Person:
Cosimi, A.

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Cosimi

First Name

A.

Name

Cosimi, A.
Author's Publications: search.filters.isAuthorOfPublication.dab9c408-2639-4497-8754-f44353147af0

Search Results

Now showing 1 - 6 of 6
  • Thumbnail Image
    Publication
    Live Donor Partial Hepatectomy for Liver Transplantation: Is There a Learning Curve?
    (Avicenna Organ Transplantation Institute, 2010) Saidi, R. F.; Elias, N.; Ko, D. S.; Kawai, T.; Markmann, J.; Feng, S.; Cosimi, A.; Hertl, M.
    Background: Donor safety is the first priority in living donor liver transplantation (LDLT). Objective: To determine the characteristics and outcome of live liver donors who underwent donor hepatectomy from January, 1997 to May, 2007 at Massachusetts General Hospital. Methods: 30 patients underwent LDLT between January, 1997 and May, 2007 at our institution. Results: The type of graft was the right lobe (segments 5-8) in 14, left lobe (segments 2-4) in 4, and left lateral sector (segments 2 and 3) in 12 patients. The mean donor age was 36 (range: 26-57) years. The mean follow-up was 48 (range: 18-120) months. No deaths occurred. Overall, 8 (26.6%) patients experienced a total of 14 post-operative complications. Donor complications based on graft type were as follows: left lateral sector (16.7%), left lobe (25%), and right lobe (35.7%). The experience was divided into two periods 1997-2001 (n=15) and 2002-2007 (n=15). Overall complications during 2 periods were 40% and 13.3%, respectively (p<0.001). The incidence of grade III complication also significantly decreased; 66.7% vs 33.3% (p<0.01). Conclusion: Partial hepatectomy in living donors has a learning curve which appears to be approximately 15 cases. This learning curve is not restricted to the surgeons performing the procedure but involves all aspects of patient care.
  • Thumbnail Image
    Publication
    Outcomes of Full-Right-Full-Left Split Liver Transplantation in Adults in the USA: A Propensity-Score Matched Analysis
    (Avicenna Organ Transplantation Institute, 2016) Zimmerman, A.; Flahive, J. M.; Hertl, M.; Cosimi, A.; Saidi, R. F.
    Background: Splitting a liver for utilization in adult/pediatric recipients has been shown to decrease mortality on the wait list without increasing the overall risk of long-term graft failure compared to a whole graft. However, splitting a single donor organ for two adult recipients, full-right-full-left split liver transplantation (FRFLSLT), to overcome organ shortage is still considered controversial. Objective: This study assessed the outcome of FRFLSLT comparing full-right (FR) and full-left (FL) with whole liver (WL) allografts in adults (1998–2010) using UNOS standard transplant analysis and research (STAR) file. Methods: Unadjusted allograft and patient survival were estimated using Kaplan-Meier survival curves. Adjusted analyses of survival were conducted controlling for propensity for WL allograft. Results: There were 83,313 cases of WL, 651 FR and 117 FL. Significant differences were evident in the unadjusted cohort between recipients who received FR and FL including donor, cold ischemic time, and days on transplant waiting list. Use of FL allograft resulted in a trend toward lower graft and patient survival compared to WL and FR, which was not statistically significant (p=0.07). In the matched cohort, FL hemiliver allograft had no detrimental effect on the allograft or patient survival after split liver transplantation when compared to FR and WL. Conclusion: After adjusting for donor and recipient characteristics, there was no difference in allograft or patient survival with the use of FL, FR, or WL after liver transplantation in adults. FRFLSLT is a valuable and safe option to expand the donor pool.
  • Thumbnail Image
    Publication
    HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression
    (New England Journal of Medicine (NEJM/MMS), 2008) Kawai, Tatsuo; Cosimi, A.; Spitzer, Thomas; Tolkoff-Rubin, Nina; Suthanthiran, Manikkam; Saidman, Susan; Shaffer, Juanita; Preffer, Frederic; Ding, Ruchuang; Sharma, Vijay; Fishman, Jay; Dey, Bimalangshu; Ko, Dicken; Hertl, Martin; Goes, Nelson B.; Wong, Waichi; Williams, Winfred; Colvin, Robert; Sykes, Megan; Sachs, David
    Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen. Transient chimerism and reversible capillary leak syndrome developed in all recipients. Irreversible humoral rejection occurred in one patient. In the other four recipients, it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation, and renal function has remained stable for 2.0 to 5.3 years since transplantation. The T cells from these four recipients, tested in vitro, showed donor-specific unresponsiveness and in specimens from allograft biopsies, obtained after withdrawal of immunosuppressive therapy, there were high levels of P3 (FOXP3) messenger RNA (mRNA) but not granzyme B mRNA.
  • Thumbnail Image
    Publication
    Acute Renal Endothelial Injury During Marrow Recovery in a Cohort of Combined Kidney and Bone Marrow Allografts
    (Wiley-Blackwell, 2011) Farris, A.B.; Taheri, D.; Kawai, Tatsuo; Fazlollahi, L.; Wong, Wesley; Tolkoff-Rubin, Nina; Spitzer, Thomas; Iafrate, Anthony; Preffer, Frederic; LoCascio, S. A.; Sprangers, B.; Saidman, Susan; Smith, Raymond; Cosimi, A.; Sykes, Megan; Sachs, David; Colvin, Robert
