Sequence of Cyclophosphamide (Cy) and Total Body Irradiation (TBI) Prior to Hematopoietic Cell Transplant (HCT) for Patients with Acute Leukemia: Impact upon Complications and Patient Outcome

Abstract Abstract 4552 Background: 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. Patients and Methods: 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. Results: 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. Conclusion: 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. Disclosures: No relevant conflicts of interest to declare.

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Donor Telomere Length and Outcomes after Allogeneic Unrelated Hematopoietic Cell Transplant in Patients with Acute Leukemia

Blood ◽

10.1182/blood.v128.22.520.520 ◽

2016 ◽

Vol 128 (22) ◽

pp. 520-520 ◽

Cited By ~ 1

Author(s):

Shahinaz M. Gadalla ◽

Tao Wang ◽

David Loftus ◽

Lyssa Friedman ◽

Casey Dagnall ◽

...

Keyword(s):

Acute Leukemia ◽

Telomere Length ◽

Cancer Genomics ◽

Disease Free Survival ◽

Hematopoietic Cell ◽

Unrelated Donor ◽

Cell Transplant ◽

Hematopoietic Cell Transplant ◽

Specific Distribution ◽

Neutrophil Engraftment

Abstract Introduction. A recent study showed that receiving a hematopoietic cell transplant (HCT) from donors with long leukocyte relative telomere length (RTL) was associated with improved survival in patients with severe aplastic anemia who primarily received bone marrow grafts at age <40 years. Here, we tested the effect of donor RTL on post-HCT outcomes in a large cohort of patients with acute leukemia. Methods. From the Center for International Blood and Marrow Transplant Research (CIBMTR®) database, we identified 1,097 patients who received unrelated HCT for acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) and fulfilled the following criteria: 1) HCT between 2004 and 2012, 2) available pre-HCT blood sample for the donor, 3) 8/8 HLA matching, and 3) myeloablative conditioning. We used qPCR to measure RTL; 1084 samples completed testing (597 measured at Telomere Diagnostics, Inc. and 487 at the Cancer Genomics Research Laboratory, NCI). Telomere Diagnostics samples were randomly divided into discovery (n=300) and validation (n=297) cohorts; the NCI samples served as a 2nd validation cohort (N=500). Cox proportional hazard models were used for statistical analyses. All analyses were adjusted for donor age together with clinical factors that met statistical inclusion criteria in a multivariate model. Donor RTL was categorized into short (≤25th percentile based on cohort-specific distribution), or long otherwise. Follow-up ended in November 2014. Results. All patient demographics, disease- and HCT-related characteristics were similar in the discovery, 1st, and 2nd validation cohorts with the exception of graft source (peripheral blood stem cells in 67%, 60%, and 70%, respectively, p=0.008), and year of HCT (0%, 0%, and 37% between 2008-2012, respectively, p<0.001). Results from the discovery cohort suggested that long donor RTL may be associated with: 1) improved overall survival (HR=0.73, 95% CI=0.52-1.03, p=0.08), and disease-free survival (HR=0.73, 95% CI=0.52-1.03, p=0.07); 2) higher probability of neutrophil engraftment (HR=1.3, 95% CI=0.99-1.71, p=0.06), and 3) decreased risk of relapse (HR=0.61, 95% CI=0.38-1.00, p=0.05) and acute graft-versus-host disease II-IV (HR=0.68, 95% CI=0.46-1.0, p=0.05). However, none of these results were replicated in the two validation cohorts with the exception of a higher probability of neutrophil engraftment observed in the 2nd (HR=1.24, 95% CI=1.0-1.54, p=0.05), but not the 1st validation (HR=0.84, 95% CI=0.63-1.11, p=0.21). All three cohorts were combined for a final exploratory analysis and no associations (all p>0.3) were found between donor telomere length and any outcomes. Conclusions. Donor telomere length is not associated with outcomes in unrelated donor HCT for patients with acute leukemia. Table. Impact of donor RTL comparing the three longest quartiles to the shortest quartile. Table. Impact of donor RTL comparing the three longest quartiles to the shortest quartile. Disclosures Loftus: Telomere Diagnostics, Inc.: Consultancy. Friedman:Telomere Diagnostics, Inc.: Consultancy. Buturovic:Clinical Persona: Consultancy. Blauwkamp:Telomere Diagnostics, Inc.: Employment. Shelton:Telomere Diagnostics, Inc.: Employment.

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