scholarly journals Cumulative incidence of subsequent malignancy after allo-HCT conditioned with or without low-dose total body irradiation

Author(s):  
Lina Nunez ◽  
Tasnima Abedin ◽  
Syed Ali Naqvi ◽  
Hua Shen ◽  
Ahsan Chaudhry ◽  
...  

Subsequent malignancies (SM) present a significant burden of morbidity and are a common cause of late mortality in survivors of allogeneic HCT (hematopoietic cell transplant). Previous studies have described total body irradiation (TBI) as a risk factor for the development of SM in allo-HCT survivors. However, most studies of the association between TBI and SM have examined high dose TBI regimes (typically ≥600cGy) and thus little is known about the association between low dose TBI regimens and risk of SM. Thus, we set out to compare the cumulative incidence of SM in Albertan patients who received busulfan/fludarabine alone versus busulfan/fludarabine plus 400 cGy TBI. Of 674 included patients, 49 patients developed a total of 56 malignancies at a median of 5.9 years post-transplant. The cumulative incidence of SM at 15 years post-HCT in the entire cohort was 11.5% (95% CI 8.5-15.6%): 13.4% (95% CI 9.1-19.3%) in the no-TBI group and 10.8% (95% CI 6.6-17.4%) in the TBI group. In the multivariable model, TBI was not associated with SM, while number of pre-HCT cycles of chemotherapy was. The standardized incidence ratio for the entire cohort, as compared to the age, sex and calendar-year matched general population was 1.74. Allo-HCT conditioning that includes low dose TBI does not appear to increase risk of SM as compared to chemotherapy-alone conditioning.

2009 ◽  
Vol 27 (2) ◽  
pp. 256-263 ◽  
Author(s):  
Celso A. Rodrigues ◽  
Guillermo Sanz ◽  
Claudio G. Brunstein ◽  
Jaime Sanz ◽  
John E. Wagner ◽  
...  

PurposeTo determine risk factors of umbilical cord blood transplantation (UCBT) for patients with lymphoid malignancies.Patients and MethodsWe evaluated 104 adult patients (median age, 41 years) who underwent unrelated donor UCBT for lymphoid malignancies. UCB grafts were two-antigen human leukocyte antigen–mismatched in 68%, and were composed of one (n = 78) or two (n = 26) units. Diagnoses were non-Hodgkin's lymphoma (NHL, n = 61), Hodgkin's lymphoma (HL, n = 29), and chronic lymphocytic leukemia (CLL, n = 14), with 87% having advanced disease and 60% having experienced failure with a prior autologous transplant. Sixty-four percent of patients received a reduced-intensity conditioning regimen and 46% low-dose total-body irradiation (TBI). Median follow-up was 18 months.ResultsCumulative incidence of neutrophil engraftment was 84% by day 60, with greater engraftment in recipients of higher CD34+kg/cell dose (P = .0004). CI of non–relapse-related mortality (NRM) was 28% at 1 year, with a lower risk in patients treated with low-dose total-body irradiation (TBI; P = .03). Cumulative incidence of relapse or progression was 31% at 1 year, with a lower risk in recipients of double-unit UCBT (P = .03). The probability of progression-free survival (PFS) was 40% at 1 year, with improved survival in those with chemosensitive disease (49% v 34%; P = .03), who received conditioning regimens containing low-dose TBI (60% v 23%; P = .001), and higher nucleated cell dose (49% v 21%; P = .009).ConclusionUCBT is a viable treatment for adults with advanced lymphoid malignancies. Chemosensitive disease, use of low-dose TBI, and higher cell dose were factors associated with significantly better outcome.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4552-4552
Author(s):  
Cara L. Toretta ◽  
Andrzej Niemierko ◽  
Erin Coughlin ◽  
Steven L. McAfee ◽  
Bimalangshu R. Dey ◽  
...  

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.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5105-5105
Author(s):  
Hongwei Liu ◽  
Matthew Seftel ◽  
Allain Demers ◽  
Zoann Nugent ◽  
Garry Schroeder ◽  
...  

Abstract OBJECTIVES: The optimum high dose preparative regimen for non-Hodgkin lymphoma (NHL) patients undergoing autologous stem cell transplantation (ASCT) is unknown. We compared the radiation-based regimen of cyclophosphamide, etoposide and 12 Gy total body irradiation (CY/E/TBI) to carmustine, etoposide, cytarabine and melphalan (BEAM) in NHL patients who received ASCT. We investigated acute and long-term toxicities, disease free survival (DFS), overall survival (OS) of these two regimens. METHODS: A historical cohort study was performed at a provincial cancer centre. Cause specific survival was determined with the Kaplan-Meier method. Survival between groups was compared using the log-rank test. RESULTS: From Mar-1991 to Sep-2005, 79 patients received CY/E/TBI (n=32) or BEAM (n=47). Histology was indolent in 30 and aggressive in 49 patients. Cell source was bone marrow in six and 73 received peripheral blood progenitor cells. Prior to ASCT, ten patients were in complete remission, 47 had chemo-sensitive disease and 22 had chemo-resistant disease. There were only two cases of interstitial pneumonitis, with one in each preparative regimen group. There were six transplant related deaths; two in the BEAM group and four were in TBI group. The TBI based group has a higher mean mucosits score (p=0.03). Five year DFS was 47% and 51% in the TBI and BEAM groups, respectively (p=0.41). Five year OS was 50% and 64% for the TBI and BEAM based groups (p=0.07). Multivariate analyzes revealed that patients with more advanced disease and raised LDH at ASCT independently predicted inferior DFS. There was one case of acute myeloid leukemia and two of prostate cancer, all of whom were in the TBI group. CONCLUSIONS: In this study, a 12 Gy TBI-based regimen resulted in a similar DFS but a trend toward poorer OS and higher second malignancies than a BEAM-based regimen. However, there did not appear to be excess pulmonary acute toxicities in the TBI based group.


Blood ◽  
2005 ◽  
Vol 105 (3) ◽  
pp. 1010-1015 ◽  
Author(s):  
Mikko O. Laukkanen ◽  
Ken Kuramoto ◽  
Boris Calmels ◽  
Masaaki Takatoku ◽  
Christof von Kalle ◽  
...  

Abstract Due to high frequency of side effects caused by high-dose total body irradiation (TBI) the nonmyeloablative regimen together with cytotoxic agents is currently used especially for elderly patients. However, immediate and long-term effects of low-dose irradiation used in allogeneic transplantation on stem cells is less well known. We have studied the effect of low-dose 3 Gy TBI on the number of hematopoietic stem cell (HSC) clones contributing simultaneously to granulocyte production in rhesus macaque. The number of clones after 3 Gy TBI decreased markedly by 2 to 3 weeks after 3 Gy TBI, followed by a period of clonal instability, and recovery to almost pre–3 Gy TBI clonal diversity. The clones accounting for this recovery contributed before 3 Gy TBI, suggesting the profound initial impact of TBI was on a pool of progenitor cells, whereas most of the more primitive HSCs remained unaffected and were able to again contribute to hematopoiesis after recovery. Clonal fluctuation may indirectly suggest the presence of short-term/long-term HSC populations in rhesus macaque bone marrow as reported in a mouse model. The results indicate that even low-dose irradiation affects hematopoietic clonal dynamics and have implications for design of conditioning regimens for transplantation purposes.


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