    An idiopathic capillary leak syndrome (“engraftment syndrome”) often occurs in recipients of hematopoietic cells, manifested clinically by transient azotemia and sometimes fever and fluid retention. Here we report the renal pathology in 10 recipients of combined bone marrow and kidney allografts. Nine developed graft dysfunction on day 10–16 and renal biopsies showed marked acute tubular injury, with interstitial edema, hemorrhage and capillary congestion, with little or no interstitial infiltrate (≤10%) and marked glomerular and peritubular capillary (PTC) endothelial injury and loss by electron microscopy. Two had transient arterial endothelial inflammation; and 2 had C4d deposition. The cells in capillaries were primarily CD68+MPO+ mononuclear cells and CD3+CD8+ T cells, the latter with a high proliferative index (Ki67+). B cells (CD20+) and CD4+ T cells were not detectable, and NK cells were rare. XY FISH showed that CD45+ cells in PTCs were of recipient origin. Optimal treatment remains to be defined; two recovered without additional therapy, six were treated with anti-rejection regimens. Except for one patient, who later developed thrombotic microangiopathy and one with acute humoral rejection, all fully recovered within 2–4 weeks. Graft endothelium is the primary target of this process, attributable to as yet obscure mechanisms, arising during leukocyte recovery.
  • Thumbnail Image
    Publication
    Mixed Chimerism, Lymphocyte Recovery, and Evidence for Early Donor-Specific Unresponsiveness in Patients Receiving Combined Kidney and Bone Marrow Transplantation to Induce Tolerance
    (Ovid Technologies (Wolters Kluwer Health), 2010) LoCascio, Samuel A.; Morokata, Tatsuaki; Chittenden, Meredith; Preffer, Frederic; Dombkowski, David M.; Andreola, Giovanna; Crisalli, Kerry; Kawai, Tatsuo; Saidman, Susan; Spitzer, Thomas; Tolkoff-Rubin, Nina; Cosimi, A.; Sachs, David; Sykes, Megan
    Background We have previously reported operational tolerance in patients receiving HLA-mismatched combined kidney and bone marrow transplantation (CKBMT). We now report on transient multilineage hematopoietic chimerism and lymphocyte recovery in five patients receiving a modified CKBMT protocol, and evidence for early donor-specific unresponsiveness in one of these patients. Methods Five patients with end-stage renal disease received CKBMT from HLA-mismatched, haploidentical living related donors following modified non-myeloablative conditioning. Polychromatic flow cytometry (FCM) was used to assess multilineage chimerism where evaluable and lymphocyte recovery post-transplant. Limiting dilution analysis was used to assess helper-T-lymphocyte reactivity to donor antigens. Results Transient multilineage mixed chimerism was observed in all patients but chimerism became undetectable by 2 weeks post-CKBMT. A marked decrease in T and B lymphocyte counts immediately following transplant was followed by gradual recovery. Initially recovering T cells were depleted of CD45RA+/CD45RO− “naïve-like” cells, which have shown strong recovery in two patients and CD4/CD8 ratios increased immediately following transplant but then declined markedly. NK cells were enriched in the peripheral blood of all patients following transplant. For Subject 2, a pre-transplant limiting dilution assay revealed T helper cells recognizing both donor and third-party PBMCs. However, the anti-donor response was completely undetectable by Day 24, while third-party reactivity persisted. Conclusion These results characterize the transient multilineage mixed hematopoietic chimerism and recovery of lymphocyte subsets in patients receiving a modified CKBMT protocol. The observations are relevant to the mechanisms of donor-specific tolerance in this patient group.
  • Thumbnail Image
    Publication
    Tolerance Induction after Organ Transplantation, “Delayed Tolerance,” Via the Mixed Chimerism Approach: Planting Flowers in a Battle Field
    (Landes Bioscience, 2012) Yamada, Yohei; Benichou, Gilles; Cosimi, A.; Kawai, Tatsuo
    We have previously reported that peri-transplant conditioning leads to successful induction of renal allograft tolerance via the mixed chimerism approach in nonhuman primates (NHP) and humans. However, this strategy requires treatments beginning six days prior to transplantation, which limits its relevance only to living donor transplant recipients. To extend the clinical applicability of this approach, we developed a novel regimen “delayed tolerance,” with which the recipient initially undergoes organ transplantation with conventional immunosuppression, followed by conditioning and donor bone marrow transplantation (DBMT) at a later date. This approach might be likened to “planting flowers in a battle field.” That is, the recipient’s immunologic environment after organ transplantation is like a battlefield filled with hostile innate and adaptive immune-responses directed against donor antigeneic specificities. Implanting fragile donor hematopoietic progenitors into this environment and encouraging them to bloom in this vicious field requires special treatments. In our NHP studies recently published in The American Journal of Transplantation, we showed that such “delayed tolerance,” in fact, can be induced in NHP through the mixed chimerism approach, if specific modifications to overcome/avoid donor-specific memory T cell responses are provided. These modifications include adequate depletion of CD8 memory T cells and timing of donor bone marrow administration to minimize levels of pro-inflammatory cytokines. This article addendum will provide a short summary of the original paper with our additional insights and interpretations.