Influential Factors for the Collection of Peripheral Blood Stem Cells and Engraftment in Acute Myeloid Leukemia Patients in First Complete Remission

Although several studies have investigated factors influencing peripheral blood stem cell (PBSC) mobilization in patients with nonmyeloid malignancies in an effort to increase the efficiency of autologous PBSC transplantation (APBSCT), there are very few reports on the efficiency of PBSC mobilization in patients with leukemia. We analyzed the effects of influential variables on successful mobilization and the correlation between infused cell doses and engraftment in acute myeloid leukemia (AML) patients in first complete remission (CR1) who received APBSCT. Between May 1998 and May 2003, 34 patients with AML underwent APBSC collections at our institution. All patients were in CR1 at the time of transplantation. Except for 1 patient, all patients successfully achieved the target CD34(+) cell yield of > or = 2 x 10(6)/kg. Among progenitor cells, the CD34(+) cell dose and the colony-forming unit-granulocyte-macrophage count showed significant correlations with neutrophil and platelet engraftments. The time to neutrophil engraftment was inversely correlated to the number of infused CD34(+) cells (r = -0.67; P < .001), whereas the time to neutrophil engraftment was not significantly correlated with the number of monocytes (r = 0.20; P = .701) or the number of nucleated cells (r = 0.35; P = .062). The time to platelet engraftment was significantly correlated with the dose of infused CD34(+) cells (r = -0.47; P = .012). The univariate analysis showed that more CD34(+) cells per kilogram and more CD34(+) cells per kilogram per day were collected from patients who had a shorter interval (less than 2 months) between diagnosis and PBSC harvest (P = .0111). In conclusion, this study showed that the CD34(+) cell dose was most strongly correlated with a successful engraftment in AML CR1 patients who underwent APBSCT. The proper timing of PBSC collections should be explored to optimize the outcome of APBSCT in AML CR1 patients.     

自体造血干细胞移植治疗急性白血病

报告４例自体造血干细胞移植治疗急性非淋巴细胞性白血病。其中３例接受自体在干细胞移植，１例接受自体骨髓移植。４例均在初次完全缓解后经ＭＡＣ方法预处理，４例患者一均获得造血重建，已分别持续完全缓解４５９ｄ，３４２ｄ，３０５ｄ，１１２ｄ。     

自体骨髓移植结合强烈化疗治疗急性白血病疗效观察

为探讨减少自体骨髓移植（ABMT）后复发率和延长无病生存期。作者采用ABMT结合强烈化疗的方法治疗急性白血病。能列入统计的12例患者中,8例移植后已持续完全缓解19～79个月,中位数58.5个月。证明采用ABMT结合强烈化疗方法,可以减少急性白血病的复发率和延长无病生存期。     

Autologous Peripheral Blood Stem Cell Transplantation for Severe Multiple Sclerosis

We describe the results of a clinical trial to evaluate the feasibility and toxicity of autologous hematopoietic stem cell transplantation (auto-HSCT) for patients with progressive multiple sclerosis (MS). Fifteen patients (all patients with secondary progressive MS) were enrolled. The median expanded disability status scale (EDSS) score at baseline was 6.0 (range, 4.5-7.5). Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony-stimulating factor. In 9 patients, CD34+ cell selection was performed with a CliniMACS cell selection system, and 6 patients accepted infusion of unmodified peripheral blood stem cells. The modified BEAM (carmustine, teniposide, cytarabine, and melphalan) was the sole conditioning regimen used. The adverse effects included infections, mucositis, transient hepatotoxicity, and diarrhea. Three patients had flares of neurologic deterioration during mobilization, 8 patients had the same manifestation during transplantation, and 2 patients had similar flares within 3 months of transplantation. Six patients experienced continuous neurologic improvement after transplantation, 5 patients experienced neurologic progression, and 4 patients had stabilization of their disease. The confirmed progression-free rate was 63.8% at 49 months. The results of lymphocyte purging were no better than for no purging. Auto-HSCT proved to be safe and beneficial for some MS patients. Further studies are needed to establish the merit of this procedure for MS patients.     

