Use Of Peripheral Stem Cells Research Articles

What Is the Most Appropriate Source for Hematopoietic Stem Cell Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

The introduction of peripheral stem cell (PSC) and cord blood (CB) as an alternative to bone marrow (BM) recently has caused important changes on hematopoietic stem cell transplantation (HSCT) practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

Autologous stem cell transplant (ASCT) for AIDS-related lymphoma (ARL)

High-dose therapy with ASCT is an established therapy for relapsed Non-Hodgkins (NHL) and Hodgkin's lymphoma (HL). Randomized trials have shown a benefit for this approach when compared to standard dose salvage therapy for HIV-negative NHL. Since these first trials, transplant-related mortality (TRM) has decreased due to the use of peripheral stem cells and improved supportive care. Concomitantly, the treatment of HIV infection has also improved. Highly active antiretroviral therapy (HAART) has improved hematologic and immune function in HIV positive patients. In addition, with the use of HAART and prophylactic antibiotics, the incidence of opportunistic infections has greatly decreased. This improvement in control of OIs and immunologic function in HIV infected patients due to HAART set the platform for the use of ASCT in patients with high-risk ARL. Herein we report the long-term follow-up of 32 patients with ARL who underwent ASCT at the City of Hope Cancer Center between 1998 and 2007. Median age at ASCT was 42 years. Histologies included Diffuse large cell n = 16, Burkitts n = 9, Anaplastic large cell n = 2, HL n = 5. The conditioning regimen consisted of CBV (carmustine 450 mg/m2, cyclophosphamide (CY) 100 mg/kg, VP16 60 mg/kg) in 28 patients and FTBI 1200 cGY/CY 100 mg/kg/VP16 60 mg/kg in 4 patients, All patients engrafted at a median of 10 days to an ANC >500 (range 5–19 days). One patient died of regimen-related cardiac toxicity. Other regimen-related toxicities included grade 3–4 hepatic toxicity n = 3, interstitial pneumonitis n = 2. OI's included PCP pneumonia in 2 patients who were not compliant with prophylaxis, CMV infection n = 3, VZV n = 2. One case of treatment related myelodysplasia was seen and the patient ultimately died of myelodysplasia while in remission from his ARL. Median HIV viral load at ASCT was 5726 copies/ml, with 25 patients having an undetectable viral load. Median CD4 count at ASCT was 156 (range 25–1064), which rose to 420 (range 95–1164) at 2-year follow-up. Only 10 patients had an undetectable VL at 2 years. Three patients who were in remission were lost to follow-up after 4 years. Median f/u for the entire group is 47 (range 0.7–104) months. Two-year overall survival is 80 percent (95% CI 66–89) and progression-free survival (PFS) is 81 percent (95% CI 67–90). In conclusion, this large single institution series of ASCT in ARL demonstrates that the procedure has low transplant-related mortality and can lead to long-term remission without deleterious effects on the underlying HIV infection.

28 years of high-dose therapy and SCT for neuroblastoma in Europe: lessons from more than 4000 procedures

Between 1978 and 2006, the European Group for Blood and Marrow Transplantation registered 4098 high-dose therapy (HDT) procedures followed by stem cell rescue (SCR) (3974 autologous/124 allogeneic) in patients with neuroblastoma. The 5-year rates for overall (OS) and event-free survival are 37 and 32%, respectively. The median age at diagnosis is 3.9 years (0.3-62 years) with 76 patients older than 18 years. Patients above 10 years carry a 2.5-fold higher risk. Younger patients cure significantly (<0.001) better with OS rates of 40 and 30% for age groups 2-4 years and 4-10 years, respectively. Their risks are about twofold higher than that of patients below 2 years with OS rates of 60%. The better the quality of remission status before HDT/SCT the better are the observed OS rates: 43% in CR1 (1199 patients) and 42% for CR2 (140 patients), and 36% for those in very good partial or partial remission (1413 patients) and 21% for those with sensitive relapse (134 patients). Patients reported with stable disease in first remission still had an OS rate of 30%. Multivariate analysis shows significantly better OS in the age group of less than 2 years (<0.0001), as well as a better quality of remission status before HDT/SCT (P<0.0001), with the use of peripheral stem cells (P=0.014), autologous SCT (P=0.031) and busulphan/melphalan HDT (P<0.001). Busulphan/melphalan HDT/SCT in first remission achieves an OS of 48%, while it is only 35% with other regimens (P<0.001), including melphalan alone, other melphalan-containing regimens, a variety of other drugs given as a single HDT as well as the addition of TBI or sequential HDT/SCT procedures. Further progress in the field may only be expected from large-scale international randomized trials.

Double-cycle high-dose chemotherapy with peripheral blood stem cells and hematopoietic growth factor support in patients with advanced solid tumor. A pilot study by the Hong Kong Biotherapy Group.

