scholarly journals Incidence and Risk Factors for Second Malignancies after Transplant in Long Term Survivors of Allogeneic Haematopoietic Stem Cell Transplant: A Single Centre Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3417-3417
Author(s):  
Mohammed Snober ◽  
Richard Syzdlo ◽  
Jane Apperley ◽  
Aristeidis Chaidos ◽  
Edward Kanfer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Second Malignancy ◽  
Second Malignancies ◽  
Additional Information ◽  
Increased Risk ◽  
High Index Of Suspicion

Abstract Second malignancies are well recognised complications of haematopoietic stem cell transplantation (HCT). The incidence increases with time after HCT with no evidence of plateau with follow up times of 15-20 years. In this study we have investigated patients over a 37-year period to include all patients transplanted at The Hammersmith hospital since 1979 who survived a minimum of two years after transplant. We aimed to describe the post-transplant malignancies (PTM) that occurred and calculate the cumulative incidence with time. Methods Data was gathered through internal databases and supplemented with case notes with all patients giving consent for their data to be used in clinical studies. Additional information on patients who had died at the time of analysis included review of death certificates for evidence of a second malignancy. If a patient had not been seen within 5 years evidence of death was sought on the NHS Spine and if apparently still alive, the date of last follow up was taken as follow up time. Second malignancies included second solid neoplasms (SSN), non-melanoma skin cancer (NMSC) and leukemias/lymphomas. These were recorded and categorised in accordance with the international classification of disease for oncology (ICD-O). Results 697 patients survived a minimum of two years after HCT between 1979-2018, 60% of whom were male. Follow up was prolonged with 20% of our 2-year survivors followed up for more than 20 years. The majority of patient (80%) were aged between 20-50 at time of HCT. (median age 35.6y, range 4-69) with only 7 patients < 10 y at HCT. The most frequent diagnoses were CML (n=463) or AML (n=103). The majority of patients (n=538, 77%) had received TBI, and the most frequently used conditioning was Cyclo-TBI (479 patients, 69%). At the time of analysis, 222 patients had died and of the remaining 475, 107 were lost to follow up. We identified 97 PTM in 87 patients a median of 14.2 years post HCT (range 0.8-35.9 years). These included 58 cases of SSN, 28 cases of NMSC and 11 cases of leukemia or lymphoma. The most frequent SSN were breast (n=12), tongue (n=7), colorectal (n=6), melanoma (n=5), bladder (n=4), thyroid (n=3) and oesophagus (n=3). Of 28 patients with NMSC, 19 developed one or more BCC and 9 developed SCC. The cumulative incidence of PTMs did not plateau with time. Cumulative incidences were as follows with 95% confidence intervals (CI) in parentheses: 4.9% (3.3-7.3) at 10 years, 12.2% (9.1-16.2) at 15 years, 22.5% (17.6-28.9) at 20 years, 39% (30.3-48.4) at 25 years and 53% (41.6-64.1) at 30 years. These data reflected the substantial increases in the CI of SSN and NMSC between these time points. For SSN the cumulative incidence increased from 3% (1.8-5) at 10 years to 37.9% (27.4-49.6) at 30 years; for NMSC the cumulative incidence increased from 1.3% (0.6-2.7) at 10 years 16.6% (9.2-28.2) at 30 years. In multivariate analyses older age (>50) at time of transplant was associated with significantly increased (p<0.01) risk of PTM with a relative risk (RR) of 4.53 (2.1-9.6). On subgroup analysis this was only relevant to SSN where the RR was 5.17 (2.2-12.1). Patient/donor sex combinations other than male patient/male donor were also at increased risk of PTM, RR 1.797 (1.1-2.9), p=0.033, and again this was only significant for SSN (RR 2.11, 1.13-3.93). Discussion and conclusions In this predominantly adult study, the cumulative incidence of SSN and NMSC increased substantially with time after HCT beyond a 10-year follow-up period. The risk was increased in patients who were >50 at time of HCT. Prolonged expert follow-up with a high index of suspicion for second malignancy in these patients is recommended to facilitate early diagnosis. Disclosures Apperley: Novartis: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau. Milojkovic:Incyte: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau.

