Spontaneous transient rise of CD34 cells in peripheral blood after 72 hours in patients suffering from advanced malignancy with anemia: Effect and prognostic implications of treatment with placental umbilical cord whole blood transfusion

Cord blood, because of its rich mix of fetal and adult hemoglobin, platelet and WBC counts, and a plasma filled with cytokine and growth factors, as well as its hypoantigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood during emergencies or any etiology of blood loss.

Study design: In the present study transfusion-related CD34 levels of the peripheral blood from six randomly selected patients suffering from advanced clinical Stage IV malignancy were analyzed between 16 August 1999 and 16 May 2001. This study attempts to ascertain the fate of hematopoietic stem cells (CD34) after placental umbilical cord whole blood transfusion, as assessed from the peripheral blood CD34 level 72 hours after cord blood transfusion in sex- and HLA-randomized patients.

Results and analysis: Among the six cases, Case 2 (breast sarcoma) received the lowest amount of card blood (6 units), while Case 6 (breast cancer) received the largest amount (32 units). The youngest patient, suffering from non-Hodgkin's lymphoma (Case 3), was a 16-year-old boy who received eight units of cord blood to combat anemia. Other patients received amounts varying from 7-15 units: Case 4 received 15 units (metachronous lymph node metastatsis), Case 1 received 14 units (breast cancer), and Case 5 received seven units (lung cancer). There was no transfusion-related clinical immunological or nonimmunological reaction. Studies of CD34 levels showed an initial rise followed by a fall in two cases, two cases registered very little effect on the CD34 level, i.e., no change from the baseline, and one case demonstrated a very slow rise from the baseline. However, one case showed a frequent steep rise up to 99% and a sustained high CD34 level. This patient is alive with clinical remission of the disease.

Conclusion: It appears from this preliminary study that freshly collected cord blood transfusion may cause a transient transplant impact of transfused cord blood CD34 stem cells on the host without provoking clinical graft vs host disease due to a of background immune suppression in advanced malignancy. The growth factor cytokine system of freshly collected cord blood may have a potentiating role on the immune system of the host.

Safe; Placental cord whole blood transfusion; Anemia in advanced cancer; Cord blood; Transient transplant effect; CD34 hematopoietic stem cells

[1] Smith R.E. Jr, Tchekmedyian S.: "Practitioners'practical model for managing cancer elated anemia". Oncology (Huntington), 2002, 9 (suppl. 10), 55.

[2] Pirker R., W iesenberger K., Pohl G., Minar W.: "Anemia in lung cancer: clinical impact and management". Clin. Lung. Cancer, 2003, 5, 80.

[3] T chekmedyian N.S.: "Anemia in cancer patients: significance, epi demiology, and current therapy". Oncology (Huntington), 2002, 9 (suppl. 10), 17.

[4] Steensma D.P.: "Management of anemia in patients with cancer" Curr. Oncol. Rep., 2004, 6, 297.

[5] Kolesar J.M.: "Novel approaches to anemia associated with cancer and chemotherapy". Am. J. Health Syst. Pharrn., 2002, 59 (suppl 4), S8.

[6] Harrison L.B., Shasha D., Homel P.: "Prevalence of anemia in cancer patients undergoing radiotherapy: prognostic significance and treatment". Oncology, 2002, 63 (suppl. 2), 11.

[7] Ludwig H., Fritz E.: "Anemia of cancer patients: patient selection and patient stratification for epoetin treatment". Semin Oncol., 1998, 25 (suppl. 7), 35.

[8] "Guideline for the gamma irradiation of the blood components for the prevention of the transfusion associated graft vs host disease. BCSH blood transfusion task force". Transfusion Med., 1996, 6, 261.

[9] Goodnough L.T.: "Transfusion Medicine - Blood Conservation Second of Two Parts". 1999, 340, 525.

[10] T scherning-Caspcr C., Papadogiannakis N., Anvret M., Stolpe L., Lindgren S., Bohlin A.B. et al.: " T he trophoblastic epithelial barrier is not infected in full-term placentae of human immunodeficiency virus-seropositive mothers undergoing antiretroviral therapy". J. Viral., 1999, 73, 9673.

