Mobilization and collection of peripheral blood CD34+ cells from patients with Fanconi anemia

Blood ◽  
2001 ◽  
Vol 98 (10) ◽  
pp. 2917-2921 ◽  
Author(s):  
James M. Croop ◽  
Ryan Cooper ◽  
Christine Fernandez ◽  
Vicki Graves ◽  
Susan Kreissman ◽  
...  

Abstract A potential therapeutic option for patients with Fanconi anemia is collection of peripheral blood stem cells prior to the development of severe pancytopenia. These hematopoietic cells potentially could be infused when symptomatic bone marrow failure develops, as autologous rescue after chemotherapy in the event of leukemic transformation, or as targets for gene therapy. Eight patients with Fanconi anemia were mobilized with 10 μg/kg per day of granulocyte colony-stimulating factor (median, 10 ± 4 days) to determine the feasibility of collecting peripheral blood stem cells for future use. Six patients achieved a peripheral blood CD34+ count of ≥ 6/μL and underwent apheresis. The collection goal was 2 × 106 CD34+ cells/kg based on a predicted weight 5 years from the date of collection. A mean of 2.6 ± 0.9 × 106 CD34+ cells/kg of the weight at the time of collection were collected, which corresponded to 1.9 ± 0.4 × 106 CD34+cells/kg of the target weight. The collections required a mean of 4 ± 3 days (range, 2-8 days) of apheresis. Six of the 8 subjects had ≥ 1 × 106 CD34+ cells/kg cryopreserved based on both actual and target weights, and 4 subjects had ≥ 2 × 106 CD34+ cells/kg cryopreserved based on the target weight. These results suggest that some patients with Fanconi anemia can have adequate numbers of CD34+ cells mobilized and collected from the peripheral blood prior to the onset of severe bone marrow failure, but they may require an extended mobilization and multiple days of collection.

Blood ◽  
2003 ◽  
Vol 101 (2) ◽  
pp. 446-453 ◽  
Author(s):  
Ahmet H. Elmaagacli ◽  
Rudolf Peceny ◽  
Nina Steckel ◽  
Rudolf Trenschel ◽  
Hellmut Ottinger ◽  
...  

Outcomes of highly purified CD34+ peripheral blood stem cell transplantation (PBSCT) for chronic phase chronic myeloid leukemia (CML) (n = 32) were compared with those of PBSCT (n = 19) and of bone marrow transplantation (BMT) (n = 22) in the HLA-compatible sibling donor setting. Median follow-up was 18 months after CD34+-PBSCT and unmanipulated PBSCT and 20 months after BMT. CD34+-PBSCT was associated with delayed T-cell immune reconstitution at 3 months and 12 months after transplantation compared with PBSCT (P < .001) or BMT (not significant [NS]). The estimated probability of grades II to IV acute graft-versus-host disease (GVHD) was 60% ± 13% for the PBSCT group, 37% ± 13% for the BMT group, and only 14% ± 8% for the CD34+-PBSCT group (CD34-PBSCT versus BMT,P < .01; and CD34-PBSCT versus PBSCT,P < .001). The probabilities for molecular relapse were 88% for CD34+-PBSCT, 55% after BMT, and 37% after PBSCT (CD34+-PBSCT versus PBSCT,P < .03). Cytogenetic relapse probability was 58% after CD34+-PBSCT, 42% after BMT, and 28% after PBSCT (NS). After CD34+-PBSCT, 26 of 32 patients received a T-cell add-back. Hematologic relapse occurred in 4 of 22 patients after BMT, in 3 of 19 patients after PBSCT, and in only 1 of 32 patients after CD34+-PBSCT. The occurrence of a hematologic relapse in patients receiving CD34+-PBSC transplants was prevented by donor leukocyte infusions, which were applied at a median of 4 times (range, 1-7 times) with a median T-cell dose of 3.3 × 106 × kg/body weight [at a median] beginning at day 120 (range, 60-690 days). The estimated probability of 3-year survival after transplantation was 90% in the CD34+-PBSCT group, 68% in the PBSCT group, and 63% in the BMT group (CD34-PBSCT versus BMT, P < .01; and CD34-PBSCT versus PBSCT, P < .03). Transplantation of CD34+-PBSCs with T-cell add-back for patients with CML in first chronic phase seems to be safe and is an encouraging alternative transplant procedure to BMT or PBSCT.