BK Virus (BKV) Associated Haemorrhagic Cystitis Is Associated with Graft Versus Host Disease (GVHD) and Significant Morbidity Post Haematopoietic Stem Cell Transplant (HSCT).

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3040-3040
Author(s):  
Alesia Abigael Hunt ◽  
Anjum Bashir Khan ◽  
Donal McLornan ◽  
Majid A Kazmi ◽  
Matthew Streetly ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Bk Virus ◽  
Haematopoietic Stem Cell ◽  
Control Group ◽  
Cell Transplant ◽  
Haemorrhagic Cystitis ◽  
Graft Versus Host ◽  
Grade Ii

Abstract Abstract 3040 The Polyomavirus hominis 1 BK virus (BKV) is a non-encapsulated DNA virus, which infects up to 90% of the world's population, and may reactivate at times of severe immunosuppression, including post haematopoietic stem cell transplantation (HSCT). The significance of BK virus reactivation post Haematopoietic Stem Cell Transplant (HSCT) remains unclear. We collected retrospective data on viruria, viraemia, haemorrhagic cystitis (HC) and acute/chronic graft versus host disease (a/cGVHD) in patients at our institution over the period 2006 to 2011. We compared with a multivariate matched control group of 38, who did not reactivate BK. The groups were matched for age, sex, donor source and conditioning regimen including use of Alemtuzumab. Global BK reactivation incidence was 32% (38/118) of allogeneic HSCT during this period. 73% (28/38) of those who reactivated received volunteer unrelated donor (VUD) grafts, and 50% (18/38) received Alemtuzumab. Patients were sub-divided into those with high grade viraemia (HGV, VL >104 copies/ml), 47% (18/38) or low grade viraemia (LGV, VL<104 copies/ml), 53% (20/38). HGV was present in 57% of VUD transplants and 20% of sibling recipients, compared to LGV in 29% of VUDs and 70% of siblings. HGV influenced 1 year EFS; 18% versus 55% in LGV. Median OS was 173 days in HGV versus 345 days in LGV. Cumulative mortality rate in the BK group was 71% (27/38) as compared to 55% (21/38) in the control group (not significant). Relapse related mortality in the BK group was 22% (6/27) versus 57% (12/21) in the control group, at a median follow up of 229 days (p=0.088), indicating the high incidence of non-relapse causes of mortality in the BK group. 79% (30/38) of patients reactivating BK developed aGVHD, including 83% (15/18) with HGV, compared to 57% (21/37) in the control group (p=0.039). The number of patients who developed grade II-IV aGVHD in the BK group was 30/38 (79%) and 11/37 (20%) in the control group (p <0.001), figure 1. In 33% of patients BK reactivation preceded aGVHD by a mean of 12 days. 84% (27/32) of patients developed cGVHD, compared to 30% (18/30) in control group (p=0.05). Moderate-severe (NIH grade) cGVHD was more prevalent in patients reactivating BK, compared to control group; 75% (24/32) versus 3% (1/30) (p<0.001), figure 2. This data suggests the association of BK with an increased incidence of acute and chronic GVHD, and significant morbidity. Notably 10 patients developed severe complications including grade 4 HC (5/10), obstructive hydronephrosis and bladder wall dysfunction requiring invasive intervention. 7/10 (70%) of these patients had HGV; 2 patients reactivated early, failed treatment, developed obstructive renal failure and died. These patients had an increased rate of mortality compared to the whole study group (p=0.005), and all failed to achieve an EFS of over 1 year. Of note, 8.5% of all allografts developed grade 4 HC and 90% of these subsequently died. BK reactivation strongly correlates with acute and chronic GVHD and an increase in non relapse mortality. Routine surveillance for BK with risk scoring may allow earlier detection and reduced morbidity of BK and GVHD. Further prospective studies are required to understand the impact of the reactivation of the virus. Figure 1: Cumulative Incidence of acute GVHD Grade II-IV: Figure 1:. Cumulative Incidence of acute GVHD Grade II-IV: p <0.001 Figure 2: Cumulative Incidence of chronic GVHD moderate-severe: Figure 2:. Cumulative Incidence of chronic GVHD moderate-severe: p <0.001 Disclosures: No relevant conflicts of interest to declare.