Impact of Cytogenetics on Outcome of Stem Cell Transplantation for Acute Myeloid Leukemia in First Remission: A Large-Scale Retrospective Analysis of Data from the Japan Society for Hematopoietic Cell Transplantation

On the basis of transplantation data from the Japan Society for Hematopoietic Cell Transplantation, we retrospectively analyzed the impact of cytogenetics at diagnosis on the outcome of transplantation in 628 patients with acute myeloid leukemia who underwent autologous (n = 200), allogeneic related (n = 363), or allogenic unrelated (n = 65) stem cell transplantation (SCT) at first complete remission. For autologous SCT, patients at good cytogenetic risk had a significantly lower relapse rate (P = .017) and a significantly higher event-free survival (EFS) (P = .013) compared with those at intermediate risk. For allogeneic SCT, patients at good cytogenetic risk had a significantly lower relapse rate (P = .019) and insignificantly higher EFS (P = .093) than those at poor risk. For unrelated SCT, there was no significant difference in relapse rate or EFS between patients at good risk and those at intermediate risk. Comparison of the 3 transplantation modalities revealed that autologous SCT patients had a significantly higher incidence of relapse compared with related or unrelated SCT patients in the intermediate-risk group but not in the good-risk group. However, there were no significant differences in EFS among the 3 transplant modalities in either of these 2 risk groups. In multivariate analysis, cytogenetics was found to be an independent predictor of relapse as well as of treatment failure. on behalf of the Japan Society for Hematopoietic Cell Transplantation     

大剂量化疗不加全身放疗行自体骨髓移植治疗急性髓细胞性白血病

本文报告9例急性髓细胞性白血病在首次缓解期单用大剂量化疗不加全身放疗(TBI)行未净化自体骨髓移植(ABMT)治疗,经远期随访观察,结果有4例(44.4%)移植后分别已无病存活36、39、44和58个月,另5例(55.6%)则在移植后3.5～12.5个月时死于白血病复发。     

Recurrence of Autoimmune Disease after Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma

There have been a number of reports on the improvement of concomitant autoimmune disease (AID) after autologous hematopoietic stem cell transplantation (SCT) performed for hematologic malignancy. However, in some cases of hematologic malignancy with AID, exacerbation of AID after autologous SCT has been reported. We have treated 27 adults with multiple myeloma with single or tandem autologous SCT. After peripheral blood stem cells were collected and stored without CD34+ cell selection or T-cell depletion, all patients received melphalan (200 mg/m²) as a conditioning regimen. In 2 patients with a history of AID (one with rheumatoid arthritis [RA] and the other with bullous pemphigoid [BP]) and in 1 patient with Sjögren syndrome, AID recurred 7 to 12 months after autologous SCT.The RA and BP were in durable remission before SCT, and no Sjögren syndrome-related disease activity was clinically documented at the time of SCT. No progression of the myeloma was observed when the AIDs recurred.The patients required systemic steroid therapy for their AID, and successful control of the disease was achieved. Our experience suggests that autologous SCT with unmanipulated stem cells for myeloma is unlikely to cure preexisting AID; rather, the AID may worsen. Transplantation physicians should be aware of this possible complication.     

L-Asparaginase and Prednisolone Pretreatment Followed by Rubidomycin and Cytosine Arabinoside for Induction of Remission in Adult Patients with Acute Myeloblastic Leukaemia

77 unselected adult patients with acute myeloblastic leukaemia (AML), including practically all AML patients from an area with 1.9 million inhabitants, were randomized for either (1) 5 days pretreatment with l-asparaginase and prednisolone followed by a combination of rubidomycin and cytosine arabinoside (ARAP), or (2) treatment with a combination of rubidomycin, cytosine arabinoside and prednisolone without l-asparaginase pretreatment (RAP). Complete remission was induced with ARAP in 12 patients (31%) and with RAP in 13 patients (34%). Thus pretreatment with l-asparaginase did not improve the therapeutic response. The overall remission frequency was significantly higher below the age of 60; 50% compared to 13% above this age. Side-effects such as liver dysfunction, nausea and vomiting were more common in patients pretreated with l-asparaginase. Sterilization of the gut did not improve the remission frequency with either regime.     

