Pulmonary Mortality after High-Dose Oral Busulfan and Autologous Stem Cell Transplant (ASCT) in Patients with Non-Hodgkin Lymphoma (NHL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1764-1764
Author(s):  
Matt Kalaycio ◽  
Brad Pohlman ◽  
Lisa Rybicki ◽  
Ronald Sobecks ◽  
Elizabeth Kuczkowski ◽  
...  
Keyword(s):  
Pulmonary Toxicity ◽  
Pulmonary Function Tests ◽  
Multivariable Analysis ◽  
Pulmonary Complications ◽  
High Dose ◽  
Cell Transplant ◽  
Lower Baseline ◽  
Increased Risk ◽  
Dose Oral ◽  
History Of

Abstract Many high-dose chemotherapy preparative regimens include agents known to cause pulmonary toxicity such as BCNU. Chemotherapy induced pulmonary toxicity may be fatal. From 1/1/93 to 12/31/04 we treated 533 NHL patients with oral busulfan 14mg/kg, VP-16 60 mg/kg, and cyclophosphamide 120 mg/kg followed by ASCT. Busulfan levels were not measured. We have followed these patients for toxicity, survival, and cause of death (COD). Of these 533 patients, 214 have died, and 53 have died without relapse (15%). Most patients (n=329; 62%) had intermediate grade NHL by the IWF system. The median age was 50 years (range, 16–77) and 43% had a history of smoking. Radiotherapy was delivered to 27% and less than 3 chemotherapy regimens were administered to 75% of patients before ASCT. Sixteen patients (3%) died of non-relapse pulmonary complications. The median time to pulmonary mortality was 5 months (range, 2.5 – 21.4 months). We routinely screen patients with pulmonary function tests including DLCO before ASCT and most patients (n=490; 92%) were screened at a median of 45 days after ASCT (range, 7–90 days). For patients for whom data was available, there was no significant decrease in the median pre-ASCT and the post-ASCT DLCO in the either the whole cohort of patients or the patients dying of pulmonary complications. However, a lower baseline DLCO before ASCT predicted for pulmonary mortality after ASCT in univariable and multivariable analysis. Patients with a baseline DLCO <94% predicted, had an increased risk of pulmonary mortality compared to patients with a baseline DLCO ≥94% predicted (p=0.016). Other significant risk factors included older age, lower baseline FEV1, prior radiotherapy, and longer time from diagnosis to ASCT. A history of smoking and disease status at the time of ASCT did not predict for pulmonary mortality. Because patients died of pulmonary complications at other institutions, we could neither determine treatment, nor confirm chemotherapy induced pulmonary toxicity. However, the early onset of pulmonary mortality after ASCT suggests the possibility of a toxic insult. Busulfan is a known pulmonary toxin, but the dose in this series of patients is relatively low and we have not seen similar pulmonary complications in 95 patients (median age 52 years) with myeloma treated with the combination of busulfan 16 mg/kg and cyclophosphamide 120mg/kg. Nonetheless, caution is warranted for older patients being treated with high-dose oral busulfan.

Increased Risk of Non-Relapse Mortality within One Year after Autologous Stem Cell Transplant in Older Adults with Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5111-5111
Author(s):  
Matt Kalaycio ◽  
Brad Pohlman ◽  
Ronald Sobecks ◽  
Steven Andresen ◽  
Kristie Summers ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pulmonary Function ◽  
Pulmonary Toxicity ◽  
Stem Cell Transplant ◽  
Pulmonary Function Tests ◽  
Autologous Stem Cell Transplant ◽  
Pulmonary Complications ◽  
Cell Transplant ◽  
Pulmonary Failure ◽  
Function Tests

