Other Cancers in Patients with Chronic Lymphocytic Leukemia Requiring Therapy: Association with Prognostic Factors and Impact On Survival

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3896-3896
Author(s):  
Lorenzo Falchi ◽  
Michael J. Keating ◽  
Susan Lerner ◽  
Xuemei Wang ◽  
Sara S. Strom ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Median Time ◽  
Causes Of Death ◽  
Stem Cell Transplant ◽  
Lymphocytic Leukemia ◽  
Cell Transplant ◽  
Post Therapy

Abstract Abstract 3896 Chronic lymphocytic leukemia (CLL) is associated with an increased incidence of other cancers (OC). Potential risk factors for OC in CLL include immune disturbances, shared risk factors, genetic predisposition and chemotherapy. While reports on OC in patients with CLL have been typically descriptive in nature, detailed information regarding the clinical features of OC, relationship with the time of diagnosis of CLL, patient characteristics, prognostic factors and survival have been missing. We report an analysis of OC in pts with CLL requiring therapy, with a post therapy observation time of 5 years or longer. We reviewed our database and selected pts with CLL seen at our center who underwent treatment and who have a follow-up of at least 5 years after therapy. We studied pts with an OC either before or after the diagnosis and/or treatment of CLL and compared them with patients without OC. Richter's transformation of CLL was not considered an OC in this analysis. A total of 1,364 pts with CLL referred between 1963 and 2007 with a median follow up time of 8.2 years (range 5–28) were studied. Among these, we identified 324 pts (24%) with OC. Sixty-eight pts were diagnosed with >1 OC [2 OC (62 pts), 3 OC (4 pts) or 4 OC (2 pts)], for a total of 400 individual OC. Of the 324 pts with OC, OC preceded the diagnosis of CLL in 117 pts (36%), with a median time from OC to CLL of 80 (0–455) months, OC occurred after the diagnosis of CLL but before treatment in 49 pts (15%), with median time from CLL to OC of 22 (0–131) months. OC occurred after treatment of CLL in 158 pts (49%), with a median time from treatment to OC of 94 (0–304) months. The type, frequency and timing of OC are summarized in table 1. Clinical characteristics and traditional prognostic factors were not significantly different between pts with and without OC, with the exception of age, as pts with OC are older than pts without OC at the time of referral (median age: 60 vs 55 years, p<.0001). We next analyzed the distribution of the newer prognostic parameters in these two groups. Fifty-three % of pts with OC had unmutated IGHV genes, 65% were ZAP70+, 22% CD38+, 8% had del17p, 27% del11q, 22% +12, 20% negative FISH, and 23% del13q. Sixty-one % of pts without OC had unmutated IGHV genes, 58% were ZAP70+, 26% CD38+, 6% had del17p, 17% del11q, 22% +12, 26% negative FISH, and 29% del13q. A trend toward significance (p.07) for a higher incidence of del11q was observed in pts with OC. At the time of this analysis 536 (39%) pts have died and 828 (61%) are alive. One hundred seventy six/324 (54%) pts with OC are alive, vs 652/1040 (63%) pts without OC (p<.007). Median overall survival (OS) has not been reached in either pt group at a median follow up of 95 (61–284) months for pts with OC and 98 (61–340) months for pts without OC. Causes of death were: progression of CLL (99), CLL-related complications (121), OC (43), complications of stem cell transplant (16), events unrelated to CLL (39) and unknown causes (218). In pts with OC, the OC itself was the cause of death in 37%. Other causes of death were CLL/CLL-related complications in 44%, complications of stem cell transplant in 8%, and events unrelated to CLL in 11%. In contrast, in pts without OC CLL/CLL-related complications accounted for 83% of deaths, complications of stem cell transplant for 4%, and events unrelated to CLL for 13%. In conclusion, in pts with CLL requiring therapy and with post therapy follow up of >5 years, the incidence of OC is 24%. Among pts with OC, there is a trend for higher number of pts with del11q. In pts with OC, OC itself is a major cause of death, while the vast majority of deaths among pts without OC are caused by CLL or CLL-related complications. Table 1. Distribution of OC (1364 pts). Site of OC 1st case Total cases OC prior/at CLL OC after CLL After diagnosis After treatment NMSC1 124 144 41 26 77 PROSTATE 43 54 18 7 29 MELANOMA 26 34 16 2 16 BREAST 23 26 14 2 10 MDS/AML2 16 18 0 0 18 LUNG 14 21 0 1 20 NEUROENDOCRINE 3 6 1 0 5 HEAD AND NECK 12 16 3 2 11 UROTHELIAL CELL CANCERS 11 12 7 2 3 GI3 (including pancreas and liver) 10 18 4 3 11 KIDNEY 10 11 4 3 4 NHL4 and MM5 8 12 0 0 12 TESTIS/OVARY 6 6 4 0 2 THYROID 6 7 5 1 1 SARCOMAS 4 5 4 0 1 UTERUS 2 3 3 0 0 OTHERS6 6 7 3 0 4 TOTALS 324 400 127 49 224 1 non-melanoma skin cancers; 2 myelodysplastic syndrome/acute myeloid leukemia; 3 gastrointestinal; 4 non-Hodgkin's lymphoma; 5 multiple myeloma; 6 includes: brain, nasopharyngeal, penis carcinoma, mesothelioma, unknown primary. Disclosures: No relevant conflicts of interest to declare.

