PMID- 15800326
OWN - NLM
STAT- MEDLINE
DCOM- 20050421
LR  - 20231120
IS  - 0732-183X (Print)
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 23
IP  - 10
DP  - 2005 Apr 1
TI  - Adoptive cell transfer therapy following non-myeloablative but lymphodepleting 
      chemotherapy for the treatment of patients with refractory metastatic melanoma.
PG  - 2346-57
AB  - PURPOSE: We investigated the combination of lymphodepleting chemotherapy followed 
      by the adoptive transfer of autologous tumor reactive lymphocytes for the 
      treatment of patients with refractory metastatic melanoma. PATIENTS AND METHODS: 
      Thirty-five patients with metastatic melanoma, all but one with disease 
      refractory to treatment with high-dose interleukin (IL) -2 and many with 
      progressive disease after chemotherapy, underwent lymphodepleting conditioning 
      with two days of cyclophosphamide (60 mg/kg) followed by five days of fludarabine 
      (25 mg/m(2)). On the day following the final dose of fludarabine, all patients 
      received cell infusion with autologous tumor-reactive, rapidly expanded tumor 
      infiltrating lymphocyte cultures and high-dose IL-2 therapy. RESULTS: Eighteen 
      (51%) of 35 treated patients experienced objective clinical responses including 
      three ongoing complete responses and 15 partial responses with a mean duration of 
      11.5 +/- 2.2 months. Sites of regression included metastases to lung, liver, 
      lymph nodes, brain, and cutaneous and subcutaneous tissues. Toxicities of 
      treatment included the expected hematologic toxicities of chemotherapy including 
      neutropenia, thrombocytopenia, and lymphopenia, the transient toxicities of 
      high-dose IL-2 therapy, two patients who developed Pneumocystis pneumonia and one 
      patient who developed an Epstein-Barr virus-related lymphoproliferation. 
      CONCLUSION: Lymphodepleting chemotherapy followed by the transfer of highly avid 
      antitumor lymphocytes can mediate significant tumor regression in heavily 
      pretreated patients with IL-2 refractory metastatic melanoma.
FAU - Dudley, Mark E
AU  - Dudley ME
AD  - Surgery Branch, National Cancer Institute, NIH, CRC 3-3940, 10 Center Dr MSC 
      1201, Bethesda MD 20892-1202, USA.
FAU - Wunderlich, John R
AU  - Wunderlich JR
FAU - Yang, James C
AU  - Yang JC
FAU - Sherry, Richard M
AU  - Sherry RM
FAU - Topalian, Suzanne L
AU  - Topalian SL
FAU - Restifo, Nicholas P
AU  - Restifo NP
FAU - Royal, Richard E
AU  - Royal RE
FAU - Kammula, Udai
AU  - Kammula U
FAU - White, Don E
AU  - White DE
FAU - Mavroukakis, Sharon A
AU  - Mavroukakis SA
FAU - Rogers, Linda J
AU  - Rogers LJ
FAU - Gracia, Gerald J
AU  - Gracia GJ
FAU - Jones, Stephanie A
AU  - Jones SA
FAU - Mangiameli, David P
AU  - Mangiameli DP
FAU - Pelletier, Michelle M
AU  - Pelletier MM
FAU - Gea-Banacloche, Juan
AU  - Gea-Banacloche J
FAU - Robinson, Michael R
AU  - Robinson MR
FAU - Berman, David M
AU  - Berman DM
FAU - Filie, Armando C
AU  - Filie AC
FAU - Abati, Andrea
AU  - Abati A
FAU - Rosenberg, Steven A
AU  - Rosenberg SA
LA  - eng
GR  - Z01 BC010763-01/Intramural NIH HHS/United States
GR  - Z99 CA999999/Intramural NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Interleukin-2)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - FA2DM6879K (Vidarabine)
RN  - P2K93U8740 (fludarabine)
SB  - IM
MH  - Adolescent
MH  - *Adoptive Transfer
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Child
MH  - Cyclophosphamide/administration & dosage
MH  - Disease Progression
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Interleukin-2/pharmacology
MH  - *Lymphocytes, Tumor-Infiltrating
MH  - Male
MH  - Melanoma/*immunology/*therapy
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Skin Neoplasms/*immunology/*therapy
MH  - Treatment Outcome
MH  - Vidarabine/administration & dosage/*analogs & derivatives
PMC - PMC1475951
MID - NIHMS10166
EDAT- 2005/04/01 09:00
MHDA- 2005/04/22 09:00
PMCR- 2008/01/27
CRDT- 2005/04/01 09:00
PHST- 2005/04/01 09:00 [pubmed]
PHST- 2005/04/22 09:00 [medline]
PHST- 2005/04/01 09:00 [entrez]
PHST- 2008/01/27 00:00 [pmc-release]
AID - 23/10/2346 [pii]
AID - 10.1200/JCO.2005.00.240 [doi]
PST - ppublish
SO  - J Clin Oncol. 2005 Apr 1;23(10):2346-57. doi: 10.1200/JCO.2005.00.240.