High-dose chemotherapy with autologous bone marrow transplantation has been useful in some patients with advanced breast, lymphoma, or germ cell tumors. Double-cycle high-dose chemotherapy may be able to deliver an even higher total dose within a given time period. It is important to determine whether peripheral blood stem cells and hematopoietic growth factors can diminish the hematopoietic toxicity of such a treatment. From November 1989 to May 1991, 14 patients were enrolled in two cycles of high-dose chemotherapy consisting of cyclophosphamide, 4.5 g/m2; cisplatin, 150 mg/m2; and etoposide, 900 mg/m2 in each cycle. The first five patients received peripheral blood stem cells harvested from 8-10 leukaphereses during steady state. The next nine patients, besides receiving peripheral blood stem cells mobilized by growth factors, also received either granulocyte-macrophage colony-stimulating factor (GM-CSF) at 250 micrograms/m2/day by two subcutaneous (s.c.) injections given 12 hours apart from day 6 until neutrophil recovery or granulocyte colony-stimulating factor (G-CSF) at 200 micrograms/m2 as daily s.c. injections. For the first five patients, there was a median of 14 days from the first day of absolute marrow suppression to neutrophil count exceeding 500/microliters and a median of 15 days for a platelet count exceeding 20,000/microliters. For the next nine patients, with the use of either G-CSF or GM-CSF, there was a median of 8 days for a neutrophil count exceeding 500/microliters and and a median of 11 days for a platelet count exceeding 20,000/microliters. With the use of peripheral stem cells and growth factors, high-dose chemotherapy could be given safely every 30 days with acceptable toxicity. A high complete response rate was seen in patients with nasopharyngeal carcinoma and in patients with small cell and non-small cell lung cancer who either had not received previous chemotherapy or who had responded to previous chemotherapy.

Detection and quantitation of malignant cells in the peripheral blood of multiple myeloma patients

One of the distinguishing features of multiple myeloma (MM) is the proliferation of plasma cells that home to the bone marrow (BM). However, there still remains some uncertainty concerning the presence of related malignant cells in the peripheral blood of myeloma patients. Using consensus oligonucleotide primers, we amplified the third complementary determining region (CDR3) of rearranged immunoglobulin heavy chain alleles from MM marrow samples by polymerase chain reaction (PCR). From the sequences of the products, we derived allele-specific oligonucleotides (ASO), and these were used in subsequent amplification reactions to detect malignant clones in the peripheral blood of myeloma patients. This method is highly specific and sensitive to 1 malignant cell in the background of 10(5) normal cells. Using this method we detected circulating malignant cells in 13 of 14 previously untreated MM patients. Furthermore, by applying ASO-PCR to artificial titrations of initial BM DNA sample into normal peripheral blood lymphocyte (PBL) DNA we were able to generate standard curves and quantitate the amount of tumor in the patient PBL. We observed a wide variation in the amount of circulating tumor between patients. In addition, we found that the incidence of circulating tumor cells was independent of BM tumor burden and stage of disease. The detection and quantitation of circulating tumor cells in the PBL of MM patients may offer an alternative assessment of the disease and may be an important consideration in the use of peripheral stem cells in bone marrow transplantation.

Detection and Quantitation of Malignant Cells in the Peripheral Blood of Multiple Myeloma Patients

One of the distinguishing features of multiple myeloma (MM) is the proliferation of plasma cells that home to the bone marrow (BM). However, there still remains some uncertainty concerning the presence of related malignant cells in the peripheral blood of myeloma patients. Using consensus oligonucleotide primers, we amplified the third complementary determining region (CDR3) of rearranged immunoglobulin heavy chain alleles from MM marrow samples by polymerase chain reaction (PCR). From the sequences of the products, we derived allele-specific oligonucleotides (ASO), and these were used in subsequent amplification reactions to detect malignant clones in the peripheral blood of myeloma patients. This method is highly specific and sensitive to 1 malignant cell in the background of 10(5) normal cells. Using this method we detected circulating malignant cells in 13 of 14 previously untreated MM patients. Furthermore, by applying ASO-PCR to artificial titrations of initial BM DNA sample into normal peripheral blood lymphocyte (PBL) DNA we were able to generate standard curves and quantitate the amount of tumor in the patient PBL. We observed a wide variation in the amount of circulating tumor between patients. In addition, we found that the incidence of circulating tumor cells was independent of BM tumor burden and stage of disease. The detection and quantitation of circulating tumor cells in the PBL of MM patients may offer an alternative assessment of the disease and may be an important consideration in the use of peripheral stem cells in bone marrow transplantation.

Use of peripheral stem cells in transplantation

Use of peripheral stem cells in transplantation