Risk of secondary cancers after breast conserving therapy in Japan.

2016 ◽  
Vol 34 (3_suppl) ◽  
pp. 256-256
Author(s):  
Kenshiro Shiraishi ◽  
Tomohiro Shinozaki
Keyword(s):  
Cumulative Incidence ◽  
Breast Conserving Therapy ◽  
National Registry ◽  
Cancer Type ◽  
Secondary Malignancies ◽  
Second Malignancies ◽  
Secondary Cancers ◽  
Kaplan Meier ◽  
Increased Risk

256 Background: There is a growing body of evidence that vast majority of patients with early breast cancer who underwent breast conserving therapy (BCT) live their longer ‘cancer survivor’ lives through modern sophisticated treatment. Accordingly, second malignancies after BCT are on the rise, which are sticky dilemmas accompanied by additional anxiety and need for further medical care. Investigation of secondary malignancies should be made the first priority in Japan as the world's top country for longevity. Methods: In order to investigate the second malignancies after BCT, a cohort study was conducted based on our database from 1982 to mid-2015. Actuarial rates of second malignancies, overall (OS) and cause-specific survival (CSS), were calculated by using the Kaplan-Meier method. We calculated standardized incidence ratios (SIR) for each cancer type corresponding to the national registry. Results: 1,557 patients (49.5%) were followed-up for more than 10 years. At a median follow-up of 113 months, 180 patients had developed a second malignancy. The increases in risk were for leukemia (SIR: 3.89 (1.76–6.84)) and ovarian cancer (SIR: 3.65 (2.26–5.38)). Trends toward increased risk was seen in reno-ureteral cancer (SIR: 2.25 (0.96–4.08)) and endometrial cancer (SIR: 1.59 (0.92–2.43)) though it was not statistically significant. No increased risk was observed for other gastrointestinal and genitourinary cancer, malignant melanoma, lymphoma, thyroid or head and neck cancer. Overall 10-year cumulative incidence of OS was 93.3%, and overall 10-year cumulative incidence of CSS was 95.0%. Overall 10-year incidence of secondary cancer was 5.9%. A total number of secondary malignancies within 10 years was 157 and this number explained 84.4% of all cases observed during follow-up. Secondary cancers continued to occur afterward, and cumulative incidence at 15- and 20-years were 8.4% , and 9.6%, respectively. Conclusions: Secondary cancers after BCT continue to arise as long as patients survive. Given its nature of life-threatening to cancer survivors, attending care team must pay persistent attention to secondary malignancies especially in Japan with the longest life-span.

Long Term Molecular Remissions after Autologous Haematopoietic Stem Cell Transplant in Follicular Lymphoma.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2185-2185
Author(s):  
Séverine Lissandre ◽  
Patrick Vourch ◽  
Isabelle Desbois ◽  
Lotfi Benboubker ◽  
Caroline Dartigeas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
First Line ◽  
Molecular Remission ◽  
Remission Duration