2021 ◽  
Author(s):  
Pinki Devi ◽  
Ganapathi Bhat ◽  
Harish S. Ahuja

Abstract Introduction The use of hematopoietic stem cells for autologous and allogeneic transplantation has increased in the recent past significantly, due to introduction of newer chemotherapeutic drugs, immunological techniques, and better stem cell technology. Among the bone marrow and peripheral blood stem cells, collection of the latter being more convenient to the patient and associated with faster granulocyte and platelet engraftment has been known as preferred method for mobilization. Peripheral blood stem cells can be extracted from the autologous or allogeneic donor. Mobilization of the stem cells for autologous stem cell transplant is traditionally done using growth factors alone or in combination with chemotherapy, with or without an additional mobilizing agent. A significant number of hematological malignancy patients are poor mobilizers, (i.e., they are unable to achieve the minimal target cell dose during their first round of mobilization).Therefore, a prediction for a successful stem cell mobilization ideally should be made before initiating any apheresis procedure to spare those with a low rate of success from the risks associated with apheresis procedure. Preapheresis CD34 cell count can predict postapheresis yield and hence, can help to reduce the collection sessions. Reduction of apheresis sessions decreases the discomfort, inconvenience, time, and monetary expenses. Objectives This study was aimed to analyze preapheresis and postapheresis CD34+ cell counts. Materials and Methods Patients of any age and gender with diagnosis of hematological malignancies admitted for autologous stem cell transplantation for hematological malignancies (including Hodgkin lymphoma, non-Hodgkin lymphoma, and multiple myeloma) and germ cell tumors in our institute from July 2008 to July 2016 were included in the study. The post-GCSF CBC, preapheresis CBC, CD34+ cell counts, and postapheresis CBC, CD34+ cell counts, mononuclear cell counts to predict the outcome of amount of yield. The effect on engraftment will be measured according to the defining criteria of achieving a sustained peripheral blood neutrophil count of >500 × 106/L (Wolff 2002) and a platelet count of more than >20 × 109/L (Teltschik et al. 2016) independent of platelet transfusion for at least 7 days. Collection of stem cells was done using apheresis machine (COBE SPECTRA). Complete peripheral blood counts using automated analyzers. Peripheral blood CD34 + cell counts and postapheresis CD34+ cell count using BD FACS CANTO II flow cytometer. To calculate postapheresis yield, the related CD34 count measured by flow cytometer was multiplied by the apheresis product volume and divided by the recipient’s body weight (kg). Number of CD34+ cells collected = (CD34 cell concentration in final product) × (final product volume). Results A total of 100 patients who underwent a total of 320 apheresis sessions were included in the study. There were 78 males and 22 females. We also found a significant correlation between preapheresis CD34 + cell count and postapheresis CD34 percentage on days 1, 2, and 3 of the apheresis sessions. In our study, to obtain more than 1.31 × 106 cells (median = 1.04, range: 0.15–4.70), an absolute count of pre apheresis CD34 + cells ≥14 cells would be necessary. A target of CD34 + cells ≥ 2 × 106/kg was obtained in majority of patients if a concentration of ≥25 CD34 + cells was present in postapheresis collection. Conclusion Compiling our results with the previous published data, we conclude that there is a strong correlation between preapheresis absolute CD34 + cell counts and postapheresis CD34 + cell count. Our study also suggests that the minimum absolute cell count of >10 cells/μL is required, to achieve a target of >2–5 × 106 cells for postapheresis yield.


2003 ◽  
Vol 34 (1) ◽  
pp. 16-19 ◽  
Author(s):  
Josefa Piedras-Ross ◽  
Eucario León-Rodrı́guez ◽  
Sergio Sánchez-Guerrero ◽  
Xavier López-Karpovitch

1993 ◽  
Vol 16 (5_suppl) ◽  
pp. 71-75 ◽  
Author(s):  
D.J. Richel ◽  
E. Van Der Wall ◽  
J. Slaper ◽  
E. Van Der Schoot ◽  
S. Rodenhuis

