A Jain

A Zeevi

A.S Rao

Barber

C.A Vivas

Ciancio

Corry

E.A Gray

Fontes

Garcia-Morales

I Dvorchik

J McCauley

J McMichael

J.J Fung

M Valenti

M.L Jordan

McDaniel

Miller

Monaco

P Randhawa

Quesenberry

R Shapiro

R.J Corry

Shapiro

Spitzer

T.E Starzl

V.P Scantlebury

English

PubMed

Crossref

Transplantation Proceedings

Kidney transplantation with bone marrow augmentation: five-year outcomes

Shapiro, R

Rao, AS

Corry, RJ

Valenti, M

Zeevi, A

Jordan, ML

Scantlebury, VP

Vivas, CA

Jain, A

McCauley, J

Randhawa, P

Gray, EA

Dvorchik, I

McMichael, J

Fung, JJ

Starzl, TE

Name not available

Kidney transplantation with bone marrow augmentation: five-year outcome

D-Scholarship@Pitt

ELSEVIER Kidney Transplantation With Bone Marrow Augmentation: Five-Year Outcomes R. Shapiro, AS. Rao, R.J. Corry, M. Valenti, A Zeevi, M.L. Jordan, V.P. Scantlebury, C.A. Vivas, A Jain, J. McCauley, P. Randhawa, E.A. Gray, I. Dvorchik, J. McMichael, J.J. Fung, and T.E. Starzl BONE marrow augmentation in renal transplant recip-ients has been performed in a small number of centers, in an attempt to augment chimerism and/or provide donor-specific immunomodulatiQn. I- 14 In this report, we present our experience with bone marrow augmentation in renal transplantation over the past 7 years. PATIENT AND METHODS Between December l4, 1992, and January 1, 2000, 124 kidneylbone marrow transplants were performed. There were 51 (41%) cadav-eric kidney, 59 (48%) kidney/pancreas, 8 (6%) kidney/islet, and 6 (5%) living-related kidney recipients. The mean recipient age was 40.4 :!: 10.5 years. The dosage of unmodified bone marrow was 3 to 5 x 10" cells/kg, given either as a single infusion (n = 86; 69%), or as multiple infusions (n = 38,31%).'5 The mean donor age was 33.0 :':: 15.5 years, and the mean cold ischemia time was 17.8 ::': 9.6 hours. The mean number of HLA matches and mismatches was 1.9 ::': 1.3 and 3.8 ;!: 1.3, respectively. Eighty patients who could have undergone kidneylbone marrow transplantation but did not because of lack of bone marrow availability were studied as controls. There were 45 (56%) cadaveric kidney, 32 (40%) kidney! pancreas, 2 (3%) kidney/islet, and 1 (1%) living-related kidney recipients in the control group. This was not a randomized trial; the availability of donor bone marrow was sporadic, and the total case material accounted for only about 10% of the transplants per-formed during this time period. The mean recipient age was 43.8 ::': 10.8 years. The mean donor age was 36.7 ::': 17.3 years, and the mean cold ischemia time was 21.9 ::': 10.0 hours. The mean number of HLA matches and mismatches was 2.2 ::': 1.5 and 3.5 ::': 1.6, respectively. Immunosuppression was with tacrolimus-based immunosuppres-sion, as previously described 6 . 16 Antibody induction was not given, nor was radiation or cytoreduction therapy. The bone marrow and control protocols were submitted to and approved by the fnstitutiona~ Review Board of the University of Pittsburgh. RESULTS The mean follow up was 36.4 :':: 23.2 months. In the K/BM group, the 1- and 5-year actuarial patient survival was 98% and 85%, and the 1- and 5-year actuarial graft survival was 97% and 76%. In the control group, the 1- and 5-year actuarial patient survival was 97% and 85%, and the 1- and 5-year actuarial graft survival was 93% arid 71 % (P = NS). 0041-1345/01/$-see front matter PII 80041-1345(00)02461-1 1134 The mean serum creatinine in the K/BM group was 1.6 ::':: .6 mgidL; in the control group, it was 1.6 ::':: 1.0 mgidL. The incidences of rejection and steroid-resistant rejec-tion in the K/BM group were 60% and 6%; in the control group, they were 69% and 10%, respectively. An analysis of the incidence of chronic allograft nephropathy suggested a relative risk of .71 in the K/BM group relative to the control group, with a 95% confidence interval of 0.46 to 1.09. Although this difference did not achieve statistical signifi-cance, it appeared to be progressive over time. The incidence .of symptomatic cytomegalovirus was 17% in the K/BM group and 18% in the control group. The incidence of posttransplant lymphoproliferative disorders (PTLD) was 3% in the bone marrow group and 0% in the control group (P = NS). The initial and final incidences of posttransplant diabetes