Biology of Blood and Marrow Transplantation
Volume 12, Issue 1 , Pages 111-112, January 2006

Increased Mean Corpuscular Volume after Autologous Hematopoietic Stem Cell Transplantation: Incidence and Significance

Department of Hematology-Oncology, Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma

Article Outline

 

Myelodysplasia and acute leukemia have been reported after high-dose chemotherapy and autologous stem cell transplantation [1, 2]. Mean corpuscular volume (MCV) elevation after the administration of chemotherapy and its relationship to the risk of secondary leukemia are suggested in long-term survivors [3, 4]. The incidence and significance of MCV elevation after high-dose chemotherapy and autologous hematopoietic stem cell transplantation are unknown.

We performed a retrospective analysis of 130 consecutive patients who underwent autologous hematopoietic stem cell transplantation between January 1999 and December 2003. Patients with relapse of disease within 6 months of transplantation and those with inadequate follow-up were excluded. Sixty-three (48%) of 130 patients (non-Hodgkin lymphoma, n = 20; neuroblastoma, n = 16; Hodgkin disease, n = 8; breast cancer, n = 8; myeloma, n = 7; acute myelogenous leukemia, n = 2; and testicular cancer, n = 2) were eligible for analysis. The complete blood count profile obtained by using an automated Coulter counter (Beckman Coulter, Inc, Fullerton, CA) (and manual evaluation, when available) was analyzed at transplantation, at 6 months, at 1 year, and yearly after transplantation. Patient characteristics were analyzed, including time to achieve engraftment (absolute neutrophil count >500/μL and platelet count >20000/μL) and time to achieve long-term hematological recovery (hemoglobin >12 g/dL, white cell count >4000/μL, and platelet count >150000/μL). When available, a history of alcohol abuse, abnormal liver or thyroid function, and vitamin B12 or folate deficiency were recorded.

The median age was 41 years (range, 1-76 years). Thirty-seven were men, and 26 were women. All patients underwent peripheral blood stem cell transplantation; 6 patients underwent double autotransplantation. The median time to engraftment for neutrophils and platelets was 12 and 14 days, respectively. The median time to long-term hematologic recovery as defined previously was 289 days; 27 (81%) patients had suboptimal hematopoietic recovery at 6 months. At a median follow-up of 30 months (range, 6-73 months), 33 (52.8%) of 63 patients displayed increased MCV 6 months after transplantation (Table 1). The MCV increase was observed above reference values at all pediatric ages. For children aged 6 months to 5 years (reference range, 75-87 fL), the mean pretransplantation MCV of 90.8 fL increased to 94 fL. In children aged 6 to 18 years (reference range, 77-95 fL), the mean pretransplantation MCV of 90.8 fL increased to 96 fL. Persistent MCV elevation was observed in 65% and 50% of patients at 1 and 2 years after transplantation, respectively. Further investigations of macrocytosis in form of liver function tests, thyroid function tests, vitamin B12 or folate deficiency, and history of alcohol abuse had negative results. MCV elevation was independent of age, disease, CD34 cell dose, conditioning regimen, and number of transplantations.

Table 1. Mean Corpuscular Volume in Autologous Hematopoietic Stem Cell Transplant Recipients
MCVBaseline (fL)6 mo (fL)1 y (fL)Incidence
Adults (n=43)97.5102.7(range,99.5-11.2)101.3(range,92.5-105)15/43(35%)
Children (n = 20)90.894.1(range,90.3-104)97.3(range,78.7-100)18/20(91%)

MCV reference range: adults, 81-99 fL; children, 75-87 fL.

Increased MCV after high-dose therapy and transplantation likely reflects injury to the bone marrow microenvironment, ineffective erythropoiesis, or both. A previous study with autotransplantation in breast cancer reported persistently increased MCV in 25% of transplant recipients [5]. These results were independent of age, high-dose regimen, number of reinfused stem cells, and stem cell source. Patients with double (n = 12) versus single (n = 119) transplantations showed significantly higher MCV. No secondary graft failure, myelodysplasia, or leukemia was encountered [5]. Our results reflect a higher incidence of macrocytosis. Additionally, we provide results in pediatric transplant recipients.

Persistent elevation of MCV without development of anemia or overt myelodysplasia is common after autologous transplantation, with an incidence of approximately 50%. Long-term follow-up is needed to determine its significance (if any).

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References 

  1. Sobecks RM , Le Beau MM , Anastasi J , Williams SF . Myelodysplasia and acute leukemia following high-dose chemotherapy and autologous bone marrow or peripheral blood stem cell transplantation . Bone Marrow Transplant . 1999;23:1161–1165
  2. Darrington DL , Vose JM , Anderson JR , et al.   Incidence and characterization of secondary myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemoradiotherapy and autologous stem-cell transplantation for lymphoid malignancies . J Clin Oncol . 1994;12:2527–2534
  3. Karvellas CJ , Sawyer M , Hamilton M , Mackey J . Effect of capecitabine on mean corpuscular volume in patients with metastatic breast cancer . Am J Clin Oncol . 2004;27:364–368
  4. Dohy H , Genot JY , Imbert M , D’Agay MF , Sultan C . Myelodysplasia and leukaemia related to chemotherapy and/or radiotherapy. A haematological study of 13 cases. Value of macrocytosis as an early sign of bone marrow injury . Clin Lab Haematol . 1980;2:111–119
  5. Nieboer P , de Vries EG , Mulder NH , et al.   Long-term haematological recovery following high-dose chemotherapy with autologous bone marrow transplantation or peripheral stem cell transplantation in patients with solid tumors . Bone Marrow Transplant . 2001;27:959–966

PII: S1083-8791(05)00675-0

doi:10.1016/j.bbmt.2005.09.011

Biology of Blood and Marrow Transplantation
Volume 12, Issue 1 , Pages 111-112, January 2006

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