In patients with BCR-ABL-positive ALL in CR peripheral blood contains less residual disease than bone marrow: Implications for autologous BMT

Martin, Hans; Atta, Johannes; Bruecher, J.; Elsner, Stefanie; Schardt, Christof; Stadler, Michael; Melchner, Harald von; Hoelzer, Dieter

doi:10.1007/bf01715137

Cited by 27 publications

(20 citation statements)

References 16 publications

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“…29 Similarly, Martin et al have found that Bcr-Abl levels were about 35-fold lower in PB than in BM of 6 patients with Ph ϩ ALL. 30 However, others observed similar levels in PB and in BM. 31,32 Potential causes of the difference in MRD levels and kinetics between PB and BM that are associated with imatinib include redistribution of the blasts and different susceptibility to this agent (eg, due to distinct proliferative properties of leukemic blast cells in these compartments).…”

Section: Discussionmentioning

confidence: 88%

Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Abl–positive acute lymphoblastic leukemia with the Abl-tyrosine kinase inhibitor imatinib (STI571)

Scheuring

Pfeifer

Waßmann

et al. 2003

Blood

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The Abl kinase inhibitor imatinib mesylate (STI571) has significant and rapid antileukemic activity in Philadelphia chromosome/Bcr-Abl-positive acute lymphoblastic leukemia (Ph ؉ ALL) but such activity is usually of short duration except for a small proportion of patients. To determine the prognostic significance of early Bcr-Abl levels and changes in peripheral blood (PB) and bone marrow (BM), serial samples of 56 patients with relapsed or refractory Ph ؉ ALL treated in phase 2 trials of imatinib were analyzed by quantitative polymerase chain reaction (PCR). Imatinib induced a complete hematologic response (CHR) or complete marrow response (marrow-CR) in 40 patients (good responders) and a partial (n ‫؍‬ 2) or no (n ‫؍‬ 14) remission in the remaining patients (poor responders). Compared with baseline, the median Bcr-Abl/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratios decreased significantly in PB by 2.65, 2.64, and 3.11 log steps after 2 weeks, 4 weeks, and at the time of best response, respectively. In BM, the decline of median BcrAbl/GAPDH was 0.75, 1.37, and 2.78 logs, respectively. Thus, Bcr-Abl levels decreased more rapidly in PB than in BM (median time to best level 31 vs 39 days). Low Bcr-Abl/GAPDH ratios below 10 ؊4 in PB and below 10 ؊2 in BM after 2 weeks were significantly associated with good responses after 4 weeks. Moreover, BcrAbl levels (< 10 ؊2 ) in BM of good responders after 4 weeks discriminated between 2 groups of patients with significantly different median time to progression (

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Section: Discussionmentioning

confidence: 88%

Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Abl–positive acute lymphoblastic leukemia with the Abl-tyrosine kinase inhibitor imatinib (STI571)

Scheuring

Pfeifer

Waßmann

et al. 2003

Blood

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“…We previously found median 1.5 log lower RT-PCR titers in unmobilized peripheral blood as compared to bone marrow in nine paired samples from remission patients 26 and hypothesized that PBSC grafts might be superior to BM grafts due to a significantly lower level of residual leukemia. In another small series of four G-CSF-mobilized leukapheresis samples there was a trend for even lower RT-PCR titers.…”

Section: Discussionmentioning

confidence: 99%

Purging in BCR-ABL-positive acute lymphoblastic leukemia using immunomagnetic beads: comparison of residual leukemia and purging efficiency in bone marrow vs peripheral blood stem cells by semiquantitative polymerase chain reaction

Atta

Fauth

et al. 2000

Bone Marrow Transplant

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Summary:Twenty autologous bone marrow (BM) and 25 peripheral blood stem cell (PBSC) grafts were collected from a total of 40 consecutive patients with BCR-ABL + acute lymphoblastic leukemia (ALL) in first (n = 37) or second (n = 3) complete morphological remission and subsequently purged with a cocktail of anti-CD19, -CD10, AB4 MoAbs and immunomagnetic beads (IMB). Residual BCR-ABL-positive cells before purging were detected in 19 of 20 BM grafts at a median of 4 (range 0-6) logs and in 17 of 25 evaluable PBSC grafts at a median of 1 (range 0-3) log above the limit of detection assessed by a semiquantitative limiting log 10 -dilution RT-PCR (P Ͻ 0.0001). IMB purging depleted a median of 2.5 (range 1-4) log of residual BCR-ABL + cells from BM and a median of 1 (range 0-2) log from PBSC grafts, achieving RT-PCR negativity in 1/20 BM and 12/25 PBSC grafts after purging. Cell recoveries were 62% and 86% (P Ͻ 0.0001) of MNC and 74% and 97% (P = 0.065) of CD34 + cells after BM and PBSC purging, respectively. BM purging was superior using the triple MoAb cocktail which depleted 2.64 ؎ 0.4 log (n = 14) compared to 1.6 ؎ 0.4 log (n = 5) using the MoAb cocktail not including AB4 (P = 0.02). We conclude that unpurged BM grafts contain 2-3 log more residual BCR-ABL + cells than unpurged PBSC grafts and that purging efficacy is superior in BM compared to PBSC grafts, but median titers in purged BM grafts still exceed those in purged PBSC grafts. Bone Marrow Transplantation (2000) 25, 97-104.

