scholarly journals Marrow Transplants From Unrelated Donors for Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1410-1414 ◽  
Author(s):  
Jorge Sierra ◽  
Jerry Radich ◽  
John A. Hansen ◽  
Paul J. Martin ◽  
Effie W. Petersdorf ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Early Stage ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Unrelated Donor ◽  
Effective Treatment Option ◽  
Patients At Risk ◽  
Unrelated Donors ◽  
First Relapse ◽  
Philadelphia Chromosome Positive

Transplantation of marrow from unrelated donors was investigated in patients with Philadelphia chromosome-positive (Ph1+) acute lymphoblastic leukemia (ALL) who lacked a suitable family donor. Eighteen patients underwent transplantation at our center between 1988 and 1995. The median patient age was 25 years (range, 1.7 to 51 years). Seven patients were in first complete remission, 1 in second remission, 3 in first relapse, and the remaining 7 had more advanced or chemotherapy refractory leukemia at transplant. All patients were conditioned with cyclophosphamide and total body irradiation followed by marrow transplants from closely HLA-matched, unrelated volunteers. Posttransplant graft-versus-host disease (GVHD) prophylaxis included methotrexate with either cyclosporine or FK506. Graft failure was not observed. Severe (grades III-IV) GVHD appeared in 6 of 17 evaluable patients and chronic extensive GVHD in 7 of 13 patients at risk. Five patients had recurrent ALL after transplantation and another 4 died from causes other than leukemia. Six patients transplanted in first remission, 2 in first relapse, and 1 in second remission remain alive and leukemia-free at a median follow-up of 17 months (range, 9 to 73 months). The probability of leukemia-free survival at 2 years is 49% ± 12%. These data indicate that unrelated donor marrow transplantation is an effective treatment option for patients with early stage Ph1+ ALL without a family match and suggest that in such patients an unrelated donor search should be initiated as soon as possible after diagnosis.

scholarly journals Marrow Transplants From Unrelated Donors for Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1410-1414 ◽  
Author(s):  
Jorge Sierra ◽  
Jerry Radich ◽  
John A. Hansen ◽  
Paul J. Martin ◽  
Effie W. Petersdorf ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Early Stage ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Unrelated Donor ◽  
Effective Treatment Option ◽  
Patients At Risk ◽  
Unrelated Donors ◽  
First Relapse ◽  
Philadelphia Chromosome Positive

Abstract Transplantation of marrow from unrelated donors was investigated in patients with Philadelphia chromosome-positive (Ph1+) acute lymphoblastic leukemia (ALL) who lacked a suitable family donor. Eighteen patients underwent transplantation at our center between 1988 and 1995. The median patient age was 25 years (range, 1.7 to 51 years). Seven patients were in first complete remission, 1 in second remission, 3 in first relapse, and the remaining 7 had more advanced or chemotherapy refractory leukemia at transplant. All patients were conditioned with cyclophosphamide and total body irradiation followed by marrow transplants from closely HLA-matched, unrelated volunteers. Posttransplant graft-versus-host disease (GVHD) prophylaxis included methotrexate with either cyclosporine or FK506. Graft failure was not observed. Severe (grades III-IV) GVHD appeared in 6 of 17 evaluable patients and chronic extensive GVHD in 7 of 13 patients at risk. Five patients had recurrent ALL after transplantation and another 4 died from causes other than leukemia. Six patients transplanted in first remission, 2 in first relapse, and 1 in second remission remain alive and leukemia-free at a median follow-up of 17 months (range, 9 to 73 months). The probability of leukemia-free survival at 2 years is 49% ± 12%. These data indicate that unrelated donor marrow transplantation is an effective treatment option for patients with early stage Ph1+ ALL without a family match and suggest that in such patients an unrelated donor search should be initiated as soon as possible after diagnosis.

Curcumin Potentiates Antitumor Activity of Imatinib Via Inhibition of the AKT/mTOR Signaling Pathway and Down-Regulation of Bcr-Abl Gene in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3559-3559
Author(s):  
Yuping Gong ◽  
Yong Guo ◽  
Ting Niu
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Kinase Inhibitor ◽  
Conflicts Of Interest ◽  
Early Stage ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Mtor Signaling ◽  
Perennial Herb ◽  
Apoptosis Protein ◽  
Philadelphia Chromosome Positive

