group ◽  
Adult Patients ◽  
Qtc Prolongation

AbstractWe report the change in the QT interval in 84 adult patients with SARS-CoV-2 infection treated with Hydroxychloroquine/Azithromycin combination. QTc prolonged maximally from baseline between days 3 and 4. in 30% of patients QTc increased by greater than 40ms. In 11% of patients QTc increased to >500 ms, representing high risk group for arrhythmia. The development of acute renal failure but not baseline QTc was a strong predictor of extreme QTc prolongation.

scholarly journals Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLG-APL2016 Protocol Study

2021 ◽  
pp. JCO.20.03096
Author(s):  
Huyong Zheng ◽  
Hui Jiang ◽  
Shaoyan Hu ◽  
Ning Liao ◽  
Diying Shen ◽  
...  
Keyword(s):  
High Risk ◽  
Pediatric Patients ◽  
Risk Group ◽  
High Risk Group ◽  
Event Free Survival ◽  
Free Survival ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Standard Risk

PURPOSE Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes. METHODS We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and FLT3-ITD mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years. RESULTS We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group ( P = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group ( P = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment. CONCLUSION Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.

scholarly journals Radical prostatectomy as radical cure of prostate cancer in a high-risk group: A single-institution experience

2012 ◽  
Vol 1 (2) ◽  
pp. 337-342 ◽  
Author(s):  
NOBUKI FURUBAYASHI ◽  
MOTONOBU NAKAMURA ◽  
KEN HISHIKAWA ◽  
ATSUSHI FUKUDA ◽  
TAKASHI MATSUMOTO ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Risk Group ◽  
High Risk Group ◽  
Radical Cure ◽  
Single Institution ◽  
Group A

scholarly journals Gestational trophoblastic neoplasia: Retrospective analysis of clinical profile, treatment pattern and outcome

2016 ◽  
Author(s):  
Paramjeet Kaur ◽  
Ashok K. Chauhan ◽  
Anil Khurana ◽  
Yashpal Verma ◽  
Nupur Bansal
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Hydatidiform Mole ◽  
Single Agent ◽  
High Risk Group ◽  
Treatment Pattern ◽  
Gestational Trophoblastic Neoplasia ◽  
Trophoblastic Tumor ◽  
Villous Trophoblast ◽  
Invasive Mole

Background: Gestational trophoblastic disease is a spectrum of cellular proliferation arising from the placental villous trophoblast. Gestational triphoblastic neoplasia (GTN) is a collective term for GTD that invade locally or metastasize. GTD includes hydatidiform mole (complete and partial) and GTN include invasive mole, choricocarcinoma, placental site trophoblastic tumor and epitheliod trophoblastic tumor. Aim: To evaluate clinicopathological profile, treatment pattern and clinical outcome in patients with gestational trophoblastic neoplasia (GTN). Materials and Methods: Twelve cases of gestational trophoblastic neoplasia treated between 2012 to November 2015 in Department of Radiotherapy – II, PGIMS, Rohtak were evaluated in this retrospective study. Data was analyzed on the basis of age, histopathology, stage, type of treatment received and treatment related toxicities. Disease free survival was estimated. Result: Out of 12 women 7 (58 %) had hydatidiform mole, 4 (33%) invasive mole and 1 (8%) had choriocarcinoma. All the cases were given chemotherapy. Two patients had low risk disease. Among high risk group seven patients had score of less than 7 and five patients had risk score of 7 or higher. Five patients were given single agent methotrexate, seven patients received multidrug regimens. All patients are on regular follow up. One patient (high risk group) expired as she did not receive treatment. Conclusion: GTN are rare and proliferative disorders with proper diagnosis and treatment most of the cases are amenable to treatment with favorable outcome.