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“…Several studies have proven that the levels of MRD in peripheral blood and bone marrow correlate well in T-ALL, but that the correlation is weak in B-cell precursor ALL, with a generally lower peripheral blood MRD. [9][10][11][12][13] Surprisingly, only a few reports have explored the prognostic impact of MRD in peripheral blood, although sampling peripheral blood is far more comfortable for patients and easier for clinicians than aspirating bone marrow. Brisco et al…”

Section: Introductionmentioning

confidence: 99%

Minimal residual disease in peripheral blood at day 15 identifies a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with superior prognosis

Volejnikova¹,

Mejstříková²,

Valova³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundMost minimal residual disease-directed treatment interventions in current treatment protocols for acute lymphoblastic leukemia are based on bone marrow testing, which is a consequence of previous studies showing the superiority of bone marrow over peripheral blood as an investigational material. Those studies typically did not explore the prognostic impact of peripheral blood involvement and lacked samples from very early time points of induction. Design and MethodsIn this study, we employed real-time quantitative polymerase chain reaction analysis to examine minimal residual disease in 398 pairs of blood and bone marrow follow-up samples taken from 95 children with B-cell precursor acute lymphoblastic leukemia treated with the ALL IC-BFM 2002 protocol. ResultsWe confirmed the previously published poor correlation between minimal residual disease in blood and marrow at early treatment time points, with levels in bone marrow being higher than in blood in most samples (median 7.9-fold, range 0.04-8,293-fold). A greater involvement of peripheral blood at diagnosis was associated with a higher white blood cell count at diagnosis (P=0.003) and with enlargement of the spleen (P=0.0004) and liver (P=0.05). At day 15, a level of minimal residual disease in blood lower than 10 -4 was associated with an excellent 5-year relapse-free survival in 78 investigated patients (100% versus 69±7%; P=0.0003). Subgroups defined by the level of minimal residual disease in blood at day 15 (high-risk: ≥10 ) partially correlated with bone marrowbased stratification described previously, but the risk groups did not match completely. No other time point analyses were predictive of outcome in peripheral blood, except for a weak association at day 8. ConclusionsMinimal residual disease in peripheral blood at day 15 identified a large group of patients with an excellent prognosis and added prognostic information to the risk stratification based on minimal residual disease at day 33 and week 12.Key words: acute lymphoblastic leukemia, peripheral blood, minimal residual disease, day 15, childhood.Citation: Volejnikova J, Mejstrikova E, Valova T, Reznickova L, Hodonska L, Mihal V, Sterba J, Jabali Y, Prochazkova D, Blazek B, Hak J, Cerna Z, Hrusak O, Stary J, Trka J, and Fronkova E. Minimal residual disease in peripheral blood at day 15 identifies a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with superior prognosis. Haematologica 2011;96(12):1815-1821. doi:10.3324/haematol.2011 This is an open-access paper. Minimal residual disease in peripheral blood at day 15 identifies a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with superior prognosis

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In patients with BCR-ABL-positive ALL in CR peripheral blood contains less residual disease than bone marrow: Implications for autologous BMT

Cited by 27 publications

References 16 publications

Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Abl–positive acute lymphoblastic leukemia with the Abl-tyrosine kinase inhibitor imatinib (STI571)

Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Abl–positive acute lymphoblastic leukemia with the Abl-tyrosine kinase inhibitor imatinib (STI571)

Purging in BCR-ABL-positive acute lymphoblastic leukemia using immunomagnetic beads: comparison of residual leukemia and purging efficiency in bone marrow vs peripheral blood stem cells by semiquantitative polymerase chain reaction

Minimal residual disease in peripheral blood at day 15 identifies a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with superior prognosis

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