Clinical Profile and Outcomes of Patients with β Thalassemia Major and Hepatitis C Virus Infection Undergoing an Allogeneic Stem Cell Transplant

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4160-4160
Author(s):  
Vikram Mathews ◽  
Biju George ◽  
Kavitha M Lakshmi ◽  
Rayaz Ahmed ◽  
Aby Abraham ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Graft Failure ◽  
Stem Cell Transplant ◽  
Thalassemia Major ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Class Iii ◽  
Liver Size

Abstract Abstract 4160 There is limited data on the prevalence, clinical profile and outcome of patients with β thalassemia major (TM) who is HCV sero-positive (HCV+) prior to an allogeneic stem cell transplant (SCT). From October, 1991 to June, 2012, 370 SCT were done for TM at our center. The median age was 7.5 years (range: 2–24) and there were 232 (62.87%) males. 209 (56.5%) belonged to Lucarelli Class III. There were 44 (11.9%) cases who were HCV+, 6 (1.6%) who were HBsAg positive and 350 (94.6%) who were CMV sero-positive at the time of pre-transplant screening. HCV+ cases were significantly older and had a significantly larger liver size. There were significantly more number of HCV+ cases who were Lucarelli Class III and the median liver enzyme and ferritin levels were higher in the HCV+ group. Table 1 summarizes these and other major differences between those who were HCV positive at diagnosis and the remaining patients. The number of graft rejections was significantly higher in the HCV+ group while the TRM was comparable between the two groups. This translated into a significantly inferior event free survival (P=0.016) though the overall survival was not significantly different (P=0.140)(Table 1). It is well recognized that patients with TM are at a high risk of developing sinusoidal obstruction syndrome (SOS) post SCT. In this series, 165 (4.6%) patients developed SOS. HCV+ cases did not have a significantly higher incidence of SOS compared to those that were HCV negative. In only 3 (6.8%) of HCV+ cases was SOS the major cause of death while SOS was a major contributory factor for death in 17 (5.2%) of the remaining cases. Among the 15 (34%) of HCV+ cases that died, the major contributory cause of death was infection (40%), graft failure (20%) and SOS (20%). On a univariate cox regression analysis, HCV+ had an adverse impact on EFS (RR=1.710; 95%CI 1.066–1.744; P=0.026). However, on a forward stepwise multivariate analysis after adjusting for conventional risk factors HCV+ status did not confer an independent adverse risk factor. Of the 29 patients who are surviving, at a median follow up of 25 months, none have had progression to chronic liver disease. 20 (69%) had a normal liver function test at last follow up while only 3 have had HCV directed therapy post transplant. From August, 2009 at our center we have been using a treosulfan based conditioning regimen for our Class III patients. Among the HCV+ cases 10 were conditioned with this regimen. This regimen was well tolerated with 100% engraftment. Two patients died, one due to sepsis and the other to GVHD. In comparison, in the historical control of HCV+ cases conditioned with a conventional busulfan based regimen where there were graft rejections in 9 (26.4%) and 13 (38.2%) deaths, the major contributory cause for death being infections (46%), SOS (23%) and graft failure (23%). In conclusion HCV+ status is a surrogate risk factor for other adverse risk factors such as older age, increased liver size and inadequate medical therapy prior to SCT. After adjusting for such risk factors HCV+ cases with TM undergoing an allogeneic SCT transplant have comparable outcomes to HCV negative cases. Use of a treosulfan based regimen is well tolerated in the HCV+ group and could potentially improve the outcome in this high risk group. Table 1: Comparison of baseline characteristics and clinicical outcomes of HCV positive and vegative cases with β thalassemia major undergoing an allogeneic stem cell transplant. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Outcome of Patients with Hodgkin Lymphoma Treated with Brentuximab Vedotin for Relapse after Autologous Stem Cell Transplant: A Retrospective Analysis of the LWP-EBMT

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4018-4018
Author(s):  
Nikesh Dhiraj Chavda ◽  
Stephen Robinson ◽  
Ariane Boumendil ◽  
Irma Khvedelidze ◽  
Hervé Finel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Median Time ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Travel Grant