Abstract Background and aim of the study: Autologous stem cell transplant (ASCT) has been shown to be an effective treatment for first-line and relapsed follicular lymphomas (FL). But no long term molecular remission was described. The aim of this retrospective study was to determine the clinical and molecular outcome of patients with FL who received ASCT during a 12-year period. Method: All patients who underwent ASCT for first-line or relapsed FL between January 1992 and December 2004 were included. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method and cumulative incidence of nonrelapse mortality (NRM), with relapse as a competing event, by Fine and Gray method. Patient characteristics: Seventy-one patients with a median age of 45 years and a median follow-up of 108 months were analysed. The majority were of the subtype grade 1 (57 %), had a high tumour burden (50 %) and were treated in firstline (52 %). After an anthracyclin-based induction regimen, 12 patients were in first complete remission (CR), 25 in first very good partial response (VGPR), 8 in second CR and 26 in second VGPR. They received BCNU, Etoposide, Aracytine, Melphalan (BEAM in 58 %) or Cyclophosphamide, total body irradiation (42 %) as conditioning for the ASCT. The majority of them received an unpurged graft (58%). Results : Thirty-eight patients were alive, 24 without progression between 4 and 12 years; 31 patients had died, 7 without progression. A total of 38 patients (55 %) developed recurrent lymphoma. Median OS was estimated at 8 years and 4 months. The ten-year PFS and the ten-year OS were 33 % and 47 %, respectively and the tenyear molecular PFS was 37 %. There was an apparent plateau on the remission duration curve at 32 % at 72 months and on the molecular remission duration curve at 37 % at 80 months. A plateau on the OS curve seemed to emerge at 41 % from the tenth year. Patients who received a purged graft had better OS and better PFS (median OS not reached versus 50 months, p = 0.08; median PFS not reached versus 22 months, p = 0.035) Three patients developed a secondary neoplasm and two a secondary myelodysplastic syndrome. The 10-year non-relapse mortality (NRM) was 20 %. Conclusion : This long follow-up study showed a plateau on the PFS and on the molecular PFS curves, suggesting that a selected group of patients might be cured by ASCT.

Advanced Age at Transplant Increases the Risk of Second Solid Malignancy (SSM) after Haematopoetic Stem Cell Transplantation (HSCT)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3952-3952
Author(s):  
John Murray ◽  
John Chadwick ◽  
Adrian Bloor ◽  
Jim Cavet ◽  
Mike Dennis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Second Malignancy ◽  
Single Centre ◽  
Solid Malignancy ◽  
Increased Risk ◽  
Cell Transplants ◽  
Long Term Survivors

Abstract Introduction: It is increasingly important to understand the long term risk associated with transplantation because the number of long term survivors is steadily growing. In comparison to other long term risks following transplantation like infertility, cataracts, endocrine dysfunction, etc. the risk of second malignancy is likely to be associated with increased risk of mortality and hence significant impact on survival outcomes. This retrospective, single centre analysis was undertaken to evaluate the risk of second solid malignancy in patients undergoing HSCT. Methods: From February 1973 to November 2013, 1983 patients (median age: 45yr., range: 14-76 yr.; M: 1259, F: 724) received stem cell transplants for haematological malignancies (Ac. Leuk: 507, Chr. Leuk: 97, lymphoma:645, myeloma:621, solid tumours:113). Donor was allogeneic (n=528) or autologous (n=1455) and conditioning was with (n=556) or without TBI (n=1427). Donor was sibling (n=302), matched unrelated (n=220) or cord blood (n=6). Source of stem cell was marrow (n=322), PBSC (n=1627), both (n=28) or cord blood (n=6). GVH prophylaxis included Campath in 203 cases. Of all the patients 1774 received single transplant but 209 received more than one transplant. Data was analysed as of 01/12/2013 using competing risk models with death as the competing event. Patients who developed second haematological malignacy were not included in this analysis. Results: Patient follow-up was more than 10 years in 382 cases (19%), between 5 to 10 years in 328 (17%), 1 to 5 years in 667 (34%) and less than 1 year in 606 cases (31%). Second solid malignancy developed in 70 patients with the incidence of 1% at 5yr (95% CI: 0.5-1.6), 2.2% at 10 yr (95% CI: 1.6-3.3), 4.8% at 15yr (95% CI: 3.6-6.8) and 8% (95% CI: 5.9-10.5) at 20 years. Site of second malignancy was brain (n=2), breast (n=15), cervix (n=3), GIT (n=11), genitourinary (n=9), lung (n=3), skin (n=17), head & neck (n=7), thyroid (n=3) and non EBV related lymphoma (n=3). In univariate analysis 10 yr. probability of developing SSM was not influenced by gender, stage of disease, primary diagnosis, type of HSCT, use of TBI, cranial top-up radiation, type of donor or year of transplant. It was significantly higher with use of PBSC (1.4% vs. 2.6%, p=0.02) and age above 65yr. (1.5% vs. 11%, p=0.001). In multi-variate analysis age above 65yr. (RR: 1.8, 95% CI: 1.1-2.9, p=0.02) and PBSC (RR: 9.4, 95% CI: 1-99, p=0.05) were independently associated with increased risk of SMN. 19 patients have died due to SSM (27%) and survival was significantly shorter with gastrointestinal, genitourinary and lung cancers. Conclusion: This single centre analysis shows that the risk of developing SSM increases with advancing age, longer follow-up and the survival is poor. Long term survivors of stem cell transplants need follow-up probably for life in speciality clinics. Continued vigilance, avoidance of known carcinogens and life style changes are strongly recommended. Disclosures Bloor: GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Cavet:Novartis: Research Funding; BMS: Research Funding.

