Peripheral Blood Stem Cell Transplantation As an Alternative to Bone Marrow Transplantation: an Overview
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Henry Ford Hospital Medical Journal Volume 39 Number 2 Article 10 6-1991 Peripheral Blood Stem Cell Transplantation as an Alternative to Bone Marrow Transplantation: An Overview Nalini Janakiraman Follow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournal Part of the Life Sciences Commons, Medical Specialties Commons, and the Public Health Commons Recommended Citation Janakiraman, Nalini (1991) "Peripheral Blood Stem Cell Transplantation as an Alternative to Bone Marrow Transplantation: An Overview," Henry Ford Hospital Medical Journal : Vol. 39 : No. 2 , 103-107. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol39/iss2/10 This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Peripheral Blood Stem Cell Transplantation as an Alternative to Bone Marrow Transplantation: An Overview Nalini Janakiraman, MD' Slem cells capable of resloring hemalopoiesis following lethal bone marrow injury circulate in Ihc blood of many animals, including humans. When collected ihrough leukapheresis and reinfused following high-dose chenwiherapy, slem cells offer a Irealmenl optiim not currently open lo some patients who are unable lo undergo autologous hone marrow transplantation because of tumor involvement in the pelvis, prior pelvic radiation, or intolerance to general anesthesia. After stem cell infusion, hematologic and immunologic recovery are rapid in comparison lo that after autologous hone marrow reinfusion: however, in some cases platelet engraftment is slower. There is some evidence lhal tumor conlaminalion in the peripheral hlood is much less than in the marrow. In any event, most relapses if malignant disease occur at the site of origin and represent Ireatmeni failure ralher lhan growlh if reinfused malignant cells. Prospective controlled trials are needed to evaluate stem celt in comparistm to autologous hone marrow iransplanlalion. (Henry Ford Hosp Med J 1991:39:103-7) ematopoietic stem cells capable of restoring hemalopoi mia, cells obtained by leukapheresis during the chronic phase H esis when infused following lethal bone marrow injury are have been used for successful engraftment during blast crisis known to circulate in the blood of many animals, including non- treated by myeloablative chemotherapy (7). A prospective study human primates (1,2). Many bone marrow transplant centers of the treatment of aplastic anemia by allogeneic bone marrow now use stem cells obtained from peripheral blood by leukaphe transplantation with and without donor buffy coat cells showed resis as an altemative to bone marrow transplantation in some that the addition of buffy coat cells reduced the rejection rate (8). situations (3-5). A high rate of sustained graft and of acute and chronic graft ver sus host disease confirmed engraftment of peripheral blood stem cells. Blood-derived granulopoietic proliferation can be Hematopoiesis and Peripheral Blood Stem Cells sustained in long-term cultures (up to eight weeks) with genera The hierarchy of the hematopoietic system is depicted in the tion of CFU-GM cells similar to that of bone marrow cells, de Figure. The pluripotent stem cells are capable not only of differ spite some qualitative differences (9). Finally, an increasing entiation along different lines but also of self-renewal. These numberof patients are now being treated with high-dose chemo cells are essential for successful engraftment following high- therapy and autologous peripheral blood stem cell reinfusion. dose chemotherapy. There is currently no assay to measure these cells, and we do not understand fully their phenotypic characteristics. Cultures now performed in the laboratory, e.g., Long-term Engraftment with colony-forming unit-granulocyte erythroid macrophage mega Peripheral Blood Stem Cells karyocyte (CFU-GEMM), colony-forming unit-granulocyte In the absence of some form of cell tagging, it is difficult to macrophage (CFU-GM). and burst-forming unit-erythrocyte, prove that the hematopoietic recovery is from infused bone mar measure more committed cells. CD-34 antigen, an antigen ex row or peripheral blood stem cells and is not spontaneous. Be pressed on the surface of stem cells, is used as a marker, but it cause the myeloablative regimen is the same as that used prior may be a marker for a cell which is derived by several multipli to allogeneic transplantation, recovery almost certainly results cations beyond the stem cell, closer to the more committed cells. from the engraftment of infused cells. Several reports of follow- Studies in mice, dogs, and baboons have shown that hema topoietic cells capable of engraftment circulate in peripheral blood. Multiple canine studies (6) have demonstrated the feasi bility of obtaining such cells by apheresis and utilizing them to .Submilled for puhlicalion: Augusi 16. 