The Outcome Of Patients With Post Transplant and Immunodeficiency Associated Lymphoproliferative Disorder: The BCCA Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4390-4390
Author(s):  
Amrit Kahlon ◽  
Graham W. Slack ◽  
Yuhua Sun ◽  
Richard Klasa ◽  
Laurie H. Sehn ◽  
...  
Keyword(s):  
High Risk ◽  
Hodgkin Lymphoma ◽  
Combination Chemotherapy ◽  
Research Funding ◽  
Single Agent ◽  
Lymphoproliferative Disorders ◽  
Grey Zone ◽  
Post Transplant ◽  
Single Agent Chemotherapy

Abstract Background Post-transplant lymphoproliferative disorders (PTLD) develop in the setting of immunosuppression following solid organ transplant or allogeneic stem cell transplant (alloSCT). Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (‘PTLD-like’) can occur with the use of immunosuppressive agents for autoimmune or related disorders. The optimal first-line treatment and risk stratification tool for PTLD remains unclear and rituximab (R) monotherapy is often used following a reduction of immunosuppression (RIS), reserving combination chemotherapy for those failing this initial approach. However, this approach may not be suitable in those with high risk disease. The aim of this study was to review the outcome of patients with PTLD and PTLD-like disease, Methods Using the British Columbia Cancer Agency (BCCA) Lymphoid Cancer Database, all patients diagnosed with PTLD and PTLD-like conditions from 1981-2013 were identified, excluding primary CNS lymphoma, low-grade lymphomas and HIV associated lymphomas. Results 104 patients were identified: 86 PTLD and 18 PTLD-like. PTLD: Median age 47 y (range 6-71); 64% male; 60% late onset (> 1 year from transplant); 71% extranodal (EN) disease; 14% graft involved; 49% elevated LDH (n=36, missing n=13); 59% PS > 2 (n=45, missing n=10); 60% prior renal transplant. Pathology: 57% EBV positive (n=43, missing n=11); 2% early lesions, 13% polymorphic, 79% monomorphic (83% DLBCL), 1.1% classical Hodgkin lymphoma (CHL) and 4.7% unknown. All patients underwent initial RIS, followed by: observation (n=23, 27%), single agent rituximab (n=37, 43%), anthracycline based combination chemotherapy + R (n= 9 (n=6 + R), 10%), single agent chemotherapy + R (n=8 (n=4 + R), 9%); 4 (5%) were too frail to treat. With a median follow-up for living patients of 4.0 y (range 0.8-16.2 y), the 3-y OS and 3-y TTP were 50% and 48%, respectively. Polymorphic cases had a more favorable outcome compared to monomorphic cases with a 3-y OS of 91% vs. 45% (p=0.029) and a 3-y TTP of 73% vs. 44% (p=0.037). Monomorphic PTLD prognostic factors (n=63): In univariate analysis for TTP, an elevated LDH (p=0.006), poor PS >2 (p=.0012), EN sites > 1 (p=0.005), B symptoms (p=0.0019) and GI (p=0.022), kidney (p=0.009) and hepatic (p<0.00001) involvement were all associated with an inferior TTP. Similarly, elevated LDH (p= 0.028), poor PS (p=0.0001) and kidney involvement (p=0.027) were associated with a poor OS. A high IPI score was associated with an inferior outcome: 3-y OS and 3-y TTP for low (0,1) (n=20), intermediate (2,3) (n=34) and high risk (4,5) (n=14) groups were 69%, 40%, and 21% (p=0.03) and 83%, 28%, and 14% (p<0.0001), respectively. For monomorphic DLBCL cases receiving single agent rituximab (n=29), a higher IPI was also associated with a worse 3-y OS (76%, 64%, and 20%, p=0.018) and 3-y TTP (67%, 27%, and 20%, p=0.03) for the low, intermediate and high risk groups, respectively. PTLD-like: Median age 63 y (range 26-74); 50% male; 51% EN disease; 33% LDH elevated (n=6); 44% PS > 2 (n=7, missing n=2); 92% EBV positive (n= 12, missing n=5). Pathology: 1 polymorphic (6%); 15 monomorphic (83%) (DLBCL n=11, 73%, DLBCL/CHL grey zone lymphoma n=2, 13%), 1 CHL (6%), 1 Hodgkin-like (6%), 1 unknown (6%). The majority of patients had a history of rheumatoid arthritis (n=10, 56%) and had been on treatment with methotrexate (n=10, 56%). The median time from onset of autoimmune disorder to the development of PTLD-like disease was 11 y (0.16-50) and the median duration of drug exposure prior to the development of the PTLD-like disease was 5 y (0.16-15y). All patients underwent RIS, followed by observation (n=6, 32%); single agent rituximab (n=4, 21%); anthracycline based combination chemotherapy + R (n=6, 37%; R, n=4); or single agent chemotherapy + R (n=1, 5.3%); 1 was too frail. With a median follow-up of 4.9 y (range 0.3-17 y), the 3-y TTP and OS were 65% and 77%, respectively. Conclusion For PTLD, a select group of patients with a low IPI score appear to have high cure rates with single agent rituximab. For those with multiple IPI factors a risk-adapted strategy with earlier use of chemotherapy may be preferred. In the group with PTLD-like disease we observed Hodgkin lymphoma and Hodgkin-like proliferations but also grey zone lymphomas, the latter of which has not been previously reported. Patients with PTLD-like disorders have a more favorable outcome than those with PTLD. Disclosures: Klasa: Roche Canada: Research Funding. Sehn:Roche/ Genentech: Consultancy, Honoraria, Research Funding. Villa:Celgene: Honoraria; Lundbeck: Honoraria; Roche: Honoraria, Research Funding. Shenkier:Roche Canada: Research Funding. Connors:Roche Canada: Research Funding; F Hoffmann-La Roche: Research Funding. Savage:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding.