scholarly journals Second Malignant Neoplasms (SMN) in Myeloma Patients Post Stem Cell Transplant (SCT)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1839-1839
Author(s):  
Samar Kulkarni ◽  
John Murray ◽  
Jim Cavet ◽  
Mike Dennis ◽  
Adrian Bloor ◽  
...  
Keyword(s):  
Stem Cell ◽  
Solid Tumours ◽  
Malignant Neoplasms ◽  
High Dose ◽  
Cell Transplant ◽  
Treatment Needs ◽  
Increased Risk ◽  
Long Term Consequences

Abstract Introduction: Recent developments in management of patients with myeloma have resulted in longer survival. Availability of newer class of agents for treatment has prolonged survival, improved quality of life and achieved better disease control. Use of SCT, either autologous (AutoSCT) and to a lesser extent allogeneic (AlloSCT) still forms an important aspect of myeloma treatment pathway. Improved survivorship mandates evaluation of long term consequences and risk of SMN is one of the most important long-term consequences affecting overall outcome. Aim: Estimate the risk of SMN post SCT in patients with Myeloma. Methods and Materials: Analysis includes 779 patients who received SCT for myeloma from January 2002 to December 2019. Data was collected using case records, electronic patient records, transplant database and information from referring hospitals. Follow-up was updated to June 2020. Results: Analysis includes 779 patients with myeloma (M: 488, F:291; median age:59yr, range: 26-75) receiving AutoSCT (n=716) or AlloSCT (n=63). Conditioning for AutoSCT was high dose melphalan in majority (n=714, 99.7%). AlloSCT conditioning was RIC (n=40/63, 63.5%) or MAC (n=23/63, 36.5%). TBI was part of conditioning in 51/779 (6.5%). There was no difference in demographics between two groups. Results: Median follow-up was 46 mo (range: 0.2-220). Second malignancy was identified in 48 of 779 cases (6.0%). SMN developed in 6/63 (10%) AlloSCT and 42/716 (6%) AutoSCT patents (p=0.25). SMN types were haematological (n=21), lymphoma (n=6) and solid tumours (n=21). MDS was the only haematological SMN in this series. Secondary MDS developed in 20/21 of AutoSCT as compared to 1/63 in AlloSCT (p=0.01). Non-haematological SMN were breast (n=3), upper GI (n=3), lower GI (n=2), hepato-billiary (n=2), prostate (n=3), skin (n=5), and unknown primary (n=1). SMN incidence was higher with increasing follow-up (2002-2014, 8%; 2015-2017, 2.8%, 2018-2019, 0%, p=0.002). There was no association with development of SMN and gender, age at transplant, type of stem cell source or transplant conditioning. Incidence of SMN was significantly higher for all sites as compared to general population. Cumulative incidence of SMN was 5% at 5 yr, and 15% at 10 yr for AutoSCT patients. Conclusion: Myeloma patients are at increased risk of SMN and need monitoring for long term side effects. Development of MDS post AutoSCT is the commonest SMN post AutoSCT but there is increased incidence of solid tumours as well. Impact of new modalities of treatment needs long term monitoring. Disclosures Bloor: Novartis: Honoraria; Kite, a Gilead Company: Honoraria.

