Therapeutic Relevance of CD34 Cell Dose in Blood Cell Transplantation for Cancer Therapy

PURPOSE: To review recent advances in peripheral-blood progenitor-cell (PBPC) transplantation in order to define the optimal cell dose required for autologous and allogeneic transplantation. MATERIALS AND METHODS: A search of MEDLINE was conducted to identify relevant publications. Their bibliographies were also used to identify further articles and abstracts for critical review. RESULTS: The CD34+ cell content of a graft is regarded as an accurate predictor of engraftment success. Postchemotherapy autologous PBPC transplantation with ≥ 5 × 106 CD34+ cells/kg body weight leads to more rapid engraftment than does transplantation of lower cell doses. Further increases in transplant cell dose further accelerate platelet but not neutrophil engraftment. Evidence that long-term hematopoietic recovery may be more accurately predicted by the subpopulation of primitive progenitors transplanted suggests that the content of CD34+CD33− and long-term culture-initiating cells in cell collection samples may be important for predicting successful engraftment, particularly in patients with poor mobilization. Allogeneic transplantation has been limited by concerns regarding graft-versus-host disease and the use of hematopoietic growth factors in donors. The risk of graft rejection and engraftment failure after HLA-mismatched allogeneic transplantation may be overcome by intensive chemoradiotherapy and the infusion of large numbers of T cell–depleted hematopoietic stem cells. CONCLUSION: An optimal cell dose of ≥ 8 × 106 CD34+ cells/kg seems to be recommended for autologous PBPC transplantation. This dose facilitates the administration of scheduled chemotherapy on time and reduces the demand for other supportive therapies. A combination of growth factors may enable patients with poor mobilization to achieve a collection sufficient to allow transplantation. The optimum PBPC dose for allogeneic transplantation remains to be defined.

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Marrow- and spleen-seeding efficiencies of all murine hematopoietic stem cell subsets are decreased by preincubation with hematopoietic growth factors

Blood ◽

10.1182/blood.v85.9.2598.bloodjournal8592598 ◽

1995 ◽

Vol 85 (9) ◽

pp. 2598-2606 ◽

Cited By ~ 116

Author(s):

JC van der Loo ◽

RE Ploemacher

Keyword(s):

Stem Cell ◽

Growth Factors ◽

Growth Factor ◽

Hematopoietic Stem Cell ◽

Hematopoietic Growth Factors ◽

Hematopoietic Stem ◽

Murine Hematopoietic Stem Cell ◽

Seeding Efficiency

The cobblestone-area forming cell (CAFC) assay permits a direct measurement of the seeding of primitive and more mature murine hematopoietic stem cell subsets by comparing the number of CAFC in the original transplant with the number of CAFC retrieved from bone marrow (BM) and spleen after transplantation. We found no differences in seeding efficiency between the more mature and primitive CAFC subsets, nor between seeding efficiencies of stem cells from low-density (LD) fractions of normal and day-6 post-5-fluorouracil BM. The data show that 18% to 20% of all intravenously transplanted stem cell subsets seed to the BM, whereas 8% to 10% seed to the spleen. In addition, similar seeding efficiencies were found for day-12 spleen colony-forming unit (CFU-S-12) as was determined by retransplantation. Previously, it has been reported that a 2- to 3-hour preincubation of BM with interleukin-3 (IL-3) enhances the in vivo repopulating ability of a graft. To test whether hematopoietic growth factors affected this increased engraftment by enhancing the seeding of the transplanted marrow, we assessed the 16- to 18-hour seeding efficiency of short- and long-term in vivo repopulating stem cell subsets to BM and spleen using the CAFC assay, after preincubation with or without hematopoietic growth factors. A 2- to 3-hour preincubation with IL-3, or a combination of IL-3, IL-12, and steel factor, at 37 degrees C, led to a substantial decrease in seeding compared with control (which was kept on ice) of all hematopoietic subsets measured, both in spleen and BM. In concert with these data, the long-term in vivo repopulating ability of growth-factor incubated BM was also decreased when compared with control. In conclusion, we have been unable to observe a beneficial effect of growth factor preincubation on the repopulating ability of a graft.