mellitus were 21 % and 11 % in the bone marrow group, and 22% and 11% in the control group. Of patients who had kept their renal allografts for 1 year or more, 65% of K/BM patients and 61 % of the control patients were withdrawn from steroids. Chimerism, by PCR, was seen in 92% of the K/BM group and 64% of the.control group. The incidence of decreal>ing donor-specific reactivity was 45% in the K/BM group, and 32% in the control group. Graft-versus-host disease was not seen in any patient. DISCUSSION This analysis confirms earlier reports suggesting that bone marrow augmentation in renal transplant recipients is as-sociated with reasonable patient and graft survival,5.6.7.9.lo and extends these findings, with 5-year actuaria) patient and graft survival rates of 85% and 76%, respectively. As in previous analyses, no significant improvement was noted i.n graft survival, when compared with control patients not receiving bone marrow.6 •7,10 However, there is a suggestion that bone marrow augmentation had some immunomodu-From the Thomas E. Starzl Transplantation Institute, Depart-ment of Surgery, University of Pittsburgh, Pittsburgh, Pennsyl-vania. Address reprint requests to Dr R. Shapiro, 3601 5th Ave, 4th Floor, Pittsburgh, PA 15213. © 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 33, 1134-1135 (2001) ___ ------nlmIHmmll-----------BONE MARROW AUGMENTATION latory effect, with a trend toward a progressive decrease in the incidence of chronic allograft nephropathy. This obser-vation has also been made by the Miami group.8,II-J3 Also .noted was a slight increase in the incidence of PTLD. Although not statistically significant, this observation is still worrisome and suggests that it may be necessary to main-tain bone marrow augmented renal transplant recipients on somewhat lower levels of chronic immunosuppression. In our report on the effect of bone marrow augmentation - in the simultaneous pancreas/kidney patients, there ap-peared to be a more significant effect of bone marrow on reducing pancreatic graft loss to rejection. 17 Perhaps this is related in some way to the possible additional effect of transplantation of mesenteric and periduodenal lymph nodes and other lymphatic tissues in the p'!ncreas-duodenal transp Ian t. Important questions that remain include the impact of chimerism itself on patient and graft survival, and the impact of multiple bone marrow infusions compared to a single infusion. These analyses remain ongoing. In conclusion, bone marrow augmentation appears to be associated with reasonable patient and graft survival, rou-tine augmentation of chimerism, some increase in the percentage of patients with decreasing donor-specific reac-tivity, and a trend toward less chronic allograft nephropa-thy. REFERENCES 1. Monaco AP, Clark A W, Wood ML, et al: Surgery 79:384, 1976 1135 2. Monaco AP, Wood ML, Maki T, et al: Transplant Proe 17:1312, 1985 3. Barber WH, Mankin lA, Laskow DA, et al: Transplantation 51:70, 1991 4. McDaniel DO, Naftilan J, Hulvey K, et al: Transplantation 57 :852, 1994 5. Fontes P, Rao A, Demetris AJ, et al: Lancet 344:151, 1994 6. Shapiro R, Rao AS, Fontes P, et al: Transplantation 59:306, 1995 7. Shapiro R, Rao AS, Fontes P, et al: Transplantation 60:1421, 1995 8. Garcia-Morales R, Carreno M, Mathew l, et al: J Clin Invest 99:1118,1997 -9. Rao AS, Shapiro R, Corry R, et al: Transplant Proc 30:1367, 1998 10. Shapiro R, Starzl TE: Transplant Proc 30:1:371, 1998 11. Ciancio G, Garcia-Morales R, Burke GW, et al: Transplant Proc 30:1365, 1998 12. Ciancio G, Garcia-Morales R, Burke GW, et al: Transplant Proc 31:679, 1999 13. Miller J, Mathew J, Garcia-Morales R, et al: Transplantation 68: 1 079, 1999 14. Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al: Transplan-tation 68:480, 1999 15. Quesenberry PJ, Ramshaw H, erittenden RB, et al: Blood Cells 20:348, 1994 16. Shapiro R, Jordan ML, Scantlebury YP, et al: Transplanta-tion 59:485, 1995 17. Corry R, Chakrabarti P, Shapiro R, et al: Ann Surg 230:372, 1999 ~ I I ----------------------------------....... 

Kidney transplantation with bone marrow augmentation: Five-year outcomes

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Kidney transplantation with bone marrow augmentation: Five-year outcomes

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