scholarly journals Long-Term Survival after Transplantation of Unrelated Donor Peripheral Blood or Bone Marrow Hematopoietic Cells for Hematologic Malignancy

2015 ◽  
Vol 21 (1) ◽  
pp. 55-59 ◽  
Author(s):  
Mary Eapen ◽  
Brent R. Logan ◽  
Fredrick R. Appelbaum ◽  
Joseph H. Antin ◽  
Claudio Anasetti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Hematologic Malignancy ◽  
Hematopoietic Cells ◽  
Unrelated Donor ◽  
Term Survival ◽  
Long Term Survival

scholarly journals Engraftment and Long-Term Survival at Low Burden of Leukemic Blasts from Primary MRD+ Human Bone Marrow in a Xenotransplant Setting

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1730-1730
Author(s):  
Nina Rolf ◽  
Angela Tsang ◽  
Abbas Fotovati ◽  
Arnawaz Bashir ◽  
Patrice Eydoux ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Human Cell ◽  
Peripheral Blood ◽  
Human Cells ◽  
Recipient Mouse ◽  
Term Survival ◽  
Long Term Survival ◽  
Nsg Mice ◽  
Overt Leukemia

Abstract Minimal residual disease (MRD) in bone marrow (BM) at the end of induction or re-induction chemotherapy is a critical prognostic factor for long-term survival of children with acute lymphoblastic leukemia (ALL). The presence of submicroscopic disease is a significant predictor of leukemia relapse, such that MRD positivity (0.01% to 5%) informs risk-adapted treatment intensification following induction. As most cases of relapsed ALL involve a clone that existed as a minor subclone at diagnosis, strategies that enable characterization of the leukemic blasts surviving at the end of induction could further influence treatment selection; however, the low numbers of leukemic blasts in an MRD sample makes evaluation of their sensitivity to chemotherapy or other treatment modalities challenging. Immune-deficient NOD-scid/IL2Rγc null(NSG) mice are highly receptive to the engraftment and expansion of ALL blasts from diagnostic and relapse samples. However, little is known about the reproducibility of this approach for the small numbers of leukemic cells in primary MRD+ BM samples. To investigate the fate of MRD blasts following xenografting, MRD+ mononuclear cells from BM samples from 6 children with B-ALL in first (n=3) or subsequent remissions (n=3), with a median MRD level of 0.65% (range: 0.08-4.3%), were adoptively transferred into NSG mice by tail vein injection. Engraftment and expansion were monitored by regular flow cytometric evaluation of peripheral blood for human CD45 expressing cells, and mice were euthanized at onset of leukemia (human cell count > 15,000/ul) or after up to 1 year on study. BM, spleen and peripheral blood were harvested at time of death, and cells immunophenotyped with the identical 10-colour flow panel following a COG-validated, clinical MRD diagnostic algorithm. Human cell engraftment was confirmed in all recipient mice. Recipients of two of the MRD samples progressed to frank leukemia: one mouse injected with an MRD burden of 4.3% presented with an elevated WBC after 6 months and a blast count of 67% in spleen, while another mouse euthanized one year after injection of a 0.16% MRD+ sample had 75% blasts in BM that comprised both leukemic subclones present in the original MRD sample. Of the two MRD samples, only the former was from a patient that subsequently relapsed. Although all other recipient mice continued to show fluctuating, but sustained low levels of peripheral human cells (<5% of human CD45+ cells among mouse CD45+ peripheral blood cells), none progressed to overt leukemia. At sacrifice (range: 179-390 days, median 260 days), all remaining recipient mice were confirmed to contain leukemic blasts at low burden in BM, ranging from 0.001% to 0.675% of immunophenotypically verified human leukemic blasts in 1-1.5 million of total cells. An in-depth comparison of primary MRD samples and the mouse engrafted blasts revealed that similar immunophenotypic blast populations identified in the patient MRD sample were sustained for as long as 1 year in NSG mice; in several mice there was evidence of maintenance of two to three distinct immunophenotypic subclones that were present at day 0 and/or day 29 in the patient. Furthermore, in all recipient mice the vast majority of human cells were phenotypically confirmed to be blasts and no significant amount of normal human hematopoiesis following injection of the MRD samples was detected. This study demonstrates that heterogeneous leukemic cell populations from primary MRD+ BM samples can be successfully engrafted and sustained in NSG mice and that, in at least a subset of recipients, these blasts can progress to overt leukemia. Notably, one MRD-recipient mouse presented with leukemia prior to any progression in the patient, raising the possibility that this approach could be used to characterize potential relapse clones ahead of their clinical appearance. Furthermore, the sustained presence of leukemic blasts in all non-progressing recipients for as long as 1 year demonstrates the reproducibility of this approach for generating a stable, low level leukemia burden that resembles the MRD state. Such a setting may enable the evaluation of therapeutic interventions for efficacy against the residual blasts that will give rise to relapse in the patient. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Colony-Stimulating Factor 3 Receptor M696T Mutated in a Patient with Ph+ Acute Lymphoblastic Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Xin Chen ◽  
Bichen Wang ◽  
Aiming Pang ◽  
Erlie Jiang ◽  
Yajing Chu ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
Unrelated Donor ◽  
Colony Stimulating Factor ◽  
Term Survival ◽  
Long Term Survival ◽  
Tumor Transformation ◽  
Stimulating Factor

