mycophenolic-acid and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive

Hematopoietic stem cell transplantation could improve the prognosis of malignant hematologic diseases. Peripheral blood stem cell transplantation (PBSCT) has been gradually used as an alternative to bone marrow transplantation (BMT). This study was to observe the efficacy of allogeneic PBSCT (allo-PBSCT) or autologous PBSCT (auto-PBSCT) on malignant hematologic diseases.. From Jul. 2003 to May 2006, 53 patients with malignant hematologic diseases underwent PBSCT in the First Affiliated Hospital of Zhengzhou University. PBSCs were mobilized with granulocyte colony-stimulating factor (G-CSF) or chemotherapy combined with G-CSF. Auto-PBSCT group received infusion of CD34+ cells at a median of 3.0x10(6) cells/kg; allo-PBSCT group received infusion of CD34+ cells at a median of 6.2x106 cells/kg. MAC regimen was used in auto-PBSCT group as conditioning regimen; amended BU/CY regimen was used in allo-PBSCT group. Methotrexate (MTX) combined with cyclosporine A (CsA) and MMF was used for graft-versus-host disease (GVHD) prophylaxis. Antilymphocyte globulin (ALG) was used in 1 patient with 1 mismatched locus in allo-PBSCT group.. The median time for neutrophils to reach 0.5x10(9)/L and platelets to reach 20x10(9)/L were 13 days and 19 days in auto-PBSCT group, 12 days and 15 days in allo-PBSCT group. In allo-PBSCT group, grade I-III acute GVHD occurred in 31.4% cases, and chronic GVHD developed in 71.4% cases. The relapse rate was 38.9% in auto-PBSCT group and 5.7% in allo-PBSCT group. The 700-day disease-free survival rate (DFS) was 57.9% in auto-PBSCT group, and 69.5% in allo-PBSCT group.. PBSCT can provide rapid hematopoietic reconstitution. It is a better choice for the cure of malignant hematologic diseases.

Topics: Adolescent; Adult; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Child; Cyclosporine; Disease-Free Survival; Female; Follow-Up Studies; Graft vs Host Disease; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Transplantation Conditioning; Transplantation, Homologous; Young Adult

Toxicities have limited the use of allogeneic hematopoietic cell transplantation (HCT) to younger, medically fit patients. In a canine HCT model, a combination of postgrafting mycophenolate mofetil (MMF) and cyclosporine (CSP) allowed stable allogeneic engraftment after minimally toxic conditioning with low-dose (200 cGy) total-body irradiation (TBI). These findings, together with the known antitumor effects of donor leukocyte infusions (DLIs), led to the design of this trial. Forty-five patients (median age 56 years) with hematologic malignancies, HLA-identical sibling donors, and relative contraindications to conventional HCT were treated. Immunosuppression involved TBI of 200 cGy before and CSP/MMF after HCT. DLIs were given after HCT for persistent malignancy, mixed chimerism, or both. Regimen toxicities and myelosuppression were mild, allowing 53% of eligible patients to have entirely outpatient transplantations. Nonfatal graft rejection occurred in 20% of patients. Grades II to III acute graft-versus-host disease (GVHD) occurred in 47% of patients with sustained engraftment. With median follow-up of 417 days, survival was 66.7%, nonrelapse mortality 6.7%, and relapse mortality 26.7%. Fifty-three percent of patients with sustained engraftment were in complete remission, including 8 with molecular remissions. This novel allografting approach, based on the use of postgrafting immunosuppression to control graft rejection and GVHD, has dramatically reduced the acute toxicities of allografting. HCT with the induction of potent graft-versus-tumor effects can be performed in previously ineligible patients, largely in an outpatient setting. Future protocol modifications should reduce rejection and GVHD, thereby facilitating studies of allogeneic immunotherapy for a variety of malignancies. (Blood. 2001;97:3390-3400)

Topics: Adult; Aged; Aging; Cause of Death; Cyclosporine; Female; Graft Rejection; Graft vs Tumor Effect; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing; Humans; Immunosuppressive Agents; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Middle Aged; Multiple Myeloma; Mycophenolic Acid; Neutrophils; Platelet Count; Remission Induction; Survival Rate; T-Lymphocytes; Transplantation Conditioning; Whole-Body Irradiation