Abstract The risk of early mortality after high-dose chemotherapy followed by autologous stem cell transplant (ASCT) is generally less than 5%. However, this mortality rate is often determined by deaths that occur while hospitalized or within 60–100 days of ASCT. We queried our long-term follow-up database to determine non-relapse mortality (NRM) for patients with lymphoma within 1 year of ASCT. From 1/1/99 to 3/30/04 we treated 317 evaluable lymphoma patients with busulfan 14mg/kg, VP-16 60 mg/kg, and cyclophosphamide 120 mg/kg followed by ASCT. Of these 317 patients, 21 (6.6%) had NRM within 1 year of ASCT. There were no significant differences between the 296 patients who did not die of NRM and the 21 who did with regard to diagnosis of non-Hodgkin versus Hodgkin lymphoma, exposure to radiation therapy, exposure to rituximab, stage, and disease status at the time of ASCT. However, the median age of the 21 patients who died of NRM was 56 years compared to 49 years in the 296 who did not (p = 0.003). Of the 21 patients who died of NRM, 13 (62%) died of pulmonary complications. Adult respiratory distress syndrome (ARDS) was listed as the cause of death (COD) in 5 patients, but nearly all patients died at other institutions limiting our ability to confirm COD. Pneumonia was the COD in 5 patients and pulmonary toxicity was the COD in 2 patients. We routinely screen patients with pulmonary function tests including DLCO before and approximately 42 days after ASCT. There was no significant decrease in the median pre-ASCT and the post-ASCT DLCO in either the whole cohort of patients dying of NRM or the 13 patients dying of pulmonary complications. The 8 patients with NRM, but not pulmonary complications, died of various causes including cardiac tamponade, sepsis/multi-system organ failure, cirrhosis, renal failure, and secondary malignancy. The median time from ASCT to NRM was 146 days (range 45 to 287 days). Thus, lymphoma patients remain at risk for NRM for several months after ASCT. Older patients are at particular risk. The most common COD is pulmonary failure that cannot be predicted by screening pulmonary function tests. The cause of the pulmonary failure is uncertain. Busulfan may cause pulmonary toxicity, but the dose in this series of patients is relatively low and we have not seen similar pulmonary complications in 95 patients (median age 52 years) with myeloma treated with the combination of busulfan 16 mg/kg and cyclophosphamide 120mg/kg.

scholarly journals Induction of remission with tacrolimus in a patient with severe acute, cortisone refractory ulcerative colitis and severe Covid-19 pneumonia: a case report

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Lisanne Rieker ◽  
Johannes Hofer ◽  
Golo Petzold ◽  
Volker Ellenrieder ◽  
Ahmad Amanzada
Keyword(s):  
Ulcerative Colitis ◽  
Viral Infections ◽  
Clinical Symptoms ◽  
Therapeutic Option ◽  
Viral Reactivation ◽  
High Dose ◽  
Increased Risk ◽  
Tacrolimus Therapy ◽  
Dose Oral ◽  
History Of

Abstract Background Therapy regimens used in patients with inflammatory Bowel Disease (IBD) have been associated with enhanced risk of viral infections or viral reactivation. Moreover, it is uncertain whether IBD patients have increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or infected patients may have an increased risk for severe coronavirus disease 2019 (Covid-19). Managing severe acute flare in ulcerative colitis during the Covid-19 pandemic is a challenge for clinicians and their patients. The results of the published studies mainly report on the role of the prior medication, but not how to treat severe acute flare of IBD patients with severe Covid-19 pneumonia. Case presentation We report the case of a 68-year-old patient with a long history of ulcerative colitis. He was initially admitted to an external hospital because of severe acute flare. The initiation of a high-dose oral cortisone therapy did not improve the clinical symptoms. During the inpatient treatment, he was tested positive for SARS-CoV-2. At admission to our hospital the patient showed severe flare of his ulcerative colitis and increased Covid-19 symptoms. A cortisone-refractory course was noticed. After detailed multidisciplinary risk–benefit assessment, we initiated an intravenous tacrolimus therapy and dose of prednisolone was tapered gradually. After clinical response, the therapy was adjusted to infliximab. Additionally, the Covid-19 pneumonia was kept under control despite immunosuppression and the patient could be discharged in clinical remission. Conclusions This case suggest the use of tacrolimus as a bridging therapeutic option for severe acute, cortisone refractory ulcerative colitis in Covid-19 patients. Nevertheless, the best treatment strategy for IBD patients presenting a flare during the outbreak has yet to be defined. Further data for IBD patients under calcineurin inhibitor therapy are urgently needed.

scholarly journals Older trauma patients are at high risk of delirium, especially those with underlying dementia or baseline frailty

