Long-Term Outcomes of Myeloablative Hematopoietic Cell Transplantation Using Total Body Irradiation Prior to Systemic Therapy

Myeloablative total body irradiation (TBI) may be incorporated in the condition regimen prior to hematopoietic cell transplant (HCT) for a variety of hematologic malignancies. Recent studies suggest improved patient tolerance and similar overall outcomes when TBI is administered prior to chemotherapy versus after systemic therapy.

We retrospectively reviewed outcomes of adult patients (>18yrs old) who received myeloablative TBI as part of their conditioning regimen at the Massachusetts General Hospital between 1993 and 2012. All patients received TBI prior to chemotherapy; a median dose 13 Gy (range 12–16 Gy) was delivered. Patient characteristics including presenting disease, treatment course, treatment outcome and late-effects of therapy were analyzed.

The study cohort consisted of 116 patients; 55 patients received TBI for non-Hodgkin lymphoma (NHL), 25 for acute lymphoblastic leukemia (ALL), 16 for acute myelogenous leukemia (AML), 5 for chronic myelogenous leukemia (CML), 9 for Hodgkin lymphoma (HL), and 6 for other hematologic disease including MDS, MM, and CLL. Ten patients died of transplant-related mortality. Sixty-three patients underwent allogeneic HCT with a matched-related donor, 53 patients underwent autologous HCT, 5 patients had a tandem HCT, and the remaining patients were divided evenly among umbilical cord, haploidentical, and matched unrelated donor HCT. Twice daily TBI was administered for most patients; 56 cases received TBI three times daily. Cyclophosphamide + TBI (Cy/TBI) was the most commonly used regimen (n=100).

At the time of this report, 56 patients were still alive, with a median followup of 84.7 months (range 0.5–220 months). Median survival for all 116 cases was 67 months; stratified by diagnosis: 112 months NHL, 50 months HL, 69 months ALL, 20 months AML, 17 months CML, and 36 months for other malignancies. Overall survival for the entire cohort was 53% (95% CI = 43 to 62%) and 43% (95% CI = 32 to 53%) at 5- and 10-years, respectively. Progression free or relapse-free survival (P/RFS) was 44% (95% CI = 34 to 54%) and 33% (95% CI = 23 to 43%) at 5- and 10-years, respectively. Patients with ALL had the longest P/RFS (69 months) followed by NHL (42 months). Thirteen patients developed second malignancies; 9 patients developed skin cancer, 2 were diagnosed with other solid tumors, and 2 patients had both skin cancer and another malignancy. Endocrine dysfunction such as hypothyroidism and hypogonadism was documented in 11 patients, 23 patients developed late ocular toxicity. Other late toxicities include pulmonary (14 patients), cardiac (4 patients), and 11 cases of neuropathy. None of these late toxicities were seen in patients with less than 2.5 years of survivorship after transplant.

Similar to other reports, our results show that conditioning regimens that include the use of TBI prior to high-dose chemotherapy have OS and P/RFS that are comparable to other conditioning regimens. Appropriate screening for late toxicities of therapy should begin in the 3rd year of survivorship.

No relevant conflicts of interest to declare.