Long-Term Outcome of Nonmyeloablative Allogeneic Stem Cell Transplantation in First Chronic Phase of Chronic Myeloid Leukemia

2006 ◽  
Vol 1 (2) ◽  
pp. 123-129
Author(s):  
Benjamin Gesundheit ◽  
Shimon Slavin ◽  
Michael Y. Shapira ◽  
Menachem Bitan ◽  
Avraham Amar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Term Outcome ◽  
Long Term Outcome

scholarly journals Durability of responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia

Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2712-2716 ◽  
Author(s):  
Francesco Dazzi ◽  
Richard M. Szydlo ◽  
Nicholas C. P. Cross ◽  
Charles Craddock ◽  
Jaspal Kaeda ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Molecular Remission ◽  
Donor Lymphocyte Infusions ◽  
Median Interval

Abstract An analysis was performed of the response to treatment with donor lymphocyte infusions (DLI) and the survival in 66 consecutive patients who relapsed after primary treatment by allogeneic stem cell transplantation for BCR-ABL–positive chronic myeloid leukemia. The transplant donor was an HLA-identical sibling (n = 35) or a “matched” unrelated volunteer (n = 31). Fifty-seven patients were transplanted in chronic phase, eight in accelerated phase, and one in second chronic phase. The recognition of relapse was based on precise molecular, cytogenetic, or hematologic criteria. The median interval from transplant to relapse was 12 months (range 3-85). The median interval from relapse to initiation of DLI was 9.4 months (range 1-70). Patients received DLI from their original transplant donors on a bulk-dose (n = 34) or on an escalating-dose (n = 32) regimen. Patients were monitored serially by hematologic, cytogenetic, and molecular criteria. Molecular remission was defined by the finding of negative results by nested primer reverse transcriptase polymerase chain reaction (RT-PCR) for BCR-ABL transcripts on two consecutive occasions, subject to satisfactory controls. Forty-four patients (67%) achieved molecular remission. Patients who had relapsed to advanced phase disease and patients with short intervals between transplant and relapse had significantly lower probabilities of achieving molecular remission. Of the 44 patients who achieved molecular remission, 4 reverted to a PCR-positive status at 15, 18, 37, and 87 weeks after remission. The probability of survival for patients who achieved molecular remission was significantly better than for those who failed to do so (95% versus 53% at 3 years post-DLI,P = .0001). We conclude that the majority of molecular remissions after DLI are durable, and thus the majority of responding patients may prove to have been cured.

A Fludarabine-Based Non-Myeloablative Conditioning Regimen in Allogeneic Stem Cell Transplantation from Related and Unrelated Donors in Chronic Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5372-5372
Author(s):  
Yi Luo ◽  
He Huang ◽  
Zhen Cai ◽  
Yamin Tan ◽  
Xiaoyan Han
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Conditioning Regimen ◽  
Chronic Phase ◽  
Myeloablative Conditioning ◽  
Unrelated Donors

Abstract Objective: To evaluate the efficacy and safety of a fludarabine-based non-myeloablative conditioning regimen in allogeneic stem cell transplantation (SCT)from related and unrelated donor for chronic myeloid leukemia in chronic phase(CML-CP). Methods: Fifteen consecutive patients with CML-CP between May, 2005 and July, 2006 were treated with a single non-myeloablative conditioning regimen in this study. They were 10 males and 5 females with a median age of 41 years (range, 18–49). Donors were HLA-A, B and high resolution DR fully matched siblings (n=8), matched unrelated donors (n=6), and 1-locus mismatched unrelated donors (n=1). The stem cells were collected from either peripheral blood (n=9) or bone marrow (n=6). The conditioning regimen included fludarabine 30 mg/m2/day (days -10 to -5), oral busulfan 4 mg/kg/day (n=4 patients), or intravenous busulfan 3.2 mg/kg/day (n=11 patients) (days -6 to -5) and anti-thymocyte globulin (Fresenius, Germany) (5mg/kg/day) (days -4 to-1). Mycophenolate mofetil combined with cyclosporin A and methotrexate was used for prevention of acute graft-versus-host disease(GVHD) after transplantation. Lipoprostagandin E1 was used in prophylactic regimen for hepatic veno-occlusive disease(VOD). To assess engraftment, degree of chimerism, minimal residual disease and relapse, all patients were monitored by cytogenetic analysis and donor vs host-specific DNA markers using short tandem repeats (STR) assay. The average cell number of MNC transfused was 4.83 (3.14~11.5)×108/kg; CD34+ cells were 3.47(2.38~6.24)×106/kg, CFU-GM was 2.15 (1.85~3.06) ×105/kg. Results: Engraftment of neutrophils and platelets was achieved in 14 out of 15 (93.3%) patients within a median of 13 days (range, 8–21) and 18 days (range, 10–35), respectively. Fourteen patients achieved complete donor chimerism in the peripheral blood before day +35 and one developed graft failure. No patients developed acute GVHD and VOD, but one died from interstitial pneumonia while she was in continuous complete remission 2 months following transplantation. With a median follow-up of 5 months (range 1.5 to 15), 13 of them were still in CCR. The overall non-relapse mortality in this group was 6.67% (1/15 patients). Overall survival, and disease-free survival rates were 93.3% and 86.7%, respectively. Conclusion: A fludarabine-based non-myeloablative conditioning regimen in allogeneic stem cell transplantation from related and unrelated donors is an effective and safe choice for patients with chronic myeloid leukemia in chronic phase.