2021 ◽  
Vol 6 (1) ◽  
pp. e000639
Author(s):  
Danielle Ní Chróinín ◽  
Nevenka Francis ◽  
Pearl Wong ◽  
Yewon David Kim ◽  
Susan Nham ◽  
...  
Keyword(s):  
Older Patients ◽  
Multivariable Analysis ◽  
Primary Outcome Measure ◽  
Hospital Length ◽  
Assessment Tools ◽  
Hospital Length Of Stay ◽  
Trauma Patients ◽  
Level Of Evidence ◽  
Increased Risk ◽  
History Of

BackgroundGiven the increasing numbers of older patients presenting with trauma, and the potential influence of delirium on outcomes, we sought to investigate the proportion of such patients who were diagnosed with delirium during their stay—and patient factors associated therewith—and the potential associations between delirium and hospital length of stay (LOS). We hypothesized that delirium would be common, associated with certain patient characteristics, and associated with long hospital LOS (highest quartile).MethodsWe conducted a retrospective observational cohort study of all trauma patients aged ≥65 years presenting in September to October 2019, interrogating medical records and the institutional trauma database. The primary outcome measure was occurrence of delirium.ResultsAmong 99 eligible patients, delirium was common, documented in 23% (23 of 99). On multivariable analysis, adjusting for age, frailty and history of dementia, frailty (OR 4.09, 95% CI 1.08 to 15.53, p=0.04) and dementia (OR 5.23, 95% CI 1.38 to 19.90, p=0.02) were independently associated with likelihood of delirium. Standardized assessment tools were underused, with only 34% (34 of 99) screened within 4 hours of arrival. On univariate logistic regression analysis, having an episode of delirium was associated with long LOS (highest quartile), OR of 5.29 (95% CI 1.92 to 14.56, p<0.001). In the final multivariable model, adjusting for any (non-delirium) in-hospital complication, delirium was independently associated with long LOS (≥16 days; OR 4.81, p=0.005).DiscussionIn this study, delirium was common. History of dementia and baseline frailty were associated with increased risk. Delirium was independently associated with long LOS. However, many patients did not undergo standardized screening at admission. Early identification and targeted management of older patients at risk of delirium may reduce incidence and improve care of this vulnerable cohort. These data are hypothesis generating, but support the need for initiatives which improve delirium care, acknowledging the complex interplay between frailty and other geriatric syndromes in the older trauma patients.Level of evidenceIII.

scholarly journals Methotrexate-Induced Neurotoxicity and Leukoencephalopathy in Childhood Acute Lymphoblastic Leukemia

2014 ◽  
Vol 32 (9) ◽  
pp. 949-959 ◽  
Author(s):  
Deepa Bhojwani ◽  
Noah D. Sabin ◽  
Deqing Pei ◽  
Jun J. Yang ◽  
Raja B. Khan ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Multivariable Analysis ◽  
Brain Magnetic Resonance Imaging ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Intrathecal Therapy ◽  
High Dose ◽  
Asymptomatic Patients ◽  
A Genome ◽  
Increased Risk

Purpose Methotrexate (MTX) can cause significant clinical neurotoxicity and asymptomatic leukoencephalopathy. We sought to identify clinical, pharmacokinetic, and genetic risk factors for these MTX-related toxicities during childhood acute lymphoblastic leukemia (ALL) therapy and provide data on safety of intrathecal and high-dose MTX rechallenge in patients with neurotoxicity. Patients and Methods Prospective brain magnetic resonance imaging was performed at four time points for 369 children with ALL treated in a contemporary study that included five courses of high-dose MTX and 13 to 25 doses of triple intrathecal therapy. Logistic regression modeling was used to evaluate clinical and pharmacokinetic factors, and a genome-wide association study (GWAS) was performed to identify germline polymorphisms for their association with neurotoxicities. Results Fourteen patients (3.8%) developed MTX-related clinical neurotoxicity. Of 13 patients rechallenged with intrathecal and/or high-dose MTX, 12 did not experience recurrence of neurotoxicity. Leukoencephalopathy was found in 73 (20.6%) of 355 asymptomatic patients and in all symptomatic patients and persisted in 74% of asymptomatic and 58% of symptomatic patients at the end of therapy. A high 42-hour plasma MTX to leucovorin ratio (measure of MTX exposure) was associated with increased risk of leukoencephalopathy in multivariable analysis (P = .038). GWAS revealed polymorphisms in genes enriched for neurodevelopmental pathways with plausible mechanistic roles in neurotoxicity. Conclusion MTX-related clinical neurotoxicity is transient, and most patients can receive subsequent MTX without recurrence of acute or subacute symptoms. All symptomatic patients and one in five asymptomatic patients develop leukoencephalopathy that can persist until the end of therapy. Polymorphisms in genes related to neurogenesis may contribute to susceptibility to MTX-related neurotoxicity.