To explore the therapeutic efficacy of allo-geneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelogenous leukemia (CML) patients with T315I mutation.. Retrospective analyses were conducted for 4 patients with T315I mutation of CML undergoing allo-HSCT from June 2012 to January 2014, including 2 cases in acceleration phase and 2 in chronic phase. There were 2 males and 2 females with ages from 26 to 45 years. Two patients received HLA-matched sibling allo-geneic peripheral blood stem cell transplantation (allo-PBSCT) while another 2 unrelated cord blood stem cell transplantation (UCBT). No splenomegaly was found before transplantation. One case had F317L mutation. All of them were treated with imatinib before transplantation. And the time from medication to T315I mutation was 20-35 months. All of them were conditioned with myeloablative regimen and received a combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) for preventing graft-versus-host disease (GVHD).. Myeloid implantation was achieved in all of them. The time of absolute neutrophil count (ANC) ≥ 0.5×10(9)/L were 10-28 days. One patient whose platelet was not implanted died from severe pulmonary infection at Day 88 post-transplantation. For 3 patients, platelet ≥ 20×10(9)/L were 15-33 days. But the marrow short tandem repeat (STR)-PCR was 100% donor type at the time of 30 days post-transplantation in all patients. One case of UCBT developed pre-implantation immune response syndrome (PES) and one acute GVHD of gradeI at Day 12 after allo-PBSCT. However both were controlled after treatment with methylprednisolone. And 1/3 evaluatable patients developed chronic GVHD. BCR/ABL transcript was detected by qualitative PCR after transplantation. And all BCR/ABL fusion genes turned negative after 30 days of transplantation. Up to the follow-up endpoint, there was no relapse except for one mortality. And the time of disease-free survival was 133, 248 and 704 days respectively.. Allo-HSCT is currently the optimal treatment for T315I mutation of CML. And umbilical cord blood is an ideal donor for those patients without HLA-matched sibling donor.

Topics: Adult; Allografts; Benzamides; Cord Blood Stem Cell Transplantation; Cyclosporine; Disease-Free Survival; Female; Fusion Proteins, bcr-abl; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Mutation; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Piperazines; Pyrimidines; Retrospective Studies; Siblings

To evaluat the efficacy and safety of myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with imatinib for advanced chronic myeloid leukemia (CML), 15 patients with accelerated phase (n=6) or blast crisis (n=9) were enrolled in this study. All the patients were conditioned with cyclophosphamide and busulfan, and treated with cyclosporin (CsA)/methotrexate (MTX)/mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. Eleven of these 15 patients (73.3%) achieved complete hematologic response to pre-transplant imatinib, and six (40%) achieved a cytogenetic response. No engraftment failure was observed and the early transplant-related mortality was only 6.7%. Grade 3/4 acute GVHD occurred in 13.3% of patients. Chronic GVHD was observed in 61.5%, including 23.1% suffered from extensive disease. The 5-year estimated rates of relapse, transplant-related mortality and overall survival were 21.0±10.8% 13.7±10.8% and 66.0±12.4%, respectively. Ten (66.7%) of 15 patients are alive with complete molecular remission, even after a median follow-up of 25 months after withdrawal of imatinib. In conclusion, even CML in advanced phases may have a satisfactory outcome after myeloablative allo-HSCT combined with imatinib, which may provide good remission prior to transplantation and reduce relapse risk, with low toxicity.