A Study of Incidence and Characteristics of Infections in 476 Patients from a Single Center Undergoing Autologous Blood Stem Cell Transplantation

Infectious complications are a major cause of morbidity and mortality in patients who undergo autologous stem cell transplantation (ASCT). We examined 476 patients with hematologic malignancies (401) or solid tumors (75) who underwent ASCT between February 1990 and May 2005. Anti-infectious prophylaxis consisted of different combinations of ciprofloxacin, cotrimoxazole, fluconazole, aerosolized amphotericin B, acyclovir, and intravenous immunoglobulins. Overall, 454 patients (95%) developed fever in the first 60 days after ASCT. In the majority of patients, initial antibiotic therapy consisted of broad-spectrum beta-lactamic with or without amikacin. A glycopeptide was administered as initial therapy in 86 cases. Overall, there were 132 (29%) clinically documented infections (37 pneumonias), 79 (17%) microbiologically documented infections (65 bacteremias), and 243 (54%) fevers of unknown origin. Coagulase-negative staphylococci (18, 25%) and E coli (18, 25%) were the organisms most frequently isolated. The pattern of infection did not change throughout the study except for a significantly higher incidence of bacteremia due to gram-positive bacteria in the first 5 years of the study. Infection-related mortality was 5% (21 cases), with pneumonia the most frequent cause of death. ASCT should be considered a low-risk procedure, although new therapeutic approaches for patients developing severe respiratory infections are still needed.     

Successful Treatment of Primary Cardiac Lymphoma by Rituximab-CHOP and High-Dose Chemotherapy with Autologous Peripheral Blood Stem Cell Transplantation

Primary cardiac lymphoma (PCL) is defined as lymphoma involving only the heart and/or pericardium, or with an intrapericardial location of the main tumor mass. It is an extremely rare type of lymphoma and has a poor prognosis because of diagnostic delay and the disease site. PCL is histologically characterized by a mostly diffuse large B-cell lymphoma. The median survival time has been reported to be 7 months. We present the case of a 55-year-old woman who presented with chest oppression and dyspnea on effort. Following a close examination, PCL with a high International Prognostic Index was diagnosed. She received 6 courses of R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) and achieved complete remission. The patient then underwent a consolidation therapy consisting of high-dose chemotherapy including rituximab, followed by autologous peripheral blood stem cell transplantation. There were no complications, such as pulmonary embolism, fatal arrhythmia, or acute heart failure, throughout chemotherapy. Our experience indicates that this therapy is safe and effective and can improve the outcome of high-risk PCL.     

Graft-versus-host Disease Confined Solely to Intestine after Allogeneic Peripheral Blood Stem Cells Transplantation in a Patient with Chronic Myelogenous Leukemia

We describe a patient with chronic myelogenous leukemia who developing severe intestinal bleeding after allogeneic peripheral blood stem cells transplantation (allo-PBSCT). PBSC were obtained from an HLA one-locus mismatch sibling donor. On day 26 after PBSCT, although there was no sign of graft-versus-host disease (GVHD) in either the skin or the liver, diarrhea and severe intestinal bleeding occurred. The histopathological examination of the colon revealed complete denudation of the epithelial cells of the mucosa and no obvious apoptosis. Neither red cell fragments nor hemorrhagic diathesis was seen during this episode and the patient was diagnosed as having GVHD. Methylpredonisolone followed by FK506 may be effective in controlling intestinal bleeding and was used in our patient. Acute GVHD involving only the intestine has rarely been described but when using HLA-mismatched PBSCs, acute GVHD may occur severely and atypically.     