Purpose: Colony-stimulating factor 3 receptor (CSF3R) mutations have been identified in a variety of myeloid disorders, such as severe congenital neutropenia (SCN), chronic neutrophilic leukemia (CNL), myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and atypical chronic myelogenous leukemia (aCML). Although CSF3R point mutations (e.g., T618I) are emerging as key players in CNL/aCML, the significance of rarer CSF3R mutations is unknown. We report a case of philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) with the M696T mutation in CSF3R gene and assess the pathogenicity of the CSF3R M696T mutation in Ph+ ALL. Experimental Design: Here we report on a 32-year-old female who presented with asthenia. The initial hematological workup revealed white blood cell (WBC) count of 97 x 109/L (normal range 4-10 x 109/L). There was 84% prolymphocyte in the bone marrow. The immunophenotype of the blasts as judged from flow cytometry was in accordance with a B-ALL. The fusion gene for BCR-ABL P210 was positive. Hot mutation closely related to diseases was: CSF3R (nucleotide change c.2087 T&gt;C, amino acid change p.M696T, mutation frequency 50.4%). Cytogenetic analysis showed 46, XX, t (9;22) (q34;q11). The patient was diagnosed as Ph+ ALL with the CSF3R M696T mutation and achieved Long-term survival after unrelated donor hematopoietic stem cell transplantation. Meanwhile we performed a series of experiments using murine interleukin 3 (IL-3)-dependent Ba/F3 cell line to evaluate the transforming capacity of the CSF3R M696T mutation. The phosphorylation of STAT3 was analyzed by G-CSF dependence assays and immunoblot analysis to evaluate the CSF3R M696T mutation contribution to the tumor transformation ability of Ba/F3 cells. Results: This patient achieved complete remission with chemotherapy in combination with tyrosine kinase inhibitor (TKI) and long-term survival by unrelated donor transplantation. We confirmed the presence of a CSF3R M696T germline mutation in this patient, and the mutation was inherited from her mother. The experiments in vitro result showed the CSF3R M696T mutation harbors marginal contribution to the tumor transformation ability of Ba/F3 cells. CSF3R M696T mutation was neutral in tumor transformation ability. Conclusions: We believe that TKI is still effective in patients with the CSF3R M696T mutation in Ph+ ALL. Donor with CSF3R M696T mutation might still be selected. Disclosures No relevant conflicts of interest to declare.

scholarly journals Hematopoiesis in Long-Term Survival Following Supralethal Irradiation and Bone Marrow Transplantation in Dogs

Blood ◽  
1968 ◽  
Vol 32 (6) ◽  
pp. 895-907 ◽  
Author(s):  
J. L. CHERTKOV ◽  
M. N. NOVIKOVA ◽  
N. M. NEMENOVA ◽  
V. N. MALANINA
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Term Survival ◽  
Long Term Survival

High-Risk Neuroblastoma Treated With Tandem Autologous Peripheral-Blood Stem Cell–Supported Transplantation: Long-Term Survival Update