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Autologous Transplantation for Older Adults with AML

Cancers ◽

10.3390/cancers10090340 ◽

2018 ◽

Vol 10 (9) ◽

pp. 340 ◽

Cited By ~ 4

Author(s):

Beatrice Mueller ◽

Katja Seipel ◽

Ulrike Bacher ◽

Thomas Pabst

Keyword(s):

Autologous Transplantation ◽

Allogeneic Transplantation ◽

Induction Treatment ◽

Term Survival ◽

Hematopoietic Stem ◽

Graft Versus Host ◽

Consolidation Treatment ◽

Autologous Hct

While the majority of patients with acute myeloid leukemia (AML) are above the age of 65 years at diagnosis, the outcome of older AML patients remains disappointing. Even if standard intensive chemotherapy induces morphologic complete remission (CR1), relapses in older AML patients are common leading to poor long-term survival outcomes. Since autologous hematopoietic stem cell transplantation (HCT) offers distinct anti-leukemic effectiveness while avoiding graft-versus-host disease associated with allogeneic transplantation, it represents an option for consolidation treatment in selected older AML patients. However, prospective studies in older AML patients assessing the benefit of autologous HCT compared to chemotherapy consolidation or allogeneic transplantation are lacking. Consequently, clinicians face the dilemma that there is considerable ambiguity on the most appropriate consolidation treatment for older AML patients in CR1. This review highlights the possible role of autologous HCT for consolidation in older AML patients reaching CR1 after induction treatment.

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Ex vivo expansion of human hematopoietic stem and progenitor cells

Blood ◽

10.1182/blood-2011-01-283606 ◽

2011 ◽

Vol 117 (23) ◽

pp. 6083-6090 ◽

Cited By ~ 187

Author(s):

Ann Dahlberg ◽

Colleen Delaney ◽

Irwin D. Bernstein

Keyword(s):

Stem Cell ◽

Growth Factors ◽

Notch Signaling ◽

Progenitor Cells ◽

Ex Vivo ◽

Ex Vivo Expansion ◽

Hematopoietic Growth Factors ◽

Self Renewal ◽

Hematopoietic Stem ◽

Stem And Progenitor Cells

AbstractDespite progress in our understanding of the growth factors that support the progressive maturation of the various cell lineages of the hematopoietic system, less is known about factors that govern the self-renewal of hematopoietic stem and progenitor cells (HSPCs), and our ability to expand human HSPC numbers ex vivo remains limited. Interest in stem cell expansion has been heightened by the increasing importance of HSCs in the treatment of both malignant and nonmalignant diseases, as well as their use in gene therapy. To date, most attempts to ex vivo expand HSPCs have used hematopoietic growth factors but have not achieved clinically relevant effects. More recent approaches, including our studies in which activation of the Notch signaling pathway has enabled a clinically relevant ex vivo expansion of HSPCs, have led to renewed interest in this arena. Here we briefly review early attempts at ex vivo expansion by cytokine stimulation followed by an examination of our studies investigating the role of Notch signaling in HSPC self-renewal. We will also review other recently developed approaches for ex vivo expansion, primarily focused on the more extensively studied cord blood–derived stem cell. Finally, we discuss some of the challenges still facing this field.

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Long-term complete remission of early hematological relapse after discontinuation of immunosuppressants following allogeneic transplantation for Sezary syndrome

Hematology Reports ◽

10.4081/hr.2018.7497 ◽

2018 ◽

Vol 10 (3) ◽

Cited By ~ 1

Author(s):

Hiroki Hosoi ◽

Kazuo Hatanaka ◽

Shogo Murata ◽

Toshiki Mushino ◽

Kodai Kuriyama ◽

...

Keyword(s):

Stem Cell ◽

Complete Remission ◽

Clinical Course ◽

Cell Lymphoma ◽

Allogeneic Transplantation ◽

Sézary Syndrome ◽

Sezary Syndrome ◽

Cutaneous T Cell Lymphoma ◽

Hematopoietic Stem

Sezary syndrome (SS) is a leukemic form of cutaneous T-cell lymphoma and is chemo-resistant. Allogeneic hematopoietic stem cell transplantation is a promising therapy for SS; however, relapse is common. Therapeutic options after relapse have not been established. We managed an SS patient with hematological relapse within one month after transplantation. After discontinuation of immunosuppressants, she achieved complete remission and remained relapse-free. The chimeric analyses of Tcells showed that the full recipient type became complete donor chimera after immunological symptoms. This clinical course suggested that discontinuation of immunosuppressants may result in a graftversus- tumor effect, leading to the eradication of lymphoma cells.

