scholarly journals Chronic Myeloid Leukemia Relapsing 25 Years after Allogenic Stem Cell Transplantation

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Håkon Reikvam ◽  
Jørn Skavland ◽  
Stein-Erik Gullaksen ◽  
Randi Hovland ◽  
Tobias Gedde-Dahl ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Allogenic Stem Cell Transplantation ◽  
Relapsed Disease

Chronic myeloid leukemia (CML) is a myeloproliferative disorder in which neoplastic cells exhibit the Philadelphia chromosome and the related oncoproteinBCR-ABL1. Allogeneic stem cell transplantation (allo-SCT) was considered the first-line treatment for CML, before the introduction of tyrosine kinase inhibitors (TKIs). However, patients are at risk for relapse years after transplantation. We present a patient who relapsed 25 years after allo-SCT for chronic phase CML. Polymerase chain reaction (PCR) detected gradually evaluated levels ofBCR-ABL1transcripts, eventually leading to the diagnosis of relapsed disease. Additional mutational analyses did not reveal mutations in theBCR-ABL1gene, or other cooperating mutations. The patient was successfully treated with imatinib 400 mg daily, leading to new molecular remission. The case presentation emphasizes the need for long-term follow-up of such patients and the potential benefit of initiating TKI treatment with early signs of relapse.

Three decades of transplantation for chronic myeloid leukemia: what have we learned?

Blood ◽  
2011 ◽  
Vol 117 (3) ◽  
pp. 755-763 ◽  
Author(s):  
Jiří Pavlů ◽  
Richard M. Szydlo ◽  
John M. Goldman ◽  
Jane F. Apperley
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Hematopoietic Stem

Abstract Last year marked 30 years of hematopoietic stem cell transplantation as a curative treatment of chronic myeloid leukemia (CML). Initially studies used stem cells from identical twins but techniques rapidly developed to use cells first from HLA-identical siblings and later unrelated donors. During the 1990s CML became the most frequent indication for allogeneic transplantation worldwide. This, together with the relative biologic homogeneity of CML in chronic phase, its responsiveness to graft-versus-leukemia effect and the ability to monitor low level residual disease placed CML at the forefront of research into different strategies of stem cell transplantation. The introduction of BCR-ABL1 tyrosine kinase inhibitors during the last decade resulted in long-term disease control in the majority of patients with CML. In those who fail to respond and/or develop intolerance to these agents, transplantation remains an effective therapeutic solution. The combination of tyrosine kinase inhibitors with transplantation is an exciting new strategy and it provides inspiration for similar approaches in other malignancies.

scholarly journals Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias

Blood ◽  
2011 ◽  
Vol 118 (20) ◽  
pp. 5697-5700 ◽  
Author(s):  
Franck Emmanuel Nicolini ◽  
Grzegorz W. Basak ◽  
Simona Soverini ◽  
Giovanni Martinelli ◽  
Michael J. Mauro ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Philadelphia Chromosome ◽  
Blast Phase

Abstract T315I+ Philadelphia chromosome–positive leukemias are inherently resistant to all licensed tyrosine kinase inhibitors, and therapeutic options remain limited. We report the outcome of allogeneic stem cell transplantation in 64 patients with documented BCR-ABLT315I mutations. Median follow-up was 52 months from mutation detection and 26 months from transplantation. At transplantation, 51.5% of patients with chronic myeloid leukemia were in the chronic phase and 4.5% were in advanced phases. Median overall survival after transplantation was 10.3 months (range 5.7 months to not reached [ie, still alive]) for those with chronic myeloid leukemia in the blast phase and 7.4 months (range 1.4 months to not reached [ie, still alive]) for those with Philadelphia chromosome–positive acute lymphoblastic leukemia but has not yet been reached for those in the chronic and accelerated phases of chronic myeloid leukemia. The occurrence of chronic GVHD had a positive impact on overall survival (P = .047). Transplant-related mortality rates were low. Multivariate analysis identified only blast phase at transplantation (hazard ratio 3.68, P = .0011) and unrelated stem cell donor (hazard ratio 2.98, P = .011) as unfavorable factors. We conclude that allogeneic stem cell transplantation represents a valuable therapeutic tool for eligible patients with BCR-ABLT315I mutation, a tool that may or may not be replaced by third-generation tyrosine kinase inhibitors.