Topics: Adult; Benzamides; Blast Crisis; Busulfan; Combined Modality Therapy; Cyclophosphamide; Cyclosporine; Disease Progression; Female; Follow-Up Studies; Graft Survival; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Myeloablative Agonists; Piperazines; Pyrimidines; Remission Induction; Survival Rate; Transplantation Conditioning; Transplantation, Homologous

The incidence of certain malignancies is significantly higher after organ transplant. However, there are rare reports of chronic myeloid leukemia in the posttransplant setting. The average reported interval between a transplant and the diagnosis of chronic myeloid leukemia is 44 months (range, 10- 96 mo). We report 2 patients with chronic myeloid leukemia within 1 year of a kidney transplant, which is significantly shorter than those previously reported. Both patients were receiving mycophenolate mofetil and tacrolimus for immunosuppression. They were treated with imatinib for chronic myeloid leukemia, and both patients demonstrated an isolated elevation of serum alkaline phosphatase that was directly correlated with imatinib. Despite a potential interaction between the 2 drugs, blood levels of tacrolimus and imatinib were not elevated during the course of treatment. Isolated elevation of alkaline phosphatase in this particular setting has not been reported previously.

Topics: Adolescent; Alkaline Phosphatase; Antineoplastic Agents; Benzamides; Biomarkers; Drug Therapy, Combination; Humans; Imatinib Mesylate; Immunosuppressive Agents; Kidney Transplantation; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Mycophenolic Acid; Piperazines; Pyrimidines; Tacrolimus; Time Factors; Up-Regulation

We describe herein the clinical courses and outcomes of 26 patients who received oral mycophenolate mofetil (MMF) for the treatment of steroid-resistant refractory or steroid-dependent acute or chronic graft-versus-host disease (GVHD) in a single institution. In most cases, 1,500 mg/day of MMF is a median dose (range 500-3,000 mg/day) and administered for 116.5 days (range 9-584 days) along with calcineurin inhibitors and steroids. Although 20 patients (77%) showed rapid improvement of GVHD symptoms, of 15 patients, 13 (87%) showed acute GVHD; of 11 patients, 7 (64%) showed chronic GVHD; most patients (54%) experienced infection during MMF administration, including 5 cases with life-threatening infection. Positive cytomegalovirus (CMV) antigenemia was also observed in 19 patients (73%), but no patients developed CMV infection. Within the median follow-up of 12.5 months (range 0.5-67 months), 10 patients (39%) died. This small study demonstrates that MMF offers an alternative tool for rescuing steroid-refractory or steroid-dependent GVHD, but increases the risk of developing life-threatening infection.

Topics: Acute Disease; Adult; Anemia, Aplastic; Chronic Disease; Female; Graft vs Host Disease; Humans; Immunocompromised Host; Immunosuppressive Agents; Infections; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Male; Middle Aged; Mycophenolic Acid; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Risk Factors; Stem Cell Transplantation; Survival Analysis; Transplantation, Homologous; Young Adult

Kinetics of BCR-ABL transcript elimination and its prognostic implications on relapse were analyzed in patients with chronic myeloid leukemia (CML) after reduced intensity hematopoietic cell transplantation (HCT). In all, 19 CML patients were conditioned with 2 Gy total-body irradiation in combination with (n=14) or without (n=3) fludarabine 3 x 30 mg/m(2) (Flu) or 4.5 Gy total lymphoid irradiation (TLI) with Flu and OKT3 3 x 5 mg (n=2) and were treated with cyclosporine (CSP) and mycophenolate mofetil after allogeneic HCT. BCR-ABL transcripts were analyzed by nested RT-PCR and Taqman((R)) RT-PCR on days +28, +56 and +84 after HCT and were evaluated for their association with relapse. Of the 19 patients, 14 achieved sustained remissions of which six had a negative RT-PCR 28 days after HCT. Five patients relapsed +41, +54, +57, +136 and +234 days after HCT. Predictors for relapse were advanced disease stage (P=0.02) and slow reduction of BCR-ABL transcripts at day 28 (P=0.006) and day 56 (P=0.047) post-transplant. We conclude that a complete clearance of BCR-ABL transcripts is achievable within 4 weeks from HCT even after minimal conditioning and that early kinetics of BCR-ABL transcripts significantly correlate with the probability of hematological relapse.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclosporine; Female; Fusion Proteins, bcr-abl; Hematopoietic Stem Cell Transplantation; Hematopoietic System; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Mycophenolic Acid; Neoplasm Recurrence, Local; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Sensitivity and Specificity; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Whole-Body Irradiation