Timing of high dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1,384 patients

Blood ◽  
2022 ◽  
Author(s):  
Matthew R. Wilson ◽  
Toby Andrew Eyre ◽  
Amy A Kirkwood ◽  
Nicole Wong Doo ◽  
Carole Soussain ◽  
...  
Keyword(s):  
High Risk ◽  
International Prognostic Index ◽  
Multivariable Analysis ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Cns Prophylaxis ◽  
Dose Methotrexate ◽  
Cns Relapse ◽  
Increased Risk

Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1,384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n=749) or at the end (n=635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.7%), with no difference between i-HD-MTX and EOT; 5.7% vs 5.8%, p=0.98, 3-year difference: 0.04% (-2.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n=1,253). In patients with high CNS international prognostic index (n=600), 3-year CNS relapse rate was 9.1% with no difference between i-HD-MTX and EOT. On multivariable analysis, increasing age and renal/adrenal involvement were the only independent risk factors for CNS relapse. Concurrent intrathecal prophylaxis was not associated with reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX versus EOT, with 308/1573 (19.6%) i-HD-MTX treatments resulting in delay to subsequent R-CHOP (median 8 days). Increased risk of delay occurred in older patients when delivery was later than day 10 in the R-CHOP cycle. In summary, we found no evidence that EOT delivery increases CNS relapse risk versus i-HD-MTX. Findings in high-risk subgroups were unchanged. Rates of CNS relapse in this HD-MTX-treated cohort were similar to comparable cohorts receiving infrequent CNS prophylaxis. If HD-MTX is still considered for certain high-risk patients, delivery could be deferred until R-CHOP completion.

Prognostic significance of rate of tumor marker (TM) decline during high-dose chemotherapy (HDCT) for relapsed germ cell tumors (rGCT).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 403-403
Author(s):  
Nabil Adra ◽  
Sandra K. Althouse ◽  
Rafat Abonour ◽  
Mohammad Issam Abu Zaid ◽  
Hao Liu ◽  
...  
Keyword(s):  
Cox Regression ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
Rank Test ◽  
High Dose ◽  
Cell Transplant ◽  
Background Rate ◽  
Significant Difference

403 Background: Rate of serum TM decline is prognostic in patients (pts) with GCT receiving first-line chemotherapy. We investigated the prognostic value of TM decline in rGCT treated with HDCT+peripheral-blood stem-cell transplant (PBSCT). Methods: 462 consecutive pts with rGCT treated with HDCT+PBSCT at Indiana University between 1/2004-1/2019. All pts were planned for 2 consecutive HDCT courses with carboplatin+etoposide per protocol (N Engl J Med 2007;357:340-8). Pts with elevated AFP and/or hCG were included (N=347). Slope and half-life (T1/2) were calculated for weekly AFP+hCG during HDCT starting with peak value at days 1-7 to avoid interference from lysis. T1/2 AFP≤7 days and hCG≤3 days were categorized satisfactory (SAT). Progression-free (PFS) and overall survival (OS) were compared for SAT vs unsatisfactory (UNSAT) using log-rank test and analyzed using Kaplan-Meier. Uni- and multivariable analysis using Cox regression model was performed. Results: 347 pts had elevated TM: 312 had non-seminoma and 35 had seminoma. Median age was 31 (range, 17-58). Primary site: testis (292), mediastinum (26), retroperitoneum/other (29). Metastatic sites included retroperitoneum (277), lung (233), liver (83), brain (77), and bone (21). At initiation of HDCT, 77 pts had elevated AFP, 222 elevated hCG, and 48 elevated both AFP+hCG. Median AFP 9 (1-21,347) and hCG 113 (1-178,140). 314 pts (91%) completed 2 planned cycles of HDCT. Overall, 46/347 pts had SAT decline (13 for AFP; 30 for hCG; 3 for both). Pts with SAT TM decline had superior outcomes compared to UNSAT: 2-yr PFS 69% vs 45% (p=0.006) and 2-yr OS 75% vs 51% (p=0.006). When evaluating each TM separately, SAT decline in hCG had superior outcomes vs UNSAT: 2-yr PFS 74% vs 47% (p=0.002). There was statistically non-significant difference for AFP: 2-yr PFS 48% vs 42% (p=0.65). In univariable analysis, UNSAT decline of hCG, but not AFP, was an adverse prognostic factor for PFS: HR=2.51 (95% CI, 1.40-4.51); p=0.002. Multivariable analysis will be presented. Conclusions: SAT rate of TM decline, particularly in hCG, predicts superior outcomes in rGCT undergoing HDCT+PBSCT. Pts with UNSAT TM decline are at higher risk for relapse and death.