[11] Bhattacharya N.: "Placental urnb山cal cord whole blood transfusion: a safe and genuine blood substitute for patients of the underresourced world at emergency". J. Am. Coll. Surg., 2005, 200, 557.

[12] Bhattacharya N.,M ukherjee K.L.,C hettri M.K.,B anerjee T.,M ani U., Bhattacharya S.: "A study report of 174 units of placental umbilical cord whole blood transfusion in 62 patients as a rich source of fetal hemoglobin supply in different indications of blood transfusion". Clin. Exp. Obstet. Gynecol., 2001, 28, 47.

[13] Schmitz-Winnenthal F.H., Volk C., Z'graggen K., Galindo L., Nummer D., Ziouta Y. et al.: "High frequencies of functional tumor-reactive T cells in bone marrow and blood of pancreatic cancer patients". Cancer Res., 2005, 65, 10079.

[14] Lee T.H., Paglieroni T., Ohto H., Holland P.V., Busch M.P.: "Survival of donor leukocyte subpopulations in immunocompetent transfusion recipients: frequent long-term microchimerism in severe trauma patients". Blood, 1999, 93, 3127.

[15] Utter G.H., Owings J.T., Lee T.H., Paglieroni T., Reed W.F., Gosselin R.C. et al.: "Blood transfusion is associated with donor leukocyte microchimerism in trauma patients". J. Trauma, 2004, 57, 702.

[16] Lee T.H., Paglieroni T., Utter G.H., Chafets D., Gosselin R.C., Reed W. et al.: "High-level long-term white blood cell microchimerism after transfusion of leukoreduced blood components to patients resuscitated after severe traumatic injury". Transfusion, 2005, 45, 1280.

[17] Lee T.H., Paglieroni T., Ohto H., Holland P.V., Busch M.P.: "Survival of donor leukocyte subpopulations in immunocompetent transfusion recipients: frequent long-term microchimerism in severe trauma patients". Blood, 1999, 93, 3127.

[18] Szekeres-Bartho J.: "Immunological relationship between the mother and the fetus". Int. Rev. fmmunol., 2002, 21, 471.

[19] Carosella E.D.: "HLA-G: fetomaternal tolerance". C.R. Acad. Set Ⅲ, 2000, 323, 675.

[20] Ishitani A., Sageshima N., Lee N., Dorofeeva N., Hatake K., Marquardt H., Geraghty D.E.: "Protein expression and peptide binding suggest unique and interacting functional roles for HLA-E, F, and G in maternal-placental immune recognition". J. Immunol., 2003, 171, 1376.

[21] Sargent LL.: "Maternal and fetal immune responses dunng pregnancy". Exp. Clin. lmmunogenet., 1993, 10, 85.

[22] Le Bouteiller P., Rodriguez A.M., Mallet V., Girr M., Guillaudeux T., Lenfant F.: "Placental expression of HLA class I genes". Am J. Reprod. lmmunol., 1996, 35, 216.

[23] McCracken S., Layton J.E., Shorter S.C., Starkey P.M., Barlow D.H., Mardon H.J.: "Expression of granulocyte-colony stimulating factor and its receptor is regulated during the development of the human placenta". J. Endocrinol., 1996, 149, 249.

[24] Lee T.-H., Donegan E.A., Slichter S., Busch M.P.: " Transient increase in circulating donor leukocytes following allogeneic transfusions in immunocompetent recipients compatible with donor cell proliferation". Blood, 1995, 85, 1207.

[25] Roitt I., Brostoff J., Male D.: " Immunology", 6'h edition. Mosby 2001, 12, 205.

[26] Joshi S.S., Vu U.E., Lovgren T.R., Lorkovic M., Patel W., Todd G.L. et al.: "Comparison of phenotypic and functional dendritic cells derived from human umbilical cord blood and peripheral blood mononuclear cells". J. Hematother. Stem. Cell Res., 2002, 11, 337.