Imatinib mesylate (STI571) in the treatment of relapse of chronic myeloid leukemia after allogeneic stem cell transplantation

Blood ◽  
2002 ◽  
Vol 99 (10) ◽  
pp. 3861-3862 ◽  
Author(s):  
Eduardo Olavarria ◽  
Charles Craddock ◽  
Francesco Dazzi ◽  
David Marin ◽  
Sarah Marktel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Imatinib Mesylate ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Specific Inhibitor ◽  
Chronic Phase ◽  
Donor Lymphocyte Infusion

Donor lymphocyte infusion (DLI) can restore durable molecular remission in a high percentage of patients with chronic myeloid leukemia (CML) who have relapses after allogeneic stem cell transplantation, but for patients who do not respond survival is poor. Imatinib mesylate (STI571) is a specific inhibitor of BCR-ABL tyrosine kinase that can induce hematologic and cytogenetic remissions in patients with CML. We report here a male patient who had a relapse to chronic phase after stem cell transplantation for CML, did not benefit from treatment with DLI, and then was administered STI571 at a dose of 400 mg daily. There was a rapid, complete hematologic response, and complete restoration of donor-type hematopoiesis (100% 46, XX marrow metaphases) was achieved after 6 months of therapy, though RT-PCR studies still detected BCR-ABL transcripts in the blood at low level. This case demonstrates that imatinib mesylate can be highly effective in the management of patients who have relapses after allograft for CML.

scholarly journals Long-Term Outcome of Myeloablative Allogeneic Stem Cell Transplantation for Multiple Myeloma

2007 ◽  
Vol 13 (8) ◽  
pp. 925-931 ◽  
Author(s):  
John Kuruvilla ◽  
John D. Shepherd ◽  
Heather J. Sutherland ◽  
Thomas J. Nevill ◽  
Janet Nitta ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Term Outcome ◽  
Long Term Outcome

scholarly journals High PR3 or ELA2 expression by CD34+ cells in advanced-phase chronic myeloid leukemia is associated with improved outcome following allogeneic stem cell transplantation and may improve PR1 peptide–driven graft-versus-leukemia effects

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 770-775 ◽  
Author(s):  
Agnes S. M. Yong ◽  
Katayoun Rezvani ◽  
Bipin N. Savani ◽  
Rhoda Eniafe ◽  
Stephan Mielke ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Cytotoxic T Lymphocyte ◽  
Chronic Phase ◽  
Advanced Phase ◽  
Ctl Responses

Abstract The primary granule proteins elastase (ELA2) and proteinase 3 (PR3) both contain the nonapeptide PR1, which can induce cytotoxic T lymphocyte (CTL) responses against chronic myeloid leukemia (CML) cells. To investigate whether eradication of CML after allogeneic stem cell transplantation (SCT) was influenced by PR3 and ELA2 gene expression or PR1-specific CTL responses, we studied cells from 87 CML patients and 27 HLA-A*0201+ donors collected prior to T-cell–depleted HLA-identical sibling SCT. For patients in advanced phase (AdP), a higher expression of both PR3 and ELA2 in CD34+ progenitors before SCT was associated with a lower incidence of relapse-related death, improved leukemia-free survival (LFS), and overall survival (OS); in chronic phase patients, no differences were observed. PR1-CTL responses were detected in 7 of 27 HLA-identical sibling donors, and associated with improved LFS and OS after SCT on follow-up. PR1-CTL responses detected in 7 of 28 CML patients before transplantation were not predictive of outcome and correlated inversely with PR3 and ELA2 expression. These findings suggest that assessment of PR3 and ELA2 expression in leukemic progenitors is useful for predicting posttransplantation outcome in AdP patients undergoing SCT. The presence of a donor immune response against PR1 may be advantageous and could be exploited therapeutically.

Chronic myeloid leukemia: current treatment options

Blood ◽  
2001 ◽  
Vol 98 (7) ◽  
pp. 2039-2042 ◽  
Author(s):  
John M. Goldman ◽  
Brian J. Druker
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Single Agent ◽  
Chronic Phase ◽  
High Rate ◽  
Interferon Α

The choice of primary treatment for patients with chronic myeloid leukemia (CML) diagnosed in chronic phase has become exceedingly difficult. There is little doubt that allogeneic stem cell transplantation can eradicate the leukemia and that a graft-versus-leukemia effect makes a major contribution to this result; conversely, only a minority of patients are eligible for transplantation, which still carries an appreciable risk for death or protracted illness. For most patients, interferon-α (IFN-α) prolongs life to some degree in comparison with hydroxyurea, but it is associated with considerable toxicity. The newly introduced tyrosine kinase inhibitor STI571 induces complete hematologic remission in almost all patients and is associated with a very high rate of cytogenetic response; its capacity to prolong life in comparison with IFN-α is not yet established. Here are reviewed some factors that predict survival after nontransplantation therapy and after allografting for CML in chronic phase. Two contrasting options are considered for managing the patient with newly diagnosed disease, and it can be concluded that, for now, allogeneic stem cell transplantation soon after diagnosis should continue to be offered as an option for selected patients. Further experience with the use of STI571 as a single agent or in combination with other antileukemic agents may alter the picture in the near future.

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