2006 ◽  
Vol 24 (18) ◽  
pp. 2891-2896 ◽  
Author(s):  
Rani E. George ◽  
Shuli Li ◽  
Cheryl Medeiros-Nancarrow ◽  
Donna Neuberg ◽  
Karen Marcus ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Blood Stem Cell ◽  
Term Survival ◽  
Long Term Survival ◽  
Stem Cell Rescue ◽  
Cns Relapse

Purpose To provide an update on long-term survival of patients with high-risk neuroblastoma treated with tandem cycles of myeloablative therapy and peripheral-blood stem-cell rescue (PBSCR). Patients and Methods Ninety-seven patients with high-risk neuroblastoma were treated between 1994 and 2002. Patients underwent induction therapy with five cycles of standard agents, resection of the primary tumor and local radiation, and two consecutive courses of myeloablative therapy (including total-body irradiation) with PBSCR. Results Fifty-one patients have experienced relapse or died. Median follow-up time among the 46 patients who remain alive without progression is 5.6 years (range, 15.1 months to 9.9 years). Progression-free survival (PFS) rate at 5 years from diagnosis was 47% (95% CI, 36% to 56%), and PFS rate at 7 years was 45% (95% CI, 34% to 55%). Overall survival rate was 60% (95% CI, 48% to 69%) and 53% (95% CI, 40% to 64%) at 5 and 7 years, respectively. The 5- and 7- year PFS rates from time of first transplantation for 82 patients who completed both transplants were 54% (95% CI, 42% to 64%) and 52% (95% CI, 40% to 63%), respectively. Five patients died from treatment-related toxicity after tandem transplantation. Relapse occurred in 37 (42%) of 89 patients, mainly within 3 years of transplantation and primarily in diffuse osseous sites. No primary CNS relapse or secondary leukemia was seen. One patient developed synovial cell sarcoma 8 years after therapy. Conclusion High-dose therapy with tandem autologous stem-cell rescue is effective for treating high-risk neuroblastoma, with encouraging long-term survival. CNS relapse and secondary malignancies are rare after this therapy.

Busulfan/cyclophosphamide as conditioning regimen for allogeneic bone marrow transplantation for myelodysplasia.

1995 ◽  
Vol 13 (12) ◽  
pp. 2973-2979 ◽  
Author(s):  
M R O'Donnell ◽  
G D Long ◽  
P M Parker ◽  
J Niland ◽  
A Nademanee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Conditioning Regimen ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Term Survival ◽  
Long Term Survival

PURPOSE A non-radiation-containing regimen of busulfan and cyclophosphamide (BU/CY) was evaluated for toxicity, relapse, and long-term survival in patients who received allogeneic bone marrow transplantation (BMT) for myelodysplasia (MDS). PATIENTS AND METHODS Thirty-eight patients with MDS, including eight with therapy-related MDS, were prepared for BMT using BU/CY. RESULTS Fourteen patients remain in first remission 18 to 60 months posttransplant. Five patients relapsed after BMT, and four of these patients died. Eight additional patients died of acute or chronic graft-versus-host disease (GVHD), and 11 died of regimen-related toxicity, primarily systemic mycoses. Overall survival rate at 2 years was 45% (95% confidence interval [CI], 0.30 to 0.61), with a 24% probability of relapse (95% CI, 0.10 to 0.49). Regimen-related toxicity was manifested primarily as hepatic dysfunction in 72% of patients, with 16% developing overt venoocclusive disease (VOD). CONCLUSION Non-radiation-containing preparative regimens offer long-term survival in allogeneic BMT for MDS that is comparable to that of radiation-containing regimens, and are useful in patients with therapy-related MDS. Monitoring BU levels may reduce regimen-related mortality and improve survival.

Long-Term Survival and Late Deaths after Allogeneic Bone Marrow Transplantation

1999 ◽  
Vol 341 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Gérard Socié ◽  
Judith Veum Stone ◽  
John R. Wingard ◽  
Daniel Weisdorf ◽  
P. Jean Henslee-Downey ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Term Survival ◽  
Long Term Survival
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