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ctt-journal > Stankevich et al. (Abstract)

Stankevich et al. (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 2, No. 5, 2009
doi: 10.3205/ctt-2009-No5-abstract81
© The Authors. This abstract is provided under the following license:
Creative Commons Attribution 3.0 Unported


Abstract accepted for "Joint EBMT Pediatric Working Party – 3rd Raisa Gorbacheva Memorial Meeting on Hematopoietic Stem Cell Transplantation", Saint Petersburg, Russia, September 17–20, 2009

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The comparative characteristic toxicity and immunosuppressive activity both tacrolimus and cyclosporine in patients undergoing allo-HSCT

Yulia A. Stankevich, Ludmila S. Zubarovskaya, Elena V. Semenova, Sergey M. Alexeev, Elena V. Babenko, Boris V. Afanasyev

Memorial R.M. Gorbacheva Institute of Children Hematology and Transplantation, St. Petersburg Pavlov State Medical University, St. Petersburg, Russia

Correspondence: Memorial R.M. Gorbacheva Institute of Children Hematology and Transplantation, St. Petersburg Pavlov State Medical University, 6/8, Tolstoy str., St. Petersburg, 199044, Russia, E-mail: juliastan@spam is badmail.ru

Abstract

Background: Graft-versus-host disease (GVHD) still remains one the major obstacles to successful allogeneic hematopoietic cell transplantation (HSCT). GVHD is a major cause of morbidity and mortality even when the recipient and donor are matched at the major histocompatibility complex. In its acute and chronic forms, GVHD has an important impact on survival and the recipient’s quality of life. The ability to prevent GVHD—i.e., the application of successful prophylaxis—is the cornerstone of success. Immunosupression with pharmacological agents such as cyclosporine (CsA) or tacrolimus (Tx) is more often used for GVHD prophylaxis. Because they share a common intracellular target, the toxicity profiles of CsA and Tx are very similar. We found Tx to be superior for the prophylaxis of acute GVHD, but more toxic. While hypertension and myelosupression is more commonly seen with CsA, neurological, nephrology, and gastrointestinal side effects are more often associated with the administration of Tx.

Patients and methods: From 2000 to December 2008, 171 patients (pts) received allogeneic HSCT. In two patients allo-HSCT was repeated because of relapse of disease, so the total number of transplantations was 173. Patients and donor characteristics, type of allo-HSCT, and preparing regimens are shown in Table 1.

Table 1. Patient’s and transplant’s characteristics

    Number of patients
Number of allo-HSCT   173
  Related HSCT 64
  Unrelated HSCT 109
  Haploidentical HSCT 17
Patients age median, y (range) 31.6 (14–66)  
Diagnosis    
AML/MDS   57/7
  remission  
  relapse  
ALL   58
  remission  
  relapse  
Lymphoma (NHL+HD)   16
CML   25
  chronic phase  
  acceleration phase  
Aplastic anemia   6
Other   4
Source of HSC    
  BM 57
  PBSC 99
  BM + PBSC 17
HLA    
  full match 118
  1 mismatch 28
  2 mismatch 10
  haplo 17
Prophylaxis of GVHD    
  CsA + MMF 14
  CsA + Mtx 83
  CsA + Mtx + MMF 6
  Tx + MMF 46
  CsA 8
  Other 12
Myeloablative regimen   47
Nonmyeloablative regimen   125
ABO-compatibility   71
ABO-incompatibility   102
Sex-compatibility   92
Sex-incompatibility   81
Transplanted donor cells    
  NC x 10 8/kg 6.7 n=19 (2.6–14.4)
  CD34 x 10 6/kg 5.13 n=21 (0.3–18.3)

 

Results: There was no significant difference in survival. The 6-month overall survival rate was 53% for the Tx group and 65% for the CsA group; the 6-month relapse-free survival rate was 42% (Tx) vs. 50% (CsA). There was no difference in rates of relapse between the two groups.

Infections were the most common cause of death, accounting for 33% of deaths. Other causes of death included acute GVHD (31%), relapse (20%), and multisystem organ failure (8%). The incidence of infections was similar in the two study groups.

Although a significantly greater proportion of patients was treated with cyclosporine, the incidence of grades II-IV acute GVHD was significantly lower in patients who received tacrolimus (29% vs. 54% in related HSCT and 32% vs. 60% in unrelated HSCT).

Despite the fact that Tx proved to be superior as a prophylaxis of acute GVHD, it was found to be more toxic. The incidence of hypertension was significantly higher in the CsA group (38% vs. 24%), but neurological complications (headache, tremor, paresthesia) were significantly higher in the Tx group (44% vs. 30%). Gastrointestinal disturbances were more common in the Tx group (46% vs. 36%, NS), as was hyperglycemia (24% vs. 16%), nephrotoxicity (19% vs. 15%), and metabolic disturbances (11% vs. 7%).

Conclusion: The use of Tx seems to be preferable in groups with a higher risk of developing GVHD because it has a more potent immunosuppressive effect. But Tx has more toxic complications such as neurological, nephrology, gastrointestinal, and metabolic disturbances. On the other hand, hypertension and myelosuppression is more commonly seen with CsA.

Keywords: graft-versus-host disease, allogeneic hematopoietic cell transplantation, immunosuppressive therapy

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