Risk Factors,Pattern and Clinical Outcome of Acute Graft Versus Host Disease in Acute Leukemia Patients Undergoing Allogeneic Stem Cell Transplant

We sought to determine risk factors, pattern and outcome of acute graft versus host disease (aGVHD) in seventy-seven acute leukemia patients who underwent allogeneic stem cell transplant at our centre from January 2008 to March 2013. GVHD prophylaxis with cyclosporine-methotrexate or cyclosporine-mycophenolate mofetil was used. Patients were divided in 2 groups, grade II-IV aGVHD (group A) and grade 0-I aGVHD (group B). Incidence of any grade and grade II-IV aGVHD was 44 and 18 %, respectively. The most common site of aGVHD was gastro-intestinal tract (65 %) followed by skin (35 %). Higher total nucleated cell (TNC) dose infused was associated with increased incidence of grade II-IV aGVHD. Incidence of relapse and incidence of slippage of chimerism was 21 and 36 % in group A while 37 and 27 % in group B respectively. Transplant related mortality (TRM) was 21 % in group A and 13 % in group B. Probability of OS and RFS at 4 years was 63 and 34 % in group A compared with 40 and 38 % in group B, respectively. We conclude that higher TNC dose infused is a risk factor for grade II-IV aGVHD with gut being the commonest site. Grade II-IV aGVHD did not have a significant impact on incidence of relapse, TRM and OS.     

A Long-term Remission of a Recurrent Acute Lymphoblastic Leukaemia with Donor Leukocyte Infusions after Allogeneic Peripheral Blood Stem Cell Transplantation

This case report describes a patient with recurrent and refractory acute lymphoblastic leukaemia (ALL-L3), who relapsed four months after a HLA identical allogeneic Peripheral Blood Stem Cell (PBSC) transplantation; he was treated after relapse with intensive chemotherapy and then he received leukocyte infusion from her sibling donor. A long term Complete Remission (CR) was achieved, with complete chimerism and without signs of chronic GVHD. Thirteen months after Donor Leukocyte Infusion (DLI), he developed a relapse (4% blasts in BM), and a second infusion of leukocytes with the same chemotherapy schedule was performed. Six months after the second DLI the patient is alive. Since responses to Donor Lymphocyte Infusions (DLI) are uncommon in ALL, the possible causative factors for this unusual response are discussed.     

Autologous Hematopoietic Stem Cell Transplantation for 3 Patients with Severe Juvenile Rheumatoid Arthritis

We performed autologous CD34+ stem cell transplantation in 3 patients with juvenile rheumatoid arthritis (JRA) refractory to conventional treatment. All patients had systemic type JRA. In case 1 (a 3-year-old boy), purified CD34+ cells from bone marrow were transplanted after a preconditioning regimen consisting of cyclophosphamide (200 mg/kg) and antithymocyte globulin (ATG) (40 mg/kg). However, the disease flared soon after transplantation. In case 2 (a 13-year-old girl) and case 3 (a 21-year-old woman), a preconditioning regimen consisting of etoposide (VP16) (2 g/m2), thiotepa (300 mg/m2), and ATG (40 mg/kg) was followed by transplantation of purified CD34+ stem cells harvested from peripheral blood mononuclear cells. The patients in cases 2 and 3 attained complete remission without any medication. Thus for patients with refractory JRA, autologous CD34+ cell transplantation appears to be a safe and feasible choice of treatment in terms of good quality of life. However, a greater number of patients and a longer observation period are needed before definitive conclusions can be drawn.     

Salvage Cord Blood Transplantation for Sustained Remission of Acute Megakaryoblastic Leukemia That Relapsed Early after Myeloablative Transplantation

Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia accompanied by an aggressive clinical course and dismal prognosis. We herein report a case of AMKL preceded by mediastinal germ cell tumor that relapsed early after allogeneic hematopoietic stem cell transplantation with myeloablative conditioning but was successfully treated using salvage cord blood transplantation (CBT) with reduced-intensity conditioning. Although several serious complications developed, sustained remission with a favorable general condition was ultimately achieved. Although an optimal therapeutic strategy remains to be established, the graft-versus-leukemia effect of CBT may be promising, even for the treatment of refractory AMKL.     

