Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia

Barrett, A. John; Horowitz, MM; Ash, RC; Atkinson, K; Rp, Gale; Goldman, JM; Downey, PJ Henslee-; Herzig, RH; Speck, B; Zwaan, F E

doi:10.1182/blood.v79.11.3067.bloodjournal79113067

Cited by 16 publications

(25 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, despite improvements in CR rates for Ph-positive ALL with newer treatments, alloSCT still is considered the mainstay of treatment for this patient subgroup. 16 However, this notion is being challenged. Several factors influence the outcome of patients who undergo alloSCT.…”

Section: Standard Chemotherapy and Allogeneic Stem Cell Transplantationmentioning

confidence: 99%

“…5,[8][9][10][11][12][13][14] Patients with Ph-positive ALL who received conventional chemotherapy reportedly had long-term survival rates of approximately 10%, 5,12,14 and only allogeneic stem cell transplantation (alloSCT) extended long-term survival in 38% to 65% of patients. [15][16][17][18][19][20][21] Outcomes for patients with Ph-positive ALL improved substantially with the introduction of the tyrosine kinase inhibitor (TKI) imatinib mesylate. Although imatinib monotherapy in previously treated patients with Ph-positive ALL produced only a modest, short-lived response, 22,23 imatinib combined with chemotherapeutic regimens has induced complete remissions (CRs) in almost every patient ($95%) with newly diagnosed Ph-positive ALL.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Philadelphia chromosome‐positive acute lymphoblastic leukemia

Lee

Thompson

Wang

et al. 2010

Cancer

107

View full text Add to dashboard Cite

The Philadelphia chromosome (Ph) is the most common cytogenetic abnormality associated with adult acute lymphoblastic leukemia (ALL). Before the advent of tyrosine kinase inhibitors (TKIs), Ph-positive ALL carried a dismal prognosis and was characterized by a poor response to most chemotherapy combinations, short remission durations, and poor survival rates. Outcomes for patients with Ph-positive ALL improved substantially with the introduction of TKIs, and the TKI imatinib induced complete remissions in >95% of patients with newly diagnosed Ph-positive ALL when it was combined with chemotherapy. However, imatinib resistance remains a problem in a substantial proportion of patients with Ph-positive ALL, and multiple molecular mechanisms that contribute to imatinib resistance have been identified. Second-generation TKIs (eg, dasatinib and nilotinib) have demonstrated promising efficacy in the treatment of imatinib-resistant, Ph-positive ALL. Future strategies for Ph-positive ALL include novel, molecularly targeted treatment modalities and further evaluations of TKIs in combination with established antileukemic agents. For this article, the authors reviewed past, current, and future treatment approaches for adult and elderly patients with Ph-positive ALL with a focus on TKIs and combined chemotherapeutic regimens. Cancer 2011;117:1583-94. V C 2010 American Cancer Society.KEYWORDS: acute lymphoblastic leukemia, imatinib resistance, Philadelphia chromosome, tyrosine kinase inhibitors.Age is an important determinant of prognosis and outcome for patients with acute lymphoblastic leukemia (ALL).Long-term survival rates approach 80% in children aged <5 years but decrease to approximately 50% to 60% in adolescents and young adults, to approximately 30% in adults ages 45 to 54 years, and rarely exceed 15% in older adults. [1][2][3] Prognostic changes that occur with increasing age may be attributable in part to age-dependent increases in unfavorable cytogenetic abnormalities. [4][5][6] The Philadelphia (Ph) chromosome is the most common cytogenetic abnormality associated with adult ALL. Although Ph-positive ALL occurs in only approximately 5% of patients with ALL aged <20 years, the incidence escalates to 33% in patients aged 40 years and is 49% in patients aged >40 years; the incidence decreases to 35% in patients aged >60 years. 4,7 Until recently, Ph-positive ALL carried a dismal prognosis in both children and adults. 5,[8][9][10][11][12][13][14] Patients with Ph-positive ALL who received conventional chemotherapy reportedly had long-term survival rates of approximately 10%, 5,12,14 and only allogeneic stem cell transplantation (alloSCT) extended long-term survival in 38% to 65% of patients. 15-21Outcomes for patients with Ph-positive ALL improved substantially with the introduction of the tyrosine kinase inhibitor (TKI) imatinib mesylate. Although imatinib monotherapy in previously treated patients with Ph-positive ALL produced only a modest, short-lived response, 22,23 imatinib combined with chemotherapeutic regimens...

show abstract

Section: Standard Chemotherapy and Allogeneic Stem Cell Transplantationmentioning

confidence: 99%

mentioning

confidence: 99%

Philadelphia chromosome‐positive acute lymphoblastic leukemia

Lee

Thompson

Wang

et al. 2010

Cancer

107

View full text Add to dashboard Cite

show abstract

“…More aggressive therapy protocols such as myeloablative chemotherapy with bone marrow transplantation (BMT) as consolidation of ®rst CR are the treatment of choice in younger patients. However, even with aggressive treatment recurrence of the disease is still a major problem and the probability of relapse (40±80%) is high (Barrett et al, 1992;Miyamura et al, 1992;Forman et al, 1987). The situation in patients receiving transplants in relapse is even worse Chao et al, (Clark et al, 1988;Schaefer-Rego et al, 1988;Hermans et al, 1987).…”

mentioning

confidence: 99%

Quantification of minimal residual disease in patients with BCR‐ABL‐positive acute lymphoblastic leukaemia using quantitative competitive polymerase chain reaction

Mitterbauer¹,

Németh²,

Wacha³

et al. 1999

Br J Haematol

View full text Add to dashboard Cite

Summary. We analysed 20 patients with BCR-ABL-positive acute lymphoblastic leukaemia (ALL) by quantitative competitive polymerase chain reaction (QC-PCR) to study the kinetics of the leukaemic clone. Consecutive samples of 16 patients (minor-bcr, n 10; major-bcr, n 6) were analysed after conventional chemotherapy and/or bone marrow transplantation (BMT). DNA competitor templates co-amplifying with either p210 or p190 BCR-ABL cDNA were used for quanti®cation of leukaemia-speci®c BCR-ABL mRNA. In all samples, total ABL transcripts were measured as internal control, and the percentage of BCR-ABL/ABL molecules was calculated. Following induction chemotherapy the number of BCR-ABL transcripts was reduced by a maximum of 2±3 logs. In most patients, additional chemotherapy did not lead to further reduction of BCR-ABL mRNA. In two patients, conventional chemotherapy plus autologous BMT in complete haematological remission resulted in a total reduction of the transcript level of more than 3 logs. In two other patients, allogeneic BMT caused a transient reduction of the BCR-ABL transcripts below the detection level of our method (<1 blast cell in 10 5 normal cells) for a period of 7 and 11 months, respectively. The achievement of PCR negativity did not guarantee sustained remission. Both patients relapsed and BCR-ABL transcript levels rose by more than 1 log prior to frank relapse. Our data demonstrate that quanti®cation of BCR-ABL mRNA allows the evaluation of the dynamics of the leukaemic clone and thus is valuable for the evaluation of minimal residual leukaemia following various therapies and the early detection of increasing BCR-ABL transcripts prior to relapse.

show abstract

“…There have been several reports regarding stem cell transplantation, but the outcome of the patients was variable. Some investigators reported relatively good results [13,14] whereas the others did not ®nd much bene®t in this treatment strategy [15,16]. One of the reasons for this discrepancy was that there are very few reports describing the outcome of a large series of patients.…”

Section: Discussionmentioning

confidence: 99%