scholarly journals Multidrug resistance gene 1 polymorphisms in pediatric patients with leukemia at a national referral hospital in Indonesia

2017 ◽  
Vol 9 (5) ◽  
pp. 625-630 ◽  
Author(s):  
Rina Mutiara ◽  
Bernadius Agustinus ◽  
Christian Badia Sitompul ◽  
Amarila Malik ◽  
Djajadiman Gatot ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
High Risk ◽  
Resistance Gene ◽  
Pediatric Patients ◽  
Risk Group ◽  
Pediatric Population ◽  
Lymphoblastic Leukemia ◽  
High Risk Group ◽  
Multidrug Resistance Gene ◽  
Standard Risk

Abstract Background Acute lymphoblastic leukemia (ALL) is the most prevalent cancer in the pediatric population. From 25% to 30% of patients with ALL will have a relapse that leads to death when they are teenagers. At Cipto Mangunkusumo Hospital, 40% of 126 pediatric patients with ALL relapsed from 2005 to 2011. A multiple variant of multidrug resistance gene 1 (MDR1) is C3435T, which can be used to understand the genetic basis of susceptibility to relapse. Objectives To identify the profile of MDR1 polymorphism in pediatric Indonesian patients with ALL. Methods We collected data from 44 patients with ALL who attended Cipto Mangunkusumo Hospital between January and June 2014. We investigated a silent C3435T polymorphism in MDR1 exon 26 with polymerase chain reaction- restriction fragment length polymorphism using MboI. Results There were 32 male and 12 female patient participants in this study. Eighteen patients were 1–3 years old and 26 were over 3 years. The mean age at 1–3 years was 2.4 ± 0.86, and over 3 years it was 6.3 ± 2.67 years. There were 27 patients with ALL in the standard risk group and 17 in the high risk group. We determined that the 25 samples from patients with ALL in the standard risk group were not digestible (allele T) and the 6 samples from patients with ALL in the high risk group were digestible (allele C). Conclusions The prevalence of the T allele was higher than that of the C allele in pediatric Indonesian patients with ALL.

Sign in / Sign up

Export Citation Format

Share Document