Ocular Manifestation of Acute Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation

A 26-year-old woman with acute myeloid leukemia underwent allogeneic peripheral blood stem cell transplantation from an HLA-identical brother. Eighteen days after transplantation, the patient developed grade II acute graft-versus-host disease (GVHD) and was treated with corticosteroids. On day 38, the patient complained of eye pain and lacrimation. A slitlamp examination revealed corneal ulcers and pseudomembranous formation in both eyes. Histologic and immunohistochemical examinations of the pseudomembrane disclosed an infiltrate dominated by T cells. A cytogenetic study of the pseudomembrane by fluorescence in situ hybridization identified a Y chromosome in the infiltrated mononuclear cells. Surveillance cultures from conjunctival swabs were negative. Thus, we diagnosed these ocular manifestations as an ocular involvement of acute GVHD.     

Successful Treatment with Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation in a Patient with Acute Myeloid Leukemia Complicated with Pulmonary Infection

We describe the case of a 48-year-old man with acute myeloid leukemia complicated with pulmonary infection that was successfully treated by nonmyeloablative allogeneic peripheral blood stem cell transplantation with conditioning by low-dose total body irradiation and fludarabine. The disease was diagnosed immunophenotypically as myeloid/natural killer cell precursor acute leukemia. After two courses of induction therapy, complete remission was achieved. However, the patient developed pneumonia from prolonged severe neutropenia. Nonmyeloablative allogeneic transplantation was performed because of the active pulmonary infection and the patient's poor performance status. Myelosuppression after transplantation was mild, and the pulmonary infiltration was well controlled during the course of treatment. At the time of this report the patient was an outpatient in our clinic, and on day 500, his disease was in remission with well-controlled chronic graft-versus-host disease. Nonmyeloablative transplantation may provide a new therapeutic strategy for treating patients with active infection who cannot tolerate conventional transplantation with high-dose chemoradiotherapy.     

L-Asparaginase Induced Durable Remission of Relapsed Nasal NK/T-Cell Lymphoma After Autologous Peripheral Blood Stem Cell Transplantation

A 60-year-old Japanese woman who presented with right nasal congestion and high fever was admitted to our hospital in March 1999. She was diagnosed with nasal NK/T-cell lymphoma clinical stage IVB. Because her NK/T-cell lymphoma was highly aggressive and chemo-resistant, she underwent autologous peripheral blood stem cell transplantation (PBSCT). The patient received a pretransplantation conditioning regimen of ranimustine, etoposide, carboplatin, and cyclophosphamide. On July 29, 1999, 1.0 x 10(6)/kg CD34+ cells were infused. The patient achieved first complete remission. In January 2000, NK/T-cell lymphoma relapsed in the skin and fever developed. CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisolone) was administered, resulting in partial regression of the skin lesions, but fever persisted. L-asparaginase (L-Asp) at a dose of 6,000 U/m2 per day was administered for 7 days, resulting in the complete disappearance of the skin lesions and resolution of the fever. The patient has been in second complete remission for more than 18 months since the completion of L-Asp treatment (as of July 2001).The effect of L-Asp in this patient was dramatic. Several cases have been reported describing the effectiveness of L-Asp in patients with nasal lymphoma and cutaneous T-cell lymphoma. A front-line chemotherapy regimen containing L-Asp for NK/T-cell lymphoma may warrant further evaluation.     

Refractory Crow-Fukase Syndrome (POEMS Syndrome) Successfully Treated with High-Dose Melphalan followed by Autologous Peripheral Blood Stem Cell Transplantation

Crow-Fukase syndrome (CFS) is a multisystemic disorder. Because it is characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, sclerotic bone lesions, and skin changes it is also known as POEMS syndrome. Extravascular volume overload is also one of the main symptoms. Uncontrollable extravascular volume overload is one of the major causes of death and one of the negative prognostic factors. Control of the extravascular volume overload is an important therapeutic strategy for this syndrome. We report here a case of CFS with extravascular volume overload resulting in pleural effusion and massive edema in the lower extremities, which was refractory to oral administration of melphalan and prednisolone. The patient's condition correlated with the serum level of vascular endothelial growth factor and markedly improved after administration of high-dose melphalan (200 mg/m²) followed by autologous peripheral blood stem cell transplantation. This approach should be considered in patients with CFS who fail to respond to conventional chemotherapy and have uncontrollable extravascular volume overload.