Risk-Adapted Melphalan and Stem Cell Transplant for Systemic Light Chain Amyloidosis: A Single Institution Experience.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3109-3109 ◽  
Author(s):  
Heather Landau ◽  
Daniel E Fein ◽  
Hani Hassoun ◽  
Christina Bello ◽  
Joanne F Chou ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Novel Agents ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Related Mortality

Abstract Abstract 3109 Background: High dose melphalan (MEL) is a standard treatment for eligible patients with AL, a disease in which hematologic response is a key determinant of survival. With the advent of novel agents the role of stem cell transplant (SCT) for patients with AL is being questioned, especially given safety concerns. Yet with appropriate patient selection and the use of risk-adapted SCT (RA-SCT), treatment-related mortality (TRM) improved.(Br J Haem 2007;139:224; Bone Marrow Transplantation 2011; 46:970) Moreover, beginning in 2002, we showed in 2 consecutive phase II trials that following RA-SCT patients can safely receive consolidation with thalidomide and dexamethasone (TD) or bortezomib and D (BD), with the goal of improving hematologic response thereby extending overall survival (OS).(Br J Haem 2007;139:224; Amyloid 2010;17:80a) Consolidation was administered for patients achieving less than a complete response (CR). We now describe the outcomes of all patients with AL who underwent RA-SCT at Memorial Sloan-Kettering Cancer Center (MSKCC) since the year 2000. Methods: We performed a retrospective study to assess the OS of all patients who underwent SCT for a diagnosis of AL confirmed at MSKCC. Patients who had >2 major organs involved, NYHA class III or greater CHF, critical arrhythmias or cardiac syncope were ineligible for SCT. OS was calculated from transplant to date of death or last follow up. Median survival was estimated by Kaplan Meier methods. Log-rank test was used to determine whether survival functions differed by covariates of interest. Cumulative incidence function was used to estimate the incidence of cause-specific mortality. Results: A total of 151 patients underwent RA-SCT between February 2000 and June 2011; three lost to follow-up are excluded from this analysis. Of the remaining 148 patients 21%, 52% and 34% received RA-SCT at 100, 140 and 200mg/m2 of melphalan respectively based on age, renal function and cardiac involvement.(Blood 2002; 99: 4276) Five patients died within 100 days of SCT (TRM 3.4%). At a median follow up of 6.7 years, the median OS for all patients is 11.1 years (95% CI, 7.32 - not reached-NR) (Figure 1), and for patients who received MEL 100, 140 or 200 is 4.4 (95% CI, 2.7 – 6.3), NR and 11 years (95% CI, 8.2 – NR) respectively (P = <0.01). Cumulative incidence of disease related mortality at 2 years is 5.5%, and subsequently the rate of death from other causes exceeds that due to AL (Figure 2). Conclusions: RA-SCT for appropriately selected patients is safe and is associated with excellent long-term survival. Consolidation with novel agents may improve survival following RA-SCT and likely accounts for the similar OS seen in patients who received MEL 140 and 200. In the era of novel agents available for post-SCT consolidation, RA-SCT is an effective and important initial treatment for patients with AL. Disclosures: Landau: Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Research Funding. Hassoun:Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Giralt:Millenium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding. Comenzo:Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Machine learning predicts stem cell transplant response in severe scleroderma

2020 ◽  
Vol 79 (12) ◽  
pp. 1608-1615
Author(s):  
Jennifer M Franks ◽  
Viktor Martyanov ◽  
Yue Wang ◽  
Tammara A Wood ◽  
Ashley Pinckney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Treatment Protocol ◽  
Peripheral Blood Cell ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Intrinsic Gene