Peripheral blood stem cells can reconstitute bone marrow function after high-dose chemo-Zradiotherapy. We describe 44 patients related with a three-day course of chemotherapy, for hematopoietic stem cell mobilization, consisting of cyclophosphamide or ifosfamide and etoposide (malignant lymphoma and germ cell tumor) or a one-day course of 5-fluorouracil, epirubi-cin and cyclophosphamide (breast cancer), followed by the administration of recombinant human granulocyte colony-stimulating factor (G-CSF). Maximum numbers peripheral blood stem cells (PBSC) were recruited on day 9-10 of the G-CSF administration. The total number of PBSC cells harvested with median 3.6 leukaphereses was 46 x 104/kg (7.5-136) CFU-GM or 8 x 106/kg (0.7-25.0)CD34+ cells for patients with solid tumors and 26 (4.5-258) CFU-GM's or 6.1 (1-0-39.2) CD34+ cells for patients with malignant lymphomas. Thirty-five patients with malignant lymphomas or solid tumours received high-dose chemotherapy followed by bone marrow and PBSC infusion (n=8) or PBSC cell infusion alone (n=27). The recovery of granulocytes, platelets and reticulocytes after peripheral stem cell transplantation (-PSCT) in addition to or instead of bone marrow, was markedly accelerated compared with the infusion of BM alone. The accelerated haemopoietic recovery was associated with a reduction in platelet and red blood cell transfusion, reduction in fever periods and earlier discharge from hospital. PSCT is an important alternative to autologous bone marrow transplantation (ABMT). This transplantation technique may also allows application of multiple-cycle intensive chemotherapy.


Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4132-4138 ◽  
Author(s):  
WI Bensinger ◽  
CD Buckner ◽  
K Shannon-Dorcy ◽  
S Rowley ◽  
FR Appelbaum ◽  
...  

Abstract Sixteen patients with advanced hematologic malignancies were transplanted with HLA-identical allogeneic peripheral blood stem cells (PBSCs) that were selected for CD34+ cells by an avidin-biotin immunoadsorption technique. The median age of patients was 48 years (range, 37 to 67). Patients received 12.0 or 13.2 Gy of total body irradiation followed by 120 mg/kg of cyclophosphamide. Normal donors received 16 mg/kg of granulocyte-colony stimulating factor on days 1 to 6 followed by PBSC harvests on days 4 to 7. PBSC harvests were processed each day on a single avidin-blotin column containing an antibody to the CD34 antigen and processed cells were infused without cryopreservation daily for 4 consecutive days. Prophylaxis against graft-versus-host disease (GVHD) consisted of cyclosporine alone for 5 patients and CSA plus methotrexate for 11 patients. A median of 18.64 (6.74 to 34.97) x 10(8) CD34+ cells/kg patient body weight were collected from each donor. A median of 8.96 (2.62 to 17.34) x 10(8) CD34+ cells/kg patient body weight were recovered after avidin-biotin adsorption which represented a median CD34+ cell yield of 53% (18% to 77%) with a median purity of 62% (34% to 82%). There was a reduction in CD3+ cells from a median of 557.26 (227.73 to 677.77) x 106/kg to 0.73 x 10(4)/kg (0.40 to 3.65), in CD4+ cells from 351.72 (194.47 to 520.11) x 10(6)/kg to 0.40 (0.15 to 1.03) x 10(4)/kg and in CD8+ cells from 169.74 (53.34 to 325.83) x 10(6)/ kg to 0.32 (0.12 to 2.71) x 10(4)/kg representing a median 2.8 (2.19 to 3.14) log reduction in T cells. One patient died of infection on day 3 posttransplant and was unevaluable for recovery of neutrophils. The median day to recovery of 500 neutrophils/mL was 15 (8 to 26) in the remaining 15 patients. Six of 16 patients falled to achieve a platelet count of 20,000/mL before death on days 3 to 97 of transplant-related complications. The median day to achieving platelets of 20,000 mL in the remaining 10 patients was 11 (7 to 31). Eight of 16 patients (50%) died between 3 and 97 days posttransplant, 7 of transplant-related causes, and 1 of progressive disease. Grade 2–4 acute GVHD occurred in 12 out of 14 (86%) and grades 3–4 in 6 out of 14 (43%) evaluable patients. Six of 8 evaluable patients developed clinical chronic GVHD and 1 developed subclinical chronic GVHD. Bone marrow and/or peripheral blood chimerism studies in 12 evaluable patients showed 97% to 100% donor type in 11 patients with 1 patient in relapse showing 40% donor cells 60 to 90 days posttransplant. Four of 16 patients (25%) are alive and disease-free 312 to 576 days after transplant. There were no episodes of graft failure or rejection. This study shows that allogeneic transplantation using CD34+ selected PBSC results in prompt and sustained engraftment. CD34+ selection, as employed in this preliminary study, however, resulted in an apparently higher rate of acute and chronic GVHD. However, The sample size is quite small and precludes a more definitive conclusion regarding GVHD.


1994 ◽  
Vol 3 (2) ◽  
pp. 135-139
Author(s):  
ALISON RICE ◽  
JEAN-MICHEL BOIRON ◽  
CAROLINE BARBOT ◽  
MARYSE DUPOUY ◽  
NADINE DUBSOC-MARCHENAY ◽  
...  

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