Stem cell transplantation for chronic myeloid leukemia in children

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1224-1231 ◽  
Author(s):  
Kate Cwynarski ◽  
Irene A. G. Roberts ◽  
Simona Iacobelli ◽  
Anja van Biezen ◽  
Ronald Brand ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Disease Stage ◽  
Hematopoietic Stem ◽  
Advanced Phase

Abstract Hematopoietic stem cell transplantation (SCT) is the only proven cure for chronic myeloid leukemia (CML), a rare disease in childhood. We report outcomes of 314 children with Philadelphia-chromosome–positive (Ph+) CML undergoing SCT from HLA-matched siblings (n = 182) or volunteer-unrelated donors (VUD; n = 132). Three-year overall survival (OS) and leukemia-free survival (LFS) rates were 66% and 55% (n = 314). For 156 children in first chronic phase (CP1) who underwent transplantation from HLA-identical siblings, OS and LFS rates were 75% and 63%. For 97 children who underwent SCT in CP1 from VUD, 3-year OS and LFS rates were 65% and 56%, reflecting higher transplantation-related mortality (TRM) after VUD SCT (35% vs 20%; multivariate hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.0-3.5; P = .05). In a multivariate model for OS and LFS, outcomes were superior in CP1 than in advanced phase (AP/CP1) (OS HR, 2.0; 95% CI, 1.3-3; P = .001; LFS HR, 1.8; 95% CI, 1.2-2.6; P = .003). For relapse, donor source (VUD/sibling) (HR, 0.38; 95% CI, 0.19-0.76; P = .006) and disease stage (AP/CP1) (HR, 2.4; 95% CI, 1.36-4.3; P = .003) were significant. This is the first large series to show that SCT confers long-term LFS in most children with CML and helps assess alternative therapy, including tyrosine kinase inhibitors.

Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase

Blood ◽  
2003 ◽  
Vol 101 (2) ◽  
pp. 441-445 ◽  
Author(s):  
Reuven Or ◽  
Michael Y. Shapira ◽  
Igor Resnick ◽  
Avraham Amar ◽  
Aliza Ackerstein ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Chronic Phase ◽  
Mixed Chimerism ◽  
High Dose ◽  
Disease Free

Reduced-intensity or nonmyeloablative stem cell transplantation (NST) is designed to induce host-versus-graft tolerance by engraftment of donor stem cells. The rationale behind NST is to induce optimal graft-versus-leukemia (GVL) effects for elimination of all malignant cells by donor alloreactive immunocompetent cells as an alternative to standard high-dose myeloablative chemoradiotherapy. NST based on the use of fludarabine, low-dose busulfan, and anti–T-lymphocyte globulin (ATG) was employed in 24 patients aged 3 to 63 years with chronic myeloid leukemia (CML) in first chronic phase (CP). Graft-versus-host disease (GVHD) prophylaxis consisted of low-dose cyclosporine (CSP), in some cases with low-dose methotrexate. Early discontinuation of CSP was attempted in cases of mixed chimerism in an attempt to amplify GVL effects. All 24 patients showed rapid 3-lineage engraftment, mostly without complete aplasia; 6 patients did not require transfusion of any blood products. NST was associated with minimal procedure-related toxicity. The incidence of acute GVHD (grade I or higher) was 54%; however, this incidence increased following CSP withdrawal. After a follow-up of up to 70 months (median, 42 months), 21 of 24 patients remained alive and disease free. The GVL effects induced by donor immunocompetent lymphocytes eradicated all host hematopoietic cells, as evidenced by molecular testing. The Kaplan-Meier probability of survival and disease-free survival at 5 years is 85% ± 8% (95% confidence interval, 70%-100%). NST may successfully replace myeloablative stem cell transplantation, providing a safer, well-tolerated therapeutic option for all patients with CML in first CP with a matched donor. However, this conclusion must be tested in a prospective randomized clinical trial.

HLA-Haploidentical Related Hematopoietic Stem Cell Transplantation and Mesenchymal Stem Cell Transplantation in Patients with Hematologic Malignancies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5408-5408
Author(s):  
Xiaoyan Zhang ◽  
Jianyong Li ◽  
Kejiang Cao ◽  
Hanxin Wu ◽  
Hua Lu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Clinical Features ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Hematologic Malignancies ◽  
Hematopoietic Stem