To explore the feasibility of HLA mismatched hemopietic stem cell transplants for the treatment of leukemia.. Between July 2000 and December 2001, seven patients received hemopietic stem cell transplants(HSCT) with HLA mismatched family donors, including 3 chronic myelocytic leukemia (CML), 3 acute nonlymphocytic leukemia (ANLL), and 1 acute lymphocytic leukemia (ALL). Stem cell sources were bone marrow(n = 1) or G-CSF mobilized peripheral blood (n = 6). All the patients were conditioned with busulfan (BU) 12 mg.kg-1 and cyclophosphamide (CY) 3.6 g.m-2, of whom 4 were conditioned with additioned antithymocyte globulin(ATG). Graft versus host disease (GVHD) prophylaxis regimen consisted of cyclosporin-A (CSA), methotrexate (MTX) and mycophenolate mofetil(MMF).. One patients received 3.41 x 10(8) kg-1 mononuclear cells(MNC) from bone marrow; six patients received a mean number of 8.46 x 10(8) kg-1 (4.3 x 10(8)-15.4 x 10(8) kg-1) MNC from peripheral blood. The mean time of ANC > 0.5 x 10(9) L-1 was day 13 (11-16), and BPC > 20.0 x 10(9) L-1 was day 16 (11-23). All the patients got engraftment successfully and attained CR. Acute I-II GVHD occurred in 3(42.9%) patients, no acute III-IV GVHD occurred and extensive chronic GVHD did in 2(28.6%) patients. All the patients were alive and well after 6-24 months' follow-up.. (1) BU/CY plus ATG appears to be an effective conditioning regimen for HLA mismatched allogenic stem cell transplants. (2) G-CSF mobilized peripheral blood stem cells may be the source of stem cells even for HLA mismatched hemopietic stem cell transplants.

Topics: Bone Marrow Transplantation; Cyclophosphamide; Cyclosporine; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Histocompatibility Antigens Class II; HLA Antigens; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Methotrexate; Mycophenolic Acid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Homologous

To evaluate the efficacy of combination of mycophenolate mofetil (MMF) with cyclosporine (CsA) and methotrexate (MTX) on prophylaxes of acute graft-versus-host disease (GVHD) in HLA-matched allogeneic peripheral blood stem cell transplantation (allo-PBSCT).. Thirty-nine patients with acute leukemia (n = 21) and chronic myeloid leukemia (n = 17) and severe aplastic anemia (n = 1) were treated with allo-PBSCT from HLA matched siblings (n = 36) or unrelated donors (n = 3). Twenty-six patients were in CsA + MTX group. CsA was given at a dosage of 2 mg.kg(-1).d(-1) by continuous intravenous injection for 24 h, since on day(-1) and injection of CsA was changed to oral administration of CsA around day 18. CsA was tapered by 10% per week after day + 90. MTX was given at the dosage of 15 mg at day + 1, and 10 mg at day + 3, + 6 and + 11, respectively. Thirteen patients were included in MMF + CsA + MTX group with the same dosage of CsA and MTX as above but omitted at day + 11. MMF of 2 g/day was added orally from day + 1 to day + 28 post transplantation.. All patients in both groups were successfully engrafted. The days of recovery of neutrophils and platelets were not significantly different between two groups (P > 0.05). The incidence of acute GVHD in MMF + CsA + MTX group (7.6%) was significantly lower than that in CsA/MTX group (46.2%, P < 0.05). Incidence of grade II approximately IV GVHD in MMF group was 0 while that in control group was 23.0%. The incidence of severe mucositis was lower in MMF group (15.4%) than in the control group (30.8%) (P < 0.05).. The regimen of MMF + CsA + MTX for prevention of acute GVHD in allo-PBSCT is more efficient than that of CsA + MTX, without adversely affecting the engraftment and relapse rate.

Topics: Acute Disease; Adult; Anemia, Aplastic; Blood Platelets; Chronic Disease; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Incidence; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Male; Methotrexate; Middle Aged; Mouth Mucosa; Mycophenolic Acid; Neutrophils; Transplantation, Homologous; Treatment Outcome