ObjectiveThe Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial demonstrated clinical benefit of haematopoietic stem cell transplant (HSCT) compared with cyclophosphamide (CYC). We mapped PBC (peripheral blood cell) samples from the SCOT clinical trial to scleroderma intrinsic subsets and tested the hypothesis that they predict long-term response to HSCT.MethodsWe analysed gene expression from PBCs of SCOT participants to identify differential treatment response. PBC gene expression data were generated from 63 SCOT participants at baseline and follow-up timepoints. Participants who completed treatment protocol were stratified by intrinsic gene expression subsets at baseline, evaluated for event-free survival (EFS) and analysed for differentially expressed genes (DEGs).ResultsParticipants from the fibroproliferative subset on HSCT experienced significant improvement in EFS compared with fibroproliferative participants on CYC (p=0.0091). In contrast, EFS did not significantly differ between CYC and HSCT arms for the participants from the normal-like subset (p=0.77) or the inflammatory subset (p=0.1). At each timepoint, we observed considerably more DEGs in HSCT arm compared with CYC arm with HSCT arm showing significant changes in immune response pathways.ConclusionsParticipants from the fibroproliferative subset showed the most significant long-term benefit from HSCT compared with CYC. This study suggests that intrinsic subset stratification of patients may be used to identify patients with SSc who receive significant benefit from HSCT.

Rituximab Administration Following Autologous Stem Cell Transplant for Multiple Myeloma Is Associated with Severe IgM Deficiency.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4897-4897
Author(s):  
Seah H. Lim ◽  
Yana Zhang ◽  
Zhiqing Wang ◽  
Rupa Varadarajan ◽  
Phillip O. Periman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
B Cells ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Control Group ◽  
Cell Transplant ◽  
Increased Risk ◽  
Igm Deficiency

Abstract Clonotypic B cells are frequently isolated from the peripheral blood of patients with multiple myeloma (MM). These clonotypic B cells may be clonogenic cells of MM. We hypothesized that rituximab may be a useful maintenance therapy in MM after autologous stem cell transplant (ASCT). The rationale was that CD20 antibody would deplete the clonotypic and, hence, clonogenic B cells to reduce the risk of disease relapse. ASC were mobilized with Cytoxan (3g/m2) and G-CSF from patients with MM. Two weeks after ASC collection, high dose IV melphalan (200 mg/m2) was administered followed 24 hours later by the infusion of at least 2x106/kg CD34+ cryopreserved ASC. Rituximab infusion (375 mg/m2) was started on day +30. Each patient received one antibody infusion every 3 months for 2 years or until disease progressed. All patients continued on monthly zoledronate and did not receive any other antimyeloma treatment. A total of 10 patients have been treated. Seven patients who have had post-transplant follow-up periods of &gt;12 months were evaluated. The immunoglobulin recovery and incidence of infections in this group of patients were compared to 6 patients with MM who have undergone an ASCT without rituximab maintenance. The total normal IgM level in all 7 patients was severely depressed following rituximab administration. IgG and IgA were variably affected in these patients. The IgM immunosuppression was prolonged and consistent, being seen in all patients, regardless of the disease status after transplantation. In contrast, the control group showed normalization of the total IgM levels by 3 months after transplant. Two patients treated with rituximab received pneumococcal vaccines 12 months after transplant and neither developed any IgG response to the vaccines. The data indicate that rituximab infusion following ASCT for MM severely impaired B-cell immune reconstitution. Six of the 7 patients developed moderate to severe infections during the first 12 months after initiation of rituximab infusion. There were a total of 23 episodes of infections: 21 pneumonia and 2 septicemia (one pneumococcus and one Pseudomonas). A patient died in CR due to pneumonia. In contrast, only one episode of pneumonia was observed in the control group during the same follow-up period. Therefore, the IgM deficiency probably predisposed the patients to infection. Of the 7 patients who have had more than 12 months of follow-up periods, 4 had disease refractory to standard induction chemotherapy. Of all the 10 patients treated, 6 achieved CR (2 were in CR before treatment, 2 achieved CR 3 months and 2 achieved CR 6 months after starting rituximab). All 4 patients with refractory MM (all had a follow-up of more than 12 months) achieved CR, one before and 3 after starting rituximab. One of the refractory patients has since relapsed, one died of pneumonia in CR 12 months and the other 2 have remained in CR 12+ and 18+ months after ASCT. With a follow-up of 29 months after transplant, the progression-free survival was 56.5% and the overall survival 71.4%. Rituximab infusion after ASCT for MM is therefore associated with severe IgM deficiency and an increased risk of infection. Further works are needed to determine the antitumor activities of rituximab in MM in the setting of minimal residual disease, but this should only be carried out with special attention to the prevention of infection.

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