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A Case of Myeloproliferative Neoplasm with BCR-FGFR1 Rearrangement: Favorable Outcome after Haploidentical Allogeneic Transplantation

Case Reports in Hematology ◽

10.1155/2018/5724960 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Paola Villafuerte-Gutiérrez ◽

Montserrat López Rubio ◽

Pilar Herrera ◽

Eva Arranz

Keyword(s):

Kinase Inhibitors ◽

Fusion Gene ◽

Myeloproliferative Neoplasms ◽

Therapeutic Option ◽

Myeloproliferative Neoplasm ◽

Allogeneic Transplantation ◽

Term Survival ◽

Hematopoietic Stem ◽

Health Organization

Hematopoietic myeloproliferative neoplasms with FGFR1 rearrangement result in the 8p11 myeloproliferative syndrome that in the current Word Health Organization classification is designated as “myeloid and lymphoid neoplasm with FGFR1 abnormalities.” We report the case of a 66-year-old man who had clinical features that resembled chronic myeloid leukaemia (CML), but bone marrow cytogenetic and fluorescent in situ hybridization (FISH) studies showed t(8;22)(p11;q11) and BCR-FGFR1 fusion gene. He was initially managed with hydroxyurea, and given the aggressive nature of this disease, four months later, the patient underwent an allogeneic hematopoietic stem-cell transplantation (HSCT) from an HLA-haploidentical relative. Currently, HSCT may be the only therapeutic option for long-term survival at least until more efficacious tyrosine kinase inhibitors (TKIs) become available.

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“Influence of Body Composition Assessed by Computed Tomography on Mortality in Older Adults Undergoing Hematopoietic Stem Cell Transplantation”

10.21203/rs.3.rs-293335/v1 ◽

2021 ◽

Author(s):

Ludmila Koch ◽

Andrea Z Pereira ◽

Nelson Hamerschlak ◽

Adham do Amaral e Castro ◽

Adriano Tachibana ◽

...

Keyword(s):

Computed Tomography ◽

Body Composition ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Positive Association ◽

Allogeneic Transplantation ◽

Hematopoietic Stem ◽

Death Risk ◽

Graft Versus Host

Abstract Aim: The incidence of most hematologic malignancies increases with age. Hematopoietic stem cell transplantation (HSCT) provides a potentially life-prolonging or curative option for many patients in this scenario. Limited data is available on muscle mass and density assessed from CT-images on outcomes after HSCT. We aimed to evaluate the influence of body composition on morbidity and mortality in older adults undergoing (HSCT). Methods: Retrospective longitudinal study conducted with 50 patients ≥ 60 years undergoing HSCT at Hospital Israelita Albert Einstein, São Paulo. Body composition was assessed by chest computed tomography and treatment related mortality, graft versus host disease, neutrophil grafting, and overall survival were analyzed.Results: 148 HSCT patients were evaluated, 50 patients were eligible: 60% with autologous and 40% with allogeneic transplantation. Body mass index in patients was (female: 26.9 ± 4.7 kg/m2; 30.1± 4.9 kg/m2) - autologous and (female: 24.3 ± 5.15 kg/m2; male: 26.4 ± 2.0 kg/m2) - allogeneic. In autologous transplant group, we found a positive association between age and death risk with an increase of 63.5% in this risk (p=0.006) and also Karnofsky performance scale with decrease of 11.9% in death risk (p<0.001). A negative association between muscle radiodensity and death risk was observed in allogeneic transplantation patients with risk decrease of 20.1% (p = 0.032). We found a positive association between T4 muscle area and radiodensity with risk of acute graft versus host disease (p= 0.028). Conclusion: In population studied, body composition assessed by chest tomography showed the importance of radiodensity for better prognosis.

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Uva1 Phototherapy in the Management of Sclerodermatous Graft-Versus-Host Disease (Gvhd): a report of two cases / Uva1 fototerapija u lečenju sklerodermatoznog oblika hronične Gvhd: Prikaz dva slučaja

Serbian Journal of Dermatology and Venerology ◽

10.2478/v10249-011-0014-z ◽

2009 ◽

Vol 1 (4) ◽

pp. 147-152 ◽

Cited By ~ 1

Author(s):

Hiva Fassihi ◽

Kamran Iqbal ◽

Trish Garibaldinos ◽

Robert Sarkany ◽

Julia Scarisbrick ◽

...

Keyword(s):

Graft Versus Host Disease ◽

Skin Diseases ◽

Hematopoietic Stem ◽

Host Disease ◽

Allogeneic Hsct ◽

Graft Versus Host ◽

Uva1 Phototherapy ◽

Matched Sibling

Abstract Chronic graft-versus-host disease (GVHD) is a frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT). Approximately 10% of patients with GVHD develop sclerodermatous changes, which can cause significant morbidity and are often refractory to standard systemic immunosuppression. We present two cases of sclerodermatous GVHD. The first is a 39-year-old man, who had a matched sibling, undergoing allogeneic HSCT for severe aplastic anemia. The second patient is a 7-year-old boy, who had an allogeneic HSCT from his HLA-identical mother for acute myeloid leukemia (AML). Both patients presented with widespread sclerotic changes, resulting in joint contractures and significant functional difficulties. Studies have shown UVA1 phototherapy to be a promising and well tolerated treatment modality in patients with sclerotic skin diseases. Both of our patients were treated with UVA1, which resulted in a significant skin softening, improvement in joint mobility and quality of life. UVA1 appears to be an effective treatment for refractory sclerodermatous GVHD; however, long-term clinical studies in larger groups are needed to accurately evaluate its efficacy and safety.