scholarly journals ASXL1/SRSF2 Co-Mutated Acute Myeloid Leukemia (AML): A Rare but Distinct Subpopulation with Dismal Outcomes

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2598-2598
Author(s):  
Daniel R. Richardson ◽  
David M Swoboda ◽  
Anastasia Ivanova ◽  
Steven M Johnson ◽  
Jonathan Galeotti ◽  
...  
Keyword(s):  
Research Funding ◽  
Multivariable Analysis ◽  
Prior History ◽  
Treatment Intensity ◽  
Cell Transplant ◽  
Myeloid Neoplasm ◽  
Significant Difference ◽  
History Of ◽  
Baseline Characteristics

Background: Advances in the understanding of the genetic determinants of AML and the widespread use of next-generation sequencing (NGS) have led to the refinement of prognostically distinct molecular subgroups. Mutations in ASXL1 and SRSF2, which are common in myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPNs), rarely co-occur in patients (pts) with AML. The largest reported cohort (n=15) of ASXL1/SRSF2 co-mutated AML had no long-term survivors (Papaemmanuil et al. NEJM 2016). It remains unknown how clinical factors such as prior history of a myeloid neoplasm or intensity of treatment influence outcomes. We sought to assess the clinical characteristics and analyze outcomes in a larger cohort of pts with ASXL1/SRSF2 co-mutated AML. We hypothesized that this profile may be a genomic footprint of prior myeloid neoplasia. Methods: We conducted a multi-institutional retrospective analysis of newly diagnosed adult AML pts with both ASXL1 and SRSF2 mutations at the University of North Carolina and at Moffitt Cancer Center from 2011-2018. NGS was performed on DNA using the Illumina TruSight Myeloid 54-gene sequencing panel. The primary endpoint was overall survival (OS) defined as time from diagnosis of AML to death. Pts were stratified by secondary AML (s-AML), defined as having a documented history of MDS/MPN. Secondary outcomes included rates of complete remission (CR) and CR with incomplete hematologic recovery (CRi). Multivariable analysis was performed with baseline characteristics. Results: Forty-six pts were identified and included. The median age of pts was 72 years (range 42 - 85). Sixty-seven percent (28/42) had normal cytogenetics; 88% (37/42) were intermediate risk cytogenetics by current ELN guidelines. Sixty-one percent (n=28) were classified as having s-AML. One pt had therapy-related AML without preexisting MDS/MPN and was therefore not included in s-AML. The Figure illustrates co-existing mutations and individual responses to upfront therapy stratified by s-AML and non-s-AML. The median number of mutations was 5 (range 2 - 7). The most common co-occurring mutations were TET2 (52%), RUNX1 (35%), IDH2 (15%), and STAG2 (15%). Median OS was 7.0 months (m) (CI 5.3, 15.4). Median OS for pts with s-AML (n=28) and non-s-AML (n=18) was 6.1 and 15.4 m (p=0.05), respectively. There was no significant difference in median OS between s-AML and non-s-AML on multivariable analysis (hazard ratio (HR) = 2.56, p=0.07). Median OS did not differ by age (Age <65 years v. older, p=0.54), total # of mutations (≥ 5 v. less, p=0.73), or etiology of s-AML (MDS v. MPN, p=0.66). Twenty-two (47%) pts received upfront intensive induction chemotherapy (IC), 17 (37%) received hypomethylating agents (HMAs), and 7 pts (15%) received no AML-directed chemotherapy. Median OS did not significantly differ between pts receiving upfront IC and HMAs (15.3 v. 7.04 m, p=0.21). Among non-s-AML pts, median OS was longer in those receiving IC (n=10) versus HMAs (n=7) (15.4 v. 3.5 m, p=0.01). Among all pts receiving IC, median OS was longer in non-s-AML pts (n=10) versus s-AML pts (n=12) (15.4 v. 5.9 m, p=0.01). Median OS did not differ by treatment intensity for s-AML pts (IC v. HMA: 5.9 v. 9.9 m, p=0.38). Six pts underwent allogeneic hematopoietic cell transplant (HCT) with a median OS NR (median follow-up 15.6 m). Overall rate of CR/CRi was 35% and was similar between pts receiving IC and HMAs (45% v. 21%, p=0.29). Among pts with non-s-AML, CR/CRi rates with IC and HMAs were 70% and 29%, respectively (p=0.11). Among pts with s-AML, CR/CRi rates with IC and HMAs were 42% and 20%, respectively (p=0.38). On multivariable analysis of baseline characteristics, only ECOG performance status (PS) was significantly associated with OS (HR 2.25, p=0.01). ECOG PS remained significant (HR 2.65, p=0.03) after adjusting for HCT and treatment intensity. Conclusions: ASXL1/SRSF2 co-mutated AML represents a rare but distinct genotype with most pts having pre-existing myeloid neoplasms and associated co-mutations commonly seen in MDS/MPNs. OS is dismal regardless of age, number of mutations, treatment intensity, or prior history of myeloid neoplasm. HCT may mitigate these poor outcomes and lead to long-term survival. This represents the largest reported cohort to date of pts with ASXL1/SRSF2 co-mutated AML. Further study is warranted to inform risk stratification and prognosis of pts with ASXL1/SRSF2-mutated AML. Disclosures Foster: Bellicum Pharmaceuticals, Inc: Research Funding; Daiichi Sankyo: Consultancy; MacroGenics: Research Funding; Celgene: Research Funding. Coombs:Octopharma: Honoraria; Pharmacyclics: Honoraria; Medscape: Honoraria; Abbvie: Consultancy; Loxo: Honoraria; Cowen & Co.: Consultancy; Dedham Group: Consultancy; H3 Biomedicine: Honoraria; Covance: Consultancy. Sallman:Celyad: Membership on an entity's Board of Directors or advisory committees. Zeidner:Agios: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Honoraria; Tolero: Honoraria, Research Funding; Pfizer: Honoraria; AsystBio Laboratories: Consultancy; Merck: Research Funding; Takeda: Research Funding; AbbVie: Honoraria.

Long-term outcomes of survivors of autologous hematopoietic-cell transplantation for refractory and relapsed Hodgkin’s Disease

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6554-6554
Author(s):  
K. A. Goodman ◽  
V. Serrano ◽  
E. R. Riedel ◽  
S. Gulati ◽  
C. H. Moskowitz ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Risk Of Death ◽  
Increased Risk