Abstract Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only way to cure many hematologic malignancies. HLA-haploidentical related HSCT was performed in case of lack of HLA-matched donors. From the results of in-vitro and animal studies, Mesenchymal stem cells (MSCs) transplanted simultaneously with hematopoietic stem cells (HSCs) may support hematopoietic regeneration and have the immunomodulatory effect. MSCs together with HSCs transplantation from the same HLA-haploidentical donor were used in patients with hematologic malignancies. Patients and Methods: Three patients were chronic myeloid leukemia (blast crisis), chronic myeloid leukemia (chronic phase) and refractory T-cell lymphoblastic lymphoma (leukemia phase) respectively. Complete demographic and clinical details of these 3 patients are shown in Table 1. Bone marrow mononuclear cells obtained from their HLA-haploidentical related donors were cultured and expanded in vitro about 2 months before transplantation. Immunophenotype of the harvested cells were detected in order to identify them. After conditioned by cytosine arabinoside/cyclophosphamide/total body irradiation regimen, patients were co-transplanted with HSCs and ex-vivo expanded MSCs. Cyclosporine, methotrexate, antithymocyte globulin, mycophenolate mofetil and anti-CD25 monoclonal antibody were used together for prophylaxis of GVHD. Clinical features after transplantation in these patients were observed. Results: About 2×106 MSCs per kilogram of recipients’ weight were successfully expanded from bone marrow samples. These cells were CD73, CD90, CD105 positive and CD34, CD45, CD38, CD10, CD20, CD33, HLA-DR negative by flow cytometric analysis. No adverse response was observed during and after infusion of MSCs. Hematopoietic reconstruction was successful in all the patients. And they had full donor-type chimerism 1 month after transplantation. N1 received donor lymphocyte infusion (DLI) to prevent the relapse. N2 relapsed and received the therapy of STI571 combined with DLI. She had a complete remission at last. No graft-versus-host disease (GVHD) was observed in N1 and N2 until they received DLI. N1 died of infection 11 months after transplantation. N2 and N3 now have been followed up for 41 and 31 months respectively. Clinical features of patients after transplantation are shown in Table 2. Conclusions: Bone marrow derived MSCs can be tolerant well in HLA-haploidentical HSCT. Its exact effect in human HLA-haploidentical allogeneic HSCT needs to be studied further. Tab.1 Patient Demographic and Clinical Data Patient Diagnosis Age Sex Course of disease before transplantation Donor Mismatched HLA loci Abbr: LPL - lymphoblastic lymphoma; CML - chronic myeloid leukemia; BC - blast crisis; CP - chronic phase; yr - year; mo - month N1 T-LPL 22 F 7 yr mother 3 N2 CML-BC 32 F 6mo sibling brother 3 N3 CML-CP 22 M 5mo father 3 Tab.2 Clinical features of patients after transplantation Patient Hematopoietic reconstruction Donor-type chimerism Time of relapse time of DLI acute GVHD chronic GVHD survival Abbr: DLI - donor lymphocyte infusion; d - day; mo - month N1 15 d 100% no 5 mo IV (after DLI) extensive die in 11 mo N2 16 d 100% 6mo 6 mo IV (after DLI) no >41 mo N3 15 d 100% no no I limited >31 mo

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.

Imatinib mesylate experience of young patients with chronic myeloid leukemia in chronic phase—Care to cure

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7072-7072
Author(s):  
D. Biswajit ◽  
R. Rejiv ◽  
N. Manjunath ◽  
G. Prasad ◽  
S. Lakshmi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Adverse Effects ◽  
Stem Cell Transplantation ◽  
Imatinib Mesylate ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Young Patients ◽  
Chronic Phase ◽  
Molecular Response

7072 Background: Chronic myeloid leukemia (CML) with introduction of imatinib has been transformed into a chronic illness. The options of treatment in a patient less than 35 years include imatinib or allogenic stem cell transplantation. Hence we studied this unique subset to look at the response rates, adverse effects, progression free survival, and overall survival with imatinib mesylate. Methods: 477 patients with Philadelphia positive CML in chronic phase were retrospectively analyzed from January 2002 to December 2007 at Cancer Institute (WIA), Chennai, India. Standard criteria were used for response evaluation and adverse effects. Results: A total of 248 young CML patients with age less than 35 years (51.9%) were diagnosed in chronic phase. The median age of study population was 27 years (4–35). The male to female ratio was 1.9: 1. Risk stratification was done using Sokal index and were classified into low (32.3%), intermediate (50.4%), and high (17.3%). All patients received imatinib 400 mg as the initial dose. Complete hematological remission (CHR) was seen in 96.7%.Cytogenetic (FISH) and molecular (RTPCR) monitoring was possible in 53.2% and 17.3%, respectively. 72% of the patients had major cytogenetic response. Major molecular response was seen in 34.8% while complete molecular response occurred in 23.2% of the patients. Primary and secondary imatinib failure was seen in 3.1% and 16.9%, respectively. 6.7% had grade 3 and grade 4 hematological toxicities. The other common non hematological toxicities included pedal edema (13.7%), hypo or hyper pigmentation (60.0%), hyalgia (14.5%), diarrhea (1.6%), and liver dysfunction (1.6%). None of the patients discontinued imatinib due to toxicities. The 3-year DFS and OS was 86.2% and 89.5%, respectively. Patients with male sex (p = 0.04), spleen > 8 cm (p = 0.02), high sokal index (p = 0.02), and loss of CHR (p < 0.001) were associated with poor outcome. Conclusions: Imatinib in young patients have an excellent tolerance and response. A small subset does not respond to therapy or develop resistance during treatment. Hence it is essential to identify these poor responders and to offer stem cell transplantation at the earliest. No significant financial relationships to disclose.

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.

Sign in / Sign up

Export Citation Format

Share Document