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. 2015 Sep 4:8:102.
doi: 10.1186/s13045-015-0201-x.

Clinical significance of high-dose cytarabine added to cyclophosphamide/total-body irradiation in bone marrow or peripheral blood stem cell transplantation for myeloid malignancy

Yasuyuki Arai  1 , Kazunari Aoki  2 , June Takeda  3 , Tadakazu Kondo  4 , Tetsuya Eto  5 , Shuichi Ota  6 , Hisako Hashimoto  7 , Takahiro Fukuda  8 , Yukiyasu Ozawa  9 , Yoshinobu Kanda  10 , Chiaki Kato  11 , Mineo Kurokawa  12 , Koji Iwato  13 , Makoto Onizuka  14 , Tatsuo Ichinohe  15 , Yoshiko Atsuta  16   17 , Akiyoshi Takami  18 ; AML and MDS Working Group of Japan Society for Hematopoietic Cell Transplantation
Affiliations

Clinical significance of high-dose cytarabine added to cyclophosphamide/total-body irradiation in bone marrow or peripheral blood stem cell transplantation for myeloid malignancy

Yasuyuki Arai et al. J Hematol Oncol. .

Abstract

Background: Addition of high-dose cytarabine (HDCA) to the conventional cyclophosphamide/total-body irradiation (CY/TBI) regimen significantly improved prognosis after cord blood transplantation (CBT) for adult acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The efficacy of HDCA in bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT), however, has not yet been elucidated.

Findings: We conducted a cohort study to compare the prognosis of HDCA/CY/TBI (N = 435) and CY/TBI (N = 1667) in BMT/PBSCT for AML/MDS using a Japanese transplant registry database. The median age was 38 years, and 86.0% of the patients had AML. Unrelated donors comprised 54.6%, and 63.9% of donors were human leukocyte antigen (HLA)-matched. Overall survival (OS) was not improved in the HDCA/CY/TBI group (adjusted hazard ratio (HR), 1.14; p = 0.13). Neutrophil engraftment was inferior (HR, 0.80; p < 0.01), and the incidence of hemorrhagic cystitis and thrombotic microangiopathy increased in HDCA/CY/TBI (HR, 1.47 and 1.60; p = 0.06 and 0.04, respectively), leading to significantly higher non-relapse mortality (NRM; HR, 1.48; p < 0.01). Post-transplant relapse and tumor-related mortality were not suppressed by the addition of HDCA.

Conclusions: This study indicated the inefficacy of HDCA/CY/TBI in BMT/PBSCT for AML/MDS. Our results should be validated in large-scale prospective studies.

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Figures

Fig. 1
Fig. 1
Prognosis after HCT in each group of the conditioning regimen. a OS was calculated with the Kaplan-Meier method in each group of HDCA/CY/TBI and CY/TBI. HR for overall mortality of HDCA/CY/TBI compared to CY/TBI was calculated by Cox proportional hazards model after being adjusted for confounding factors such as patient sex, age, PS, CMV sero-status, diagnosis, disease risk, days from diagnosis to HCT, HLA mismatch, sex mismatch, and year of HCT. b Tumor-related mortality, defined as death without remission or after relapse, was calculated using Gray’s method considering therapy-related death as a competing risk. HR was calculated by using Fine-Gray proportional hazards model adjusted by the confounding factors mentioned above. c NRM was calculated using Gray’s method considering relapse as a competing risk. HR was also calculated using the same model
Fig. 2
Fig. 2
Clinical courses after HCT in each group of CY/TBI and HDCA/CY/TBI. The cumulative incidence of major clinical events after HCT, such as engraftment, GVHD, infection, and other acute phase complications are summarized. In each event, adjusted HRs in the HDCA/CY/TBI group were analyzed in comparison with the CY/TBI group. Dots indicate HRs, and bars indicate 95 % CI ranges
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References

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