JAC Advance Access originally published online on February 13, 2006
Journal of Antimicrobial Chemotherapy 2006 57(4):795-796; doi:10.1093/jac/dkl038
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Correspondence |
Delayed myeloid engraftment due to vancomycin in allogeneic haematopoietic stem cell transplant recipients
1 Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA; 2 Division of Hematology/Oncology and Bone Marrow Transplant, Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
* Corresponding author. Tel: +1-713-441-1961; Fax: +1-713-793-1232; E-mail: kamble{at}sbcglobal.net
Keywords: cytopenia , antibiotics , neutropenia
Sir,
In haematopoietic transplantation, myeloid and megakaryocytic engraftment typically occurs in tandem at a median of 15 days (range = 5–41 days).1 Various factors, including the age of the recipient, stem cell dose (CD34+ cells), source of stem cells (bone marrow versus mobilized blood stem cells), degree of HLA matching, administration of colony stimulating factors, T cell depletion and infections, are known to affect the process of engraftment.1,2 Vancomycin is commonly used during the course of haematopoietic transplantation. Although vancomycin-induced neutropenia has been reported,3,4 in the presence of other confounding factors such as infection, sepsis and other antibiotics, a direct causal relationship may be difficult to establish. We herein report a case of rapid megakaryocytic engraftment with normalization of platelet counts in the absence of myeloid engraftment and restoration of myeloid haematopoiesis following discontinuation of vancomycin.
A 59-year-old male received a non-myeloablative allogeneic haematopoietic stem cell transplant (allo-SCT) for intermediate risk (normal cytogenetics) acute myelogenous leukaemia (AML-M4) in first complete remission (CR1) from a 6/6 HLA-matched unrelated donor. A total of 6.1 x 106 CD34+ cells were infused following sub-ablative conditioning (busulfan 0.8 mg/kg every 6 h x 2 days, fludarabine 30 mg/m2 x 3 days and alemtuzumab 10 mg x 5 days). Graft versus host disease (GVHD) prophylaxis was performed with a short course of methotrexate (10 mg/m2 on day +1; 5 mg/m2 on day +3; and 5 mg/m2 on day +6) and tacrolimus. The transplant course was uncomplicated except for a catheter-insertion-site infection on day +12, for which intravenous vancomycin (1 g every 12 h) was initiated. The peak and trough vancomycin levels were 27.1 mg/L (range = 30.0–40.0 mg/L) and 8.4 mg/L (range = 5.0–10.0 mg/L), respectively. The patient remained afebrile, blood cultures were negative and he did not receive any other antibiotic. Figure 1 demonstrates the neutrophil and platelet nadir along with the haematopoietic reconstitution. Megakaryocytic engraftment (platelets >20 000/dL x 3 consecutive days in the absence of transfusion) occurred on day +10 without myeloid engraftment. On day +18 colony stimulating factor (G-CSF; 480 µg subcutaneously daily) was initiated. On day +19 the platelet count was 160 000/dL without any evidence of myeloid engraftment (neutrophils = 2, WBC = 100/dL). On day +21, vancomycin was discontinued; myeloid engraftment occurred on day +23 (13 days after megakaryocytic engraftment). An absolute lymphocyte count (ALC) at myeloid engraftment was 18 cells/mm3. Lymphocyte recovery (ALC 
500 cells/mm3) occurred in 70 days. Engraftment studies on day 30 confirmed 99.5% donor chimerism. Pre-emptive ganciclovir was initiated for cytomegalovirus (CMV) antigenaemia on day 21; the patient had no CMV disease. Currently, at 6 months post-transplantation, he has no evidence of GVHD.
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Megakaryocytic engraftment on day +10 and complete platelet recovery (platelets >150 000/dL) by day +19 in the absence of myeloid engraftment provides evidence supporting the occurrence of granulocytopenia associated with vancomycin therapy. A previous report5 had described vancomycin-associated granulocytopenia after successful engraftment following an auto-transplant. A bone marrow specimen obtained at the time of neutropenia demonstrated in vitro suppression of progenitor cell growth at increasing concentrations of vancomycin.3 The patient represents the first published case of vancomycin-associated failed myeloid engraftment.
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References
1.
Bensinger WI, Martin PJ, Storer B et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 2001; 344: 175–81.
2.
Davies SM, Kollman C, Anasetti C et al. Engraftment and survival after unrelated-donor bone marrow transplantation: a report from the national marrow donor program. Blood 2000; 96: 4096–102.
3. Kesarwala HH, Rahill WJ, Amaram N. Vancomycin induced neutropenia. Lancet 1981; i: 1423.
4.
Segarra-Newnham M, Tagoff SS. Probable vancomycin-induced neutropenia. Ann Pharmacother 2004; 38: 1855–9.
5. Meehan KR, Verma UN, Esteva-Lorenzo F et al. Suppression of progenitor cell growth by vancomycin following autologous stem cell transplantation. Bone Marrow Transplant 1997; 19: 1029–32.[Medline]
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