6554 Background: With improvements in survival among refractory/relapsed Hodgkin’s Lymphoma (HL) patients after high-dose chemo-radiotherapy and autologous hematopoietic-cell transplant (AHCT), it is important to evaluate risk of late complications in this heavily treated population. Methods: From 1985–1998, 218 refractory/relapsed HL patients were treated on high dose chemo-radiotherapy and AHCT salvage protocols. 153 (70%) surviving ≥2 years after AHCT were analyzed. All received either radiotherapy with initial therapy or total lymphoid irradiation and involved field boost with the conditioning regimen (43%). Information from surviving patients was obtained through a self-administered questionnaire. The NDI was queried to determine vital status and cause of death. Primary endpoint was non-HL mortality, defined as mortality due to cardiac causes, infection or second malignancy (SM). Competing risk methods were used to calculate cause-specific mortality rates and examine its predictors. All events were calculated from 2 years post-AHCT to date of death/last follow-up. Results: Median follow-up time was 11 years. There have been 51 deaths, 32 due to HL and 19 due to other causes. Eleven deaths were due to SM: AML (3), MDS (2), NHL (2), NSCLC (2), gastric and colon cancer. There were 8 non-SM deaths: cardiac toxicity (4), infection, aplastic anemia, suicide, unknown causes (1 each). The 10 and 15-year overall survival (OS) rates are 64% and 57%, respectively. The 10-year cumulative incidence of death from HL and from non-HL causes were 22% and 13.5% ( table ). By univariate analysis, increased risk of death due to SM was associated only with higher age at AHCT (p=0.02). Conclusions: While HL initially accounts for the majority of deaths among patients surviving high-dose therapy, the HL mortality rate plateaus and risk of death from non-HL mortality increases after 5 years. Yet, even at 15-years, SM risk does not exceed that observed in patients treated with standard regimens. [Table: see text] No significant financial relationships to disclose.

High-dose chemotherapy (HDCT) and peripheral-blood stem cell transplant (PBSCT) in patients age 40 or older with relapsed metastatic germ-cell tumors (mGCT).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17054-e17054
Author(s):  
Vaibhav Agrawal ◽  
Sandra K. Althouse ◽  
Rafat Abonour ◽  
Mohammad Issam Abu Zaid ◽  
Cheryl K Sullivan ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Multivariable Analysis ◽  
Age Groups ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
High Dose ◽  
Cell Transplant ◽  
Platinum Refractory ◽  
Treatment Related Mortality ◽  
Related Mortality

e17054 Background: HDCT plus PBSCT is effective salvage therapy for relapsed mGCT but has potential toxicity. Historically, age ≥ 40 years has been associated with greater toxicity and worse outcomes. Methods: 445 consecutive pts with relapsed mGCT were treated with HDCT and PBSCT with tandem cycles at Indiana University from between 2004-2017 per our institutional regimen ( N Engl J Med 2007; 357:340-8). Kaplan-Meier methods and log-rank tests were used for progression free survival (PFS) analysis. Results: 329 pts were age < 40 while 116 pts were age≥40 and HDCT was being used as 2nd line in 85% and 79%, respectively. Median follow-up time was 42.5 months (range 0.3-173.4). Pulmonary metastasis was more frequent in the age < 40 group (66% vs. 41%, P < 0.001). Patients age≥40 were more likely to have seminoma (45% vs. 14%, P < 0.001), were more likely not platinum refractory (80% vs. 63%, P = 0.0010), and were less likely to complete 2 planned tandem cycles of HDCT (86% vs. 93%, P = 0.03). Grade 3 or higher toxicities were similar between either cohort, except for greater pulmonary toxicity in age≥40 group (8% vs. 2%, P = 0.02). Treatment-related mortality was similar between both age groups: 10 patients (3%) in age < 40 and 4 patients (3.5%) in age≥40 group died from complications of HDCT. 2-year PFS for age < 40 vs. age ≥ 40 was 58.7% vs. 59.6% (P = 0.76) and 2-year OS was 63.9% vs. 61.5% (P = 0.93). When evaluating patients with pure seminoma: 2- year OS for age < 40 vs. 40-50 vs. ≥ 50 was 100% vs 90.3%, vs 81.4%, respectively (P = 0.09). For patients with non-seminoma: 2-year OS was 58.1% vs. 37.1% vs. 54.2%, respectively (P = 0.01). In multivariable analysis for PFS: significant factors predicting worse outcomes included platinum refractory disease (HR = 1.55, P = 0.03), primary mediastinal non-seminoma (HR = 2.41, P = 0.03), not completing 2 cycles of HDCT (HR = 2.47, P = 0.01), and hCG > 1000 at initiation of HDCT (HR = 1.92, P < 0.001). Age was not a significant factor predicting worse outcomes. Conclusions: HDCT plus PBSCT is effective salvage therapy in pts age≥40 with relapsed mGCT. Patients age > 40 experience similar rates of toxicity and treatment-related mortality as those < 40 years of age.

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