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Growth factor treatment prior to low-dose total body irradiation increases donor cell engraftment after bone marrow transplantation in mice

Blood ◽

10.1182/blood.v100.1.312 ◽

2002 ◽

Vol 100 (1) ◽

pp. 312-317 ◽

Cited By ~ 6

Author(s):

Estelle J. K. Noach ◽

Albertina Ausema ◽

Jan H. Dillingh ◽

Bert Dontje ◽

Ellen Weersing ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Stem Cell ◽

Growth Factors ◽

Low Dose ◽

Donor Cell ◽

Hematopoietic Growth Factors ◽

Cell Engraftment ◽

Total Body

Abstract Low-toxicity conditioning regimens prior to bone marrow transplantation (BMT) are widely explored. We developed a new protocol using hematopoietic growth factors prior to low-dose total body irradiation (TBI) in recipients of autologous transplants to establish high levels of long-term donor cell engraftment. We hypothesized that treatment of recipient mice with growth factors would selectively deplete stem cells, resulting in successful long-term donor cell engraftment after transplantation. Recipient mice were treated for 1 or 7 days with growth factors (stem cell factor [SCF] plus interleukin 11 [IL-11], SCF plus Flt-3 ligand [FL], or granulocyte colony-stimulating factor [G-CSF]) prior to low-dose TBI (4 Gy). Donor cell chimerism was measured after transplantation of congenic bone marrow cells. High levels of donor cell engraftment were observed in recipients pretreated for 7 days with SCF plus IL-11 or SCF plus FL. Although 1-day pretreatments with these cytokines initially resulted in reduced donor cell engraftment, a continuous increase in time was observed, finally resulting in highly significantly increased levels of donor cell contribution. In contrast, G-CSF treatment showed no beneficial effects on long-term engraftment. In vitro stem cell assays demonstrated the effect of cytokine treatment on stem cell numbers. Donor cell engraftment and number of remaining recipient stem cells after TBI were strongly inversely correlated, except for groups treated for 1 day with SCF plus IL-11 or SCF plus FL. We conclude that long-term donor cell engraftment can be strongly augmented by treatment of recipient mice prior to low-dose TBI with hematopoietic growth factors that act on primitive cells.

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Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants

Blood ◽

10.1182/blood.v95.12.3683 ◽

2000 ◽

Vol 95 (12) ◽

pp. 3683-3686 ◽

Cited By ~ 99

Author(s):

Samar Kulkarni ◽

Ray Powles ◽

Jennie Treleaven ◽

Unell Riley ◽

Seema Singhal ◽

...

Keyword(s):

Graft Versus Host Disease ◽

Chronic Gvhd ◽

Pneumococcal Infection ◽

Pneumococcal Infections ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host ◽

Increased Risk ◽

Penicillin Prophylaxis

Abstract Incidences of and risk factors for Streptococcus pneumoniaesepsis (SPS) after hematopoietic stem cell transplantation were analyzed in 1329 patients treated at a single center between 1973 and 1997. SPS developed in 31 patients a median of 10 months after transplantation (range, 3 to 187 months). The infection was fatal in 7 patients. The probability of SPS developing at 5 and 10 years was 4% and 6%, respectively. Age, sex, diagnosis, and graft versus host disease (GVHD) prophylaxis did not influence the development of SPS. Allogeneic transplantation (10-year probability, 7% vs 3% for nonallogeneic transplants; P = .03) and chronic GVHD (10-year probability, 14% vs 4%; P = .002) were associated with significantly higher risk for SPS. All the episodes of SPS were seen in patients who had undergone allograft or total body irradiation (TBI) (31 of 1202 vs 0 of 127;P = .07). Eight patients were taking regular penicillin prophylaxis at the time of SPS, whereas 23 were not taking any prophylaxis. None of the 7 patients with fatal infections was taking prophylaxis for Pneumococcus. Pneumococcal bacteremia was associated with higher incidences of mortality (6 of 15 vs 1 of 16;P = .04). We conclude that there is a significant long-term risk for pneumococcal infection in patients who have undergone allograft transplantation, especially those with chronic GVHD. Patients who have undergone autograft transplantation after TBI-containing regimens also appear to be at increased risk. These patients should receive lifelong pneumococcus prophylaxis. Consistent with increasing resistance to penicillin, penicillin prophylaxis does not universally prevent SPS, though it may protect against fatal infections. Further studies are required to determine the optimum prophylactic strategy in patients at risk.

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