reduced-intensity stem cell transplantation in two cases of metastatic renal cell carcinoma

1
International Journal of Urology (2003) 10, 615 Blackwell Science, LtdOxford, UKIJUInternational Journal of Urology0919-81722003 Blackwell Publishing Asia Pty LtdNovember 20031011615Editorial Comment RIST for metastatic RCCY Tomita Editorial Comment Reduced-intensity stem cell transplantation in two cases of metastatic renal cell carcinoma There have been few effective treatment options for cytokine-refractory renal cell carcinoma (RCC). A report of non-myeloablative allogeneic stem cell trans- plantation, which has recently been more popularly termed as reduced intensity stem cell transplantation (RIST), to RCC patients by Childs et al. in the New England Journal of Medicine in 1999 created a sensa- tion. Nine of 18 cytokine-refractory cases experienced tumor regression, which seemed to be a durable response in many of the cases. 1 Other institutions have revealed similar promising results. 2,3 However, in another study of eight patients, none of the patients showed response. 4 In the present issue of the Interna- tional Journal of Urology Aoyama et al. report two cases of RCC treated with RIST. The two patients revealed progression of disease besides achieving com- plete chimera within 100 days after the transplantation. However, in one patient, transient pulmonary regression was observed along with Graft-versus-host disease (GVHD). In Japan, at the end of 2002, 22 patients had been treated with RIST at eight institutions. The best responses of this series were three partial responses, nine stable disease and three progressive disease (pers. comm.). Discrepancy of these effects may be the result of two factors: varied treatment protocol and patient selection. Each treatment protocol, however, achieved complete chimera with several exceptional cases. Among the reported cases, tumor regression was experienced more frequently concomitant with GVHD as reported by Aoyama et al. in the present issue of this journal. Pres- ence or absence of GVHD, therefore, might affect antitumor response relevant to conditioning and admin- istration of immunosuppressants to control GVHD. Balance between tumor cell proliferation and lysis caused by immune cells originated from allogeneic blood stem cells determine clinical responses, i.e. change of size of metastatic lesions. It is conceivable that tumors with high proliferation activity, such as sar- comatoid RCC, may overcome immune cell attack resulting in tumor progression despite the presence of graft-versus-tumor reaction. Careful patient selection and standardization of a standard protocol would con- tribute to an increased response rate for advanced RCC. Yoshihiko Tomita MD Department of Urology Yamagata University School of Medicine Yamagata, Japan References 1 Childs R, Chemoff A, Contentin N et al. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogenic peripheral-blood stem-cell transplantation. N. Engl. J. Med. 2000; 043: 750–8. 2 Rini BI, Zimmerman T, Stadler WM, Gajewski TF, Vogelzang NJ. Allogenic transplantation of renal cell cancer after nonmyeloablative chemotherapy: feasibility, engraftment, and clinical results. J. Clin. Oncol. 2002; 20: 2017–24. 3 Bregni M, Dodero A, Peccatori J et al. Nonmyeloabla- tive conditioning, followed by hematopoietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer. Blood. 2002; 99: 4234–6. 4 Pedrazzoli P, Da Prada GA, Giorgiani G et al. Alloge- neic blood stem cell transplantation after a reduced- intensity, preparative regimen: a pilot study in patients with refractory malignancies. Cancer. 2002; 94: 2409– 15.

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Page 1: Reduced-intensity stem cell transplantation in two cases of metastatic renal cell carcinoma

International Journal of Urology

(2003)

10,

615

Blackwell Science, LtdOxford, UKIJUInternational Journal of Urology0919-81722003 Blackwell Publishing Asia Pty LtdNovember 20031011615Editorial Comment

RIST for metastatic RCCY Tomita

Editorial Comment

Reduced-intensity stem cell transplantation in two cases of metastatic renal cell carcinoma

There have been few effective treatment options forcytokine-refractory renal cell carcinoma (RCC). Areport of non-myeloablative allogeneic stem cell trans-plantation, which has recently been more popularlytermed as reduced intensity stem cell transplantation(RIST), to RCC patients by Childs

et al

. in the

NewEngland Journal of Medicine

in 1999 created a sensa-tion. Nine of 18 cytokine-refractory cases experiencedtumor regression, which seemed to be a durableresponse in many of the cases.

1

Other institutions haverevealed similar promising results.

2,3

However, inanother study of eight patients, none of the patientsshowed response.

4

In the present issue of the

Interna-tional Journal of Urology

Aoyama

et al

. report twocases of RCC treated with RIST. The two patientsrevealed progression of disease besides achieving com-plete chimera within 100 days after the transplantation.However, in one patient, transient pulmonary regressionwas observed along with Graft-versus-host disease(GVHD). In Japan, at the end of 2002, 22 patients hadbeen treated with RIST at eight institutions. The bestresponses of this series were three partial responses,nine stable disease and three progressive disease (pers.comm.).

Discrepancy of these effects may be the result of twofactors: varied treatment protocol and patient selection.Each treatment protocol, however, achieved completechimera with several exceptional cases. Among thereported cases, tumor regression was experienced morefrequently concomitant with GVHD as reported byAoyama

et al.

in the present issue of this journal. Pres-ence or absence of GVHD, therefore, might affectantitumor response relevant to conditioning and admin-istration of immunosuppressants to control GVHD.Balance between tumor cell proliferation and lysis

caused by immune cells originated from allogeneicblood stem cells determine clinical responses, i.e.change of size of metastatic lesions. It is conceivablethat tumors with high proliferation activity, such as sar-comatoid RCC, may overcome immune cell attackresulting in tumor progression despite the presence ofgraft-versus-tumor reaction. Careful patient selectionand standardization of a standard protocol would con-tribute to an increased response rate for advancedRCC.

Yoshihiko Tomita

MD

Department of UrologyYamagata University School of Medicine

Yamagata, Japan

References

1 Childs R, Chemoff A, Contentin N

et al.

Regression ofmetastatic renal-cell carcinoma after nonmyeloablativeallogenic peripheral-blood stem-cell transplantation.

N.Engl. J. Med.

2000;

043

: 750–8.2 Rini BI, Zimmerman T, Stadler WM, Gajewski TF,

Vogelzang NJ. Allogenic transplantation of renal cellcancer after nonmyeloablative chemotherapy: feasibility,engraftment, and clinical results.

J. Clin. Oncol.

2002;

20

: 2017–24.3 Bregni M, Dodero A, Peccatori J

et al.

Nonmyeloabla-tive conditioning, followed by hematopoietic cellallografting and donor lymphocyte infusions forpatients with metastatic renal and breast cancer.

Blood.

2002;

99

: 4234–6.4 Pedrazzoli P, Da Prada GA, Giorgiani G

et al.

Alloge-neic blood stem cell transplantation after a reduced-intensity, preparative regimen: a pilot study in patientswith refractory malignancies.

Cancer.

2002;

94

: 2409–15.