1990. reconstitute hematopoiesis after lethal radiation. Ample evi Accepled for publication: ,Seplember 13, 1990, dence shows that stem cells can also be obtained from the pe *Division of Hematology/Oncology, Henry Ford Hospilal. Address correspondence lo Dr. Janakiraman, Division of Hemalology/Oncology, Henry ripheral blood of human beings. In chronic granulocytic leuke Ford Hospital, 2799 W Grand Blvd, Detroit, Ml 48202, Henry Ford Hosp Med J—Vol 39, No 2, 1991 PBSC Transplantation—Janakiraman 103 reinfusion of malignant cells. If more effective therapy could eliminate residual disease, autologous bone marrow could be pluripotent stem compared to the use of peripheral blood stem cells more accu rately. More rapid hematologic recovery may follow peripheral blood transplantation compared to bone marrow transplantation •nixed myeloid progenitor lymphoid progenitor (II). Becau.se hematologic recovery is earlier by several days, _|| the risk of infection, the mortality, and the length of hospital stay are reduced. Earlier recovery is attributed to the reinfusion of burst-rorming unll (eryttirold) more committed cells than are provided by the bone marrow. Immunologic reconstitution is also more rapid with peripheral blood stem cell transplantation compared to autologous bone marrow transplantation (11,12). erytfirold megakaryocyte granulocyte/monocyte eosinophil progenitor progenitor progenitor progenitor Peripheral Blood Stem Cell Collection ©C^ Stem cells are collected by repeated leukapheresis either at red cells platelets monocytes neutrophils basophils eosinophils lymphocytes random for several consecutive days (steady state collection) or during recovery from chemotherapy-induced myelosuppression (recovery phase collection). A single leukapheresis in a healthy Figure—Hematopoietic stem and progenitor cells. individual will yield 0.3 x 10'* CFU-GM/kg. About 20 to 30 steady state collections are needed to obtain the number of CFU- GM obtained from bone marrow harvest. This time-consuming procedure may be the only option for some patients who have up for as long as two years confirm long-term engraftment with been extensively pretreated. Kessinger et al (13) required a me peripheral blood stem cell transplantation. dian of 8 (range 6 to 17) steady state leukaphercses to collect 0.6 Several studies of peripheral blood stem cell transfusion have X 104 (0 to 98.6) CFU-GM/kg. The granulocyte and platelet en suggested a delay of platelet engraftment when compared to graftment durations were similar to autologous bone marrow bone marrow tran.splantation. There may be fewer megakaryo transplant (25 days). cyte progenitors in the peripheral blood, and megakaryocyte Richman et al (14) reported in 1976 that during recovery from progenitors are particularly susceptible to the process of leu chemotherapy-induced neutropenia the circulating granulocytic kapheresis, freezing, and thawing. Cultured CFU-GEMM ob stem cells (colony-forming unit-culture) increased from 6 to 23 tained from peripheral blood stem cells and stained with mono per 2 X 10-'' mononuclear cells plated. Cyclical changes in the clonal antibodies to platelet glycoprotein 111 confirmed fewer concentration of stem cells with a maximum value of 20 times megakaryocyte precursors in the peripheral blood compared to the baseline were demonstrated. They estimated that enough bone marrow (14% versus 87%) (10). This reduction may result stem cells for transplant could be obtained from the peripheral from culture conditions and be overcome by high cell numbers. blood by appropriately timed 17 liter leukapheresis. This information stimulated the increasing use of peripheral blood stem cell transplantation. The number of stem cells col Advantages of Peripheral Blood Stem Cells lected following induction and consolidation therapy for acute In patients who have had radiation therapy to the pelvis or myelogenous leukemia (AML) in very eariy remission was ade who have tumor involvement of the pelvic bone, the bone mar quate for transplantation after myeloablative chemotherapy row harvest site, collection of peripheral blood stem cells by (15). Moderately intensive chemotherapy was used to facilitate leukapheresis offers a means to obtain stem cells. This is also stem cell collection in other disease states, i.e., cyclophospha true for patients with contraindications to general anesthesia. mide 1.5 or 4 g/M-, doxorubicin 90 mg/M-, and vincristine 1.4 Any other advantages to peripheral blood stem cells are not well mg/M-