Abstract Abstract 3559 Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) is triggered by constitutively activated BCR-ABL and SRC family tyrosine kinases. They interact each other, then activate downstream growth-signaling pathways including Raf/MEK/ERK,Akt/mTOR and STAT5 pathways. The BCR-ABL tyrosine kinase inhibitor imatinib is the standard treatment for Ph+ leukemia. However, response rate of Ph+ ALL to imatinib is low, relapse is frequent and quick. Studies have documented the potential anti-tumor activities of curcumin, a yellow colored polyphenol from the perennial herb Curcuma longa. However, whether curcumin can be used in the therapy for Ph+ALL remains obscure. Here, we reported that curcumin induced autophagic cell death by activating RAF/MEK/ERK pathway in early stage of the 24-hour exposure course, later induced apoptosis by inhibiting AKT/mTOR, ABL/STAT5 signalings, down-regulating expression of bcr/abl gene and Bcl2 anti-apoptosis protein, and up-regulating the expression of pro-apoptosis protein BAX in Ph+ALL cell line SUP-B15. Furthermore, we found curcumin exerted synergetic anti-leukemia effect with imatinib by inhibiting imatinib-mediated up-regulation of the activation of AKT/mTOR signaling and down-regulating expression of bcr/abl gene. It is worth noting that curcumin provide advantages over dexmethasone as to synergetic anti-leukemia effect with imatinib because dexmethasone improved the imatinib-mediated up-regulation of the activation of AKT/mTOR/P70S6 signaling. In primary samples from Ph+ALL patients, curcumin inhibit growth signaling not only in newly-diagnosised patient but also in imatinib-resistant patient. Moreover, curcumin effectively exhibited anti-leukemia efficacy and synergetic anti-leukemia effect with imatinib in Ph+ALL mouse models. These results demonstrate that curcumin may be a promising agent for the treatment of patients with Ph+ ALL, and curcumin might be particularly effective when used with current induction regimens consisting of imatinib with or without chemotherapy for treating Ph+ ALL. [Grant Support:National Natural Science Foundation of China (No.30770912), Foundation of the Science & Technology Department of Sichuan Province (No.2008SZ0017)]. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993

Blood ◽  
2009 ◽  
Vol 113 (19) ◽  
pp. 4489-4496 ◽  
Author(s):  
Adele K. Fielding ◽  
Jacob M. Rowe ◽  
Susan M. Richards ◽  
Georgina Buck ◽  
Anthony V. Moorman ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Prospective Trial ◽  
Philadelphia Chromosome ◽  
Outcome Data ◽  
White Blood Count ◽  
Unrelated Donor ◽  
No Donor ◽  
Hematopoietic Stem ◽  
Philadelphia Chromosome Positive

Abstract Prospective data on the value of allogeneic hematopoietic stem cell transplantation (alloHSCT) in Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) are limited. The UKALLXII/ECOG 2993 study evaluated the outcome of assigning alloHSCT with a sibling (sib) or matched unrelated donor (MUD) to patients younger than 55 years of age achieving complete remission (CR). The CR rate of 267 patients, median age 40, was 82%. Twenty-eight percent of patients proceeded to alloHSCT in first CR. Age older than 55 years or a pre-HSCT event were the most common reasons for failure to progress to alloHSCT. At 5 years, overall survival (OS) was 44% after sib alloHSCT, 36% after MUD alloHSCT, and 19% after chemotherapy. After adjustment for sex, age, and white blood count and excluding chemotherapy-treated patients who relapsed or died before the median time to alloHSCT, only relapse-free survival remained significantly superior in the alloHSCT group (odds ratio 0.31, 95% confidence interval 0.16-0.61). An intention-to-treat analysis, using the availability or not of a matched sibling donor, showed 5-year OS to be nonsignificantly better at 34% with a donor versus 25% with no donor. This prospective trial in adult Ph+ ALL indicates a modest but significant benefit to alloHSCT. This trial has been registered with clinicaltrials.gov under identifier NCT00002514 and as ISRCTN77346223.

scholarly journals P190BCR-ABL1 in a Patient with Philadelphia Chromosome Positive T-Cell Acute Lymphoblastic Leukemia: A Rare Case Report and Review of Literature

2021 ◽  
pp. 1040-1050
Author(s):  
Samah Kohla ◽  
Sarah EL Kourashy ◽  
Zafar Nawaz ◽  
Reda Youssef ◽  
Ahmad Al-Sabbagh ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Rare Case ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Cytogenetic Abnormality ◽  
Rare Case Report ◽  
Philadelphia Chromosome Positive

T-acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) is rare and aggressive leukemia. Philadelphia chromosome positive (Ph+) is the most common cytogenetic abnormality in chronic myeloid leukemia (CML) and B-acute lymphoblastic leukemia (B-ALL). Ph+ T-ALL is exceeding rare and has a therapeutic and prognostic significance. The incidence and outcome of Ph+ T-ALL are unknown. Differentiation between Ph+ T-ALL/LBL and T-cell lymphoblastic crises of CML may be difficult. We report a rare case of adult de novo T-ALL with significant monocytosis, having Ph+ with (P190 <i>BCR-ABL1</i>) as a cytogenetic abnormality. He was treated with ALL induction chemotherapy and imatinib and achieved complete remission, then relapsed twice and expired shortly after the last CNS relapse.

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