Leukemic relapse in the central nervous system after allogeneic stem cell transplantation with complete remission in the bone marrow and donor‐type chimerism: Report of two cases

Ohashi, Haruhiko; Kato, Chiaki; Fukami, Shoko; Saito, Hidehiko; Hamaguchi, Motohiro

doi:10.1002/ajh.20333

Cited by 10 publications

(6 citation statements)

References 8 publications

(8 reference statements)

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“…The positive predictive value of declining donor chimerism for isolated extramedullary relapse was also the lower one (10%) in our study. Ohashi H et al [ 27 ] also suggest that the graft-versus-leukemia effects might not be as effective in the CNS as in the BM, even when complete T-lymphoid chimerism is achieved. So the observation of donor chimerism of the cases with isolated extramedullary relapse, without bone marrow recurrence, does not by itself constitute a risk factor for predicting relapse and should not be used to guide therapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

Donor Chimerism of B Cells and Nature Killer Cells Provides Useful Information to Predict Hematologic Relapse following Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2015

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In this study we investigated the correlation between donor chimerism status and disease relapse following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The chimerism of Fluorescence-activated cell sorter (FACS) sorted CD3+T lymphocytes of 153 cases, CD56+CD16+NK lymphocytes of 153 cases and CD19+B lymphocytes of 31 cases with acute B lymphoblastic leukemia (B-ALL) was analyzed post-transplant utilizing polymerase chain reaction amplification of short tandem repeats (PCR-STR). A total of 33 patients (33/153, 21.6%) had recurrent disease. The positive predictive values of declining donor chimerism for hematologic and isolated extramedullary relapse were 58.8% and 10% (P=0.018, Chi-Square). The positive predictive values of declining donor chimerism in BMB, BMT, BMNK and PBB for hematologic relapse were 11.6%, 0%, 0% and 0% under close monitoring in patients with B-ALL. Only the donor chimerism in BMB significantly decreased in the group with hematologic relapse as compared with the group without hematologic relapse (P=0.00, Independent-samples T test) in patients with B-ALL. The median drop of donor chimerism in PBT, BMT, PBNK and BMNK were 0%, 0%, 5.9% and 2.8% one or two weeks prior to hematologic relapse in patients with non-B-ALL. The donor chimerism in PBNK significantly decreased prior to hematologic relapse in the group with hematologic relapse as compared with the group without hematologic relapse (P=0.022, Independent-samples T test).These data suggest donor chimerism of BMB can be used to predict the occurrence of hematologic relapse in patients with B-ALL. Donor chimerism decrease in PBNKwas associated with a somewhat increased risk of hematologic relapse in patients with non-B-ALL. Therefore, our results reveal a more effective path to individually predict for hematologic relapse by dynamic monitoring different cell lineages in different disease.

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Section: Discussionmentioning

confidence: 99%

Donor Chimerism of B Cells and Nature Killer Cells Provides Useful Information to Predict Hematologic Relapse following Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2015

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“…1 Assessment of donor chimerism. Genomic DNA was extracted from the peripheral blood or bone marrow mononuclear cells and amplified by polymerase chain reaction with six sets of fluorescently labeled oligonucleotide primers specific for the nucleotides of short tandem repeat markers, as described previously [19]. Electrophoretic profiles of polymerase chain reaction products for three informative satellite makers are presented.…”

Section: Discussionmentioning

confidence: 99%

Donor cell leukemia after allogeneic peripheral blood stem cell transplantation: a case report and literature review

et al. 2008

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A 49-year-old male developed recurrent acute myeloid leukemia 27 months after allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA-identical brother. The immunophenotype of the blastic cell population was incompatible with that of the pre-transplant blast cells; a mutation in C/EBPA gene was found in the pre-transplant blast cells that was not present in the post-transplant blast cells, and short tandem repeat analysis of marrow cells, which included 71% blasts, showed complete donor chimera. Thus, this recipient developed donor cell leukemia (DCL). The donor was healthy when DCL developed in the recipient as well as before donation of the peripheral blood stem cells. Only five cases of DCL after PBSCT have been reported in the literature. As a mechanism for the development of DCL, a vigorous proliferative demand on the donor cells, which often correlates with a higher likelihood of replication error or mutation, has been proposed. Peripheral blood stem cells might have an advantage in that they are associated with a low incidence of DCL development because PBSCT recipients receive a higher total cell dose than recipients of bone marrow or cord blood cells.

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“…Granulocytes were collected by removing lysed red blood cells from the precipitate after incubation in ammonium chloride buffer. Following cell separation, DNA was extracted from the separated cells, and degrees of donor-recipient chimerism were analyzed with PCR of informative microsatellite regions [15,17,18]. Samples were prospectively analyzed on days 14, 28, 56, and 84.…”

Section: Chimerism Analysismentioning

confidence: 99%

Chimerism status after unrelated donor bone marrow transplantation with fludarabine-melphalan conditioning is affected by the melphalan dose and is predictive of relapse

Imahashi¹,

Ohashi

Terakura

et al. 2015

Ann Hematol

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Little is known regarding the chimerism status after reduced-intensity conditioning transplantation when bone marrow is used as a stem cell source. We prospectively analyzed lineage-specific chimerism and retrospectively evaluated clinical outcomes in 80 adult patients who underwent unrelated donor bone marrow transplantation (URBMT) with fludarabine plus melphalan (FM) as the conditioning regimen. Mixed donor chimerism (MDC) was seen in 43 and 10 % of patients at days 14 and 28, respectively. Melphalan at ≤130 mg/m(2) was associated with an increased incidence of MDC at day 28 (P = 0.03). Patients with MDC at day 14 showed a marginally increased risk of primary graft failure and a marginally decreased risk of graft-versus-host disease. In multivariate analysis, MDC at day 14 was associated with higher overall mortality (hazard ratio (HR) = 2.1; 95 % confidence interval (CI), 1.1-4.2; P = 0.04) and relapse rate (HR = 3.0; 95 % CI, 1.2-7.5; P = 0.02), but not with non-relapse mortality (HR = 1.8; 95 % CI, 0.70-4.6; P = 0.23). Thus, the FM regimen yields prompt complete donor chimerism after URBMT, but the melphalan dose significantly impacts the kinetics of chimerism. Chimerism status evaluation at day 14 may be instrumental in predicting relapse after URBMT with the FM regimen.

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Leukemic relapse in the central nervous system after allogeneic stem cell transplantation with complete remission in the bone marrow and donor‐type chimerism: Report of two cases

Cited by 10 publications

References 8 publications

Donor Chimerism of B Cells and Nature Killer Cells Provides Useful Information to Predict Hematologic Relapse following Allogeneic Hematopoietic Stem Cell Transplantation

Donor Chimerism of B Cells and Nature Killer Cells Provides Useful Information to Predict Hematologic Relapse following Allogeneic Hematopoietic Stem Cell Transplantation

Donor cell leukemia after allogeneic peripheral blood stem cell transplantation: a case report and literature review

Chimerism status after unrelated donor bone marrow transplantation with fludarabine-melphalan conditioning is affected by the melphalan dose and is predictive of relapse

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