Around half of patients with Hodgkin Lymphoma (HL) who progress or relapse through first line therapy can be cured with salvage chemotherapy followed by autologous stem cell transplant (ASCT). However, this leaves approximately 50% of patients that will relapse after ASCT. The pivotal phase II SG035-00303 trial demonstrated that these patients can be successfully treated with Brentuximab Vedotin (BV), and a proportion of them can be long term free of disease without any further intervention. The objective of the current study was to investigate whether these findings were borne out in the real world via interrogation of the EBMT registry. We retrospectively analysed data for 101 patients with HL who had BV as their first treatment for relapse after ASCT from 2012 to 2019. The median age at ASCT was 34 years (range: 19-65), 60% being male and with 62% being in complete response (CR) at the time of ASCT. Carmustine, Etoposide, Cytarabine and Melphalan (BEAM) was the most common conditioning regimen, having been employed in 72% of the cases. The median time from ASCT to relapse was 10.1 months (interquartile range (IQR): 6.1-25.1). The median time on BV was 3.4 months (IQR: 2.1-5.24). BV treatment resulted in a best overall response rate (ORR) of 59% with a CR rate of 37%. At last follow-up only 2 patients remain on treatment with BV. The main reason for discontinuation of BV was progression which occurred in 37% of the patients. In 32 cases (33%) the treatment was stopped electively to proceed to a second transplant, and overall nearly a quarter (22%) completed the full treatment course. Only 5% of patients stopped due to toxicity (peripheral neuropathy 2 and neutropenia, infusion reaction and other, 1 each). Further therapy was given after BV in over half of evaluable patients (58%), with check point inhibitors (CPIs) being the most common agents used (24% of these). Nearly two thirds (64/101) of the patients received a second transplant, which were nearly all allogeneic stem cell transplant (alloSCT, 59/64), and most of these (49/59) with reduced intensity conditioning (RIC). 26% of the alloSCT recipients experienced grade II-IV acute graft versus host disease (GvHD) and 25% developed chronic GvHD. At last follow up, 62% of all patients were alive with a median follow-up of 25 months after starting BV. Of these, 27 had received a second transplant, who were mostly in CR at last follow up (26/27) and a further 22 had relapsed. There were 11 patients of the 63 still alive who continued to be responding to BV without further therapy with a median duration of response of 30 months. In conclusion BV use for relapse after ASCT was well tolerated generally, with only a minority of patients stopping treatment due to toxicity. However, although almost two thirds of the patients achieved a response, further treatment was often needed after BV, notably with CPIs and most patients were consolidated with a RIC alloSCT. These results confirm that only a minority of patients can achieve a durable remission with BV alone. Disclosures Brice: Takeda France: Consultancy, Honoraria; Millennium Takeda: Research Funding; BMS: Honoraria. Blaise:Molmed: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria. Stamatoullas:Celgene: Honoraria; Takeda: Consultancy. Robak:Takeda: Consultancy, Research Funding; UCB: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel grant, Research Funding; Amgen: Consultancy, Other: Travel grant; Roche: Consultancy, Other: Travel grant, Research Funding; Abbvie: Consultancy, Honoraria, Other: Travel grant, Research Funding; Gilead: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Acerta: Research Funding; Morphosys AG: Research Funding. Wahlin:Roche and Gilead: Consultancy.

Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4358-4366 ◽  
Author(s):  
Kieren A. Marr ◽  
Rachel A. Carter ◽  
Michael Boeckh ◽  
Paul Martin ◽  
Lawrence Corey
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Invasive Aspergillosis ◽  
Respiratory Virus ◽  
Stem Cell Transplant ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Cmv Disease

The incidence of postengraftment invasive aspergillosis (IA) in hematopoietic stem cell transplant (HSCT) recipients increased during the 1990s. We determined risks for IA and outcomes among 1682 patients who received HSCTs between January 1993 and December 1998. Risk factors included host variables (age, underlying disease), transplant variables (stem cell source), and late complications (acute and chronic graft-versus-host disease [GVHD], receipt of corticosteroids, secondary neutropenia, cytomegalovirus [CMV] disease, and respiratory virus infection). We identified risk factors associated with IA early after transplantation (≤ 40 days) and after engraftment (41-180 days). Older patient age was associated with an increased risk during both periods. Chronic myelogenous leukemia (CML) in chronic phase was associated with low risk for early IA compared with other hematologic malignancies, aplastic anemia, and myelodysplastic syndrome. Multiple myeloma was associated with an increased risk for postengraftment IA. Use of human leukocyte antigen (HLA)–matched related (MR) peripheral blood stem cells conferred protection against early IA compared with use of MR bone marrow, but use of cord blood increased the risk of IA early after transplantation. Factors that increased risks for IA after engraftment included receipt of T cell–depleted or CD34-selected stem cell products, receipt of corticosteroids, neutropenia, lymphopenia, GVHD, CMV disease, and respiratory virus infections. Very late IA (> 6 months after transplantation) was associated with chronic GVHD and CMV disease. These results emphasize the postengraftment timing of IA; risk factor analyses verify previously recognized risk factors (GVHD, receipt of corticosteroids, and neutropenia) and uncover the roles of lymphopenia and viral infections in increasing the incidence of postengraftment IA in the 1990s.

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