PMID- 29949186
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20181211
IS  - 1600-0609 (Electronic)
IS  - 0902-4441 (Linking)
VI  - 101
IP  - 3
DP  - 2018 Sep
TI  - Outcomes of second-line treatment after fludarabine cyclophosphamide and 
      rituximab in patients with chronic lymphocytic leukemia outside clinical trials.
PG  - 399-406
LID - 10.1111/ejh.13129 [doi]
AB  - OBJECTIVE: To evaluate disease characteristics and long-term outcomes in patients 
      requiring second-line treatment following fludarabine, cyclophosphamide, and 
      rituximab (FCR), for relapsed/refractory disease (R/R), or following 
      discontinuation due to toxicities. METHOD: A retrospective analysis of 126 
      chronic lymphocytic leukemia patients treated with frontline FCR: 63 received 
      second-line treatment (41 relapsed, nine refractory [SD/PD], 13 prior toxicity). 
      Time to next treatment (TTNT) was calculated from beginning FCR to initiation of 
      second-line therapy. Overall and event-free survival was calculated from 
      initiation of salvage treatment (OS2/EFS2). RESULTS: Median follow-up for the 
      entire cohort was 67 and 37 months from second-line therapy. TTNT < 24 months was 
      associated with shorter OS2 and EFS2 similar to those observed with primary 
      refractory disease (OS2 19 and 23 months; EFS2 12 and 9 months for 
      TTNT < 24 months and SD/PD, respectively). TTNT >/= 24 months (71% 
      chemotherapy-based second-line), had longer OS2 and EFS2 (48 and 20 months). 
      Among the 13 patients receiving second-line therapy after discontinuing FCR due 
      to toxicity EFS2 was 41 months (59 months from initiation of FCR). CONCLUSION: 
      With limitations of sample size and treatment heterogeneity, patients progressing 
      <24 months following FCR have poor outcomes, similar to refractory patients, 
      while longer remissions are indicative of a chemoimmunotherapy sensitive disease. 
      Patients who discontinue FCR for toxicities may achieve excellent outcomes with 
      subsequent treatment.
CI  - (c) 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Joffe, Erel
AU  - Joffe E
AUID- ORCID: 0000-0002-7883-289X
AD  - Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
AD  - Department of Hematology, Rabin Medical Center, Petah Tikva, Israel.
FAU - Goldschmidt, Neta
AU  - Goldschmidt N
AD  - Department of Hematology, Hadassah Medical Center, Jerusalem, Israel.
AD  - Faculty of Medicine, Hebrew University, Jerusalem, Israel.
FAU - Bairey, Osnat
AU  - Bairey O
AD  - Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
AD  - Department of Hematology, Rabin Medical Center, Petah Tikva, Israel.
FAU - Fineman, Riva
AU  - Fineman R
AD  - Department of Hematology, Rambam Medical Center, Haifa, Israel.
FAU - Ruchlemer, Rosa
AU  - Ruchlemer R
AD  - Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel.
FAU - Rahimi-Levene, Naomi
AU  - Rahimi-Levene N
AD  - Hematology Institute, Assaf Harofe Medical Center, Zerifin, Israel.
FAU - Shvidel, Lev
AU  - Shvidel L
AD  - Faculty of Medicine, Hebrew University, Jerusalem, Israel.
AD  - Department of Hematology, Kaplan Medical Center, Rehovot, Israel.
FAU - Greenbaum, Uri
AU  - Greenbaum U
AD  - Soroka Medical Center, Beer Sheba and Ben-Gurion University, Beer Sheba, Israel.
FAU - Aviv, Ariel
AU  - Aviv A
AD  - Department of Hematology, Emek Medical Center, Afula, Israel.
FAU - Tadmor, Tamar
AU  - Tadmor T
AD  - Hematology Unit, Bnai-Zion Medical Center, Haifa, Israel.
FAU - Braester, Andrea
AU  - Braester A
AD  - Department of Hematology, Western Galilee Hospital, Nahariya, Israel.
FAU - Arad, Ariela
AU  - Arad A
AD  - Department of Hematology, Hadassah Medical Center, Jerusalem, Israel.
FAU - Polliack, Aaron
AU  - Polliack A
AD  - Department of Hematology, Hadassah Medical Center, Jerusalem, Israel.
AD  - Faculty of Medicine, Hebrew University, Jerusalem, Israel.
FAU - Herishanu, Yair
AU  - Herishanu Y
AUID- ORCID: 0000-0002-7864-0089
AD  - Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
AD  - The Hematology Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
CN  - Israeli CLL Study Group
LA  - eng
PT  - Journal Article
DEP - 20180803
PL  - England
TA  - Eur J Haematol
JT  - European journal of haematology
JID - 8703985
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - FA2DM6879K (Vidarabine)
RN  - P2K93U8740 (fludarabine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Cyclophosphamide/administration & dosage
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis/*drug therapy/mortality
MH  - Male
MH  - Middle Aged
MH  - Proportional Hazards Models
MH  - Recurrence
MH  - Retreatment
MH  - Retrospective Studies
MH  - Rituximab/administration & dosage
MH  - Treatment Outcome
MH  - Vidarabine/administration & dosage/analogs & derivatives
MH  - Young Adult
OTO - NOTNLM
OT  - CLL
OT  - FCR
OT  - relapse
OT  - salvage
OT  - therapy
OT  - toxicity
EDAT- 2018/06/28 06:00
MHDA- 2018/12/12 06:00
CRDT- 2018/06/28 06:00
PHST- 2018/05/14 00:00 [received]
PHST- 2018/06/11 00:00 [accepted]
PHST- 2018/06/28 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/06/28 06:00 [entrez]
AID - 10.1111/ejh.13129 [doi]
PST - ppublish
SO  - Eur J Haematol. 2018 Sep;101(3):399-406. doi: 10.1111/ejh.13129. Epub 2018 Aug 3.