High-Dose Chemotherapy and Autologous Hematopoietic Progenitor Cell Transplantation (AHCT) for Non-Hodgkin’s Lymphoma (NHL) in Patients over 65 Years of Age.
Authors: Hosing Chitra , Saliba Rima M. , Okoroji Grace-Julia , Popat Uday , Couriel Daniel , Kebriaei Partow , Ali Tanveer , De Lima Marcos , Qazilbash Muzaffar , Anderlini Paolo , Giralt Sergio , Champlin Richard E. , Khouri Issa 
Published: October 2019

High-dose chemotherapy followed by AHCT is the treatment of choice for relapsed NHL. Often this therapy is not offered to patients over 65 yrs of age because of concerns regarding their ability to tolerate “aggressive therapy”. We present a retrospective analysis of 99 consecutive pts. who underwent AHCT for NHL at our institution from 6/96–3/06.

RESULTS: Median age at AHCT was 68 yrs (range, 65–83). Seventy percent were males. Most common histologies were DLCL (55%), MCL (15%), and FL grades 1–3 (15%). Median number of chemoregimens administered prior to AHCT were 2 (range, 1–6). Median IPI score at AHCT was 1 (range, 0–4). Majority of patients (99%) had a ECOG PS score of < 2 prior to AHCT. Forty-four percent pts were in CR/CRu, 45% were in PR, and 11% had PD/SD. The preparative regimen comprised of BEAM (35%), BEAM/rituximab (53%), and Cy/TBI +/− rituximab (10%). Median hospital stay was 23 days (range, 6–85) for AHCT with 38% requiring readmission within the first 100 days. Source of progenitor cells was HPC-A in 89%. Median CD34+ cell dose infused/kg was 4.4 x 106 (0.1–32.2). All patients engrafted. Median time to reach ANC ≥ 500/mm3 was 10 days (range 7–47). Ten patients never achieved a platelet (PLT) count of 20,000/mm3. For the remaining 88 pts., median time to reach PLT ≥ 20,000/mm3 was 13 days (range, 6–375). Median number of PRBC units transfused were 4 (range, 0–50) and median number of PLT transfusions required were 4 (range, 0–35). Grade 3–5 RRT toxicity is summarized in Table.

Table *RRT Grades 3–5 Age years (No.) 65–69 (58 pts) 70–75 (34 pts) > 75 (8 pts) *CTCAE ver 3.0 Toxicity Grade 3/4/5 3/4/5 3/4/5 Pulmonary (pnemonitis) 1/1/0 0/0/1 0/0/1 GI (diarrhea) 6/0/0 2/0/0 0/0/0 GI (mucositis/stomatitis) 6/0/0 0/0/0 1/0/0 GI (nausea) 0/0/0 0/0/0 1/0/0 Neurologic (confusion) 1/0/0 1/0/0 0/0/0 GU (inc creatinine) 1/0/0 2/0/0 0/0/0 Hepatic 1/1/0 1/0/0 0/0/0 Cardiovascular 3/0/0 1/0/0 1/1/0 Allergy (BCNU) 1/0/0 0/0/0 0/0/0 Skin rash 1/0/0 0/0/0 0/0/0 Fatigue/Bone pain 1/0/0 0/0/0 1/0/0

Cumulative TRM was 12 % (95% CI 6–22) at 3 yrs. Median follow-up among survivors is 26 mths (range, 1–115). OS at 3 yrs was 61% (95% CI 49–71) for the entire cohort. At 3 yrs the DFS was 48% (95% CI 33–61), 68% (95% CI 36–87), and 63% (95% CI 22–87) for DLCL, MCL and FL respectively. On univariate analysis IPI > 1, LDH > normal, and SD/PD at the time of AHCT were predictors of worse OS. Disease status at transplant and LDH > normal remained significant predictors for OS on multivariate analysis. Age, gender, histology, number of prior chemoregimens, time from diagnosis to AHCT, and conditioning regimen were not significant predictors of OS. Cause of death was disease progression/relapse in 60%. Eight patients developed sMDS/AML after AHCT.

CONCLUSIONS: Patients over 65 yrs of age can undergo AHCT with acceptable toxicity and should be considered transplant candidates if they have chemosensitive disease and an IPI score of ≤ 1 at the time of AHCT.