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M Kami

Publications and source records attributed to M Kami.

At least 37 records · Page 2Linked to original sources
PubMed2005

Comparison between reduced intensity and conventional myeloablative allogeneic stem-cell transplantation in patients with hematologic malignancies aged between 50 and 59 years.

To evaluate the efficacy of reduced-intensity stem-cell transplantation (RIST), we retrospectively compared outcomes of 207 consecutive Japanese patients aged between 50 and 59 years with hematologic malignancies who received RIST (n=70) and conventional stem-cell transplantation (CST) (n=137). CST recipients received total body irradiation (TBI)-based or busulfan/cyclophosphamide-based regimens. RIST regimens were purine analog-based (n=67), 2 Gy TBI-based (n=2), and others (n=1). Most CST recipients (129/137) received calcineurin inhibitors and methotrexate as graft-versus-host (GVHD) prophylaxis, while 32 RIST recipients received cyclosporin. In all, 23 CST and five RIST recipients died without disease progression within 100 days of transplant. Grade II to IV acute GVHD occurred in 56 CST and 38 RIST recipients. There was no significant difference in overall survival (OS) and progression-free survival between CST and RIST. On multivariate analysis on OS, five variables were significant: preparative regimens (CST vs RIST) (hazard ratio=1.92, 95% confidence interval, 1.25-2.97; P=0.003), performance status (2-4 vs 0-1) (2.50, 1.51-4.16; P<0.001), risk of underlying diseases (1.85, 1.21-2.83; P=0.004), acute GVHD (2.57, 1.72-3.84; P<0.001), and CML (0.38, 0.21-0.69; P=0.002). We should be careful in interpreting results of this small-sized retrospective study; however, reduced regimen-related toxicity might contribute to better survival in RIST. The low relapse rates following RIST suggest a strong antitumor activity through allogeneic immunity.

Female↗
PubMed2004

Feasibility of reduced intensity hematopoietic stem cell transplantation from an HLA-matched unrelated donor.

To evaluate the feasibility of reduced intensity stem cell transplantation (RIST) with bone marrow from a matched unrelated donor (MUD), we retrospectively investigated 20 patients with hematological disorders who received RIST in the Tokyo SCT consortium from January 2000 to October 2002. The preparative regimens were fludarabine-based (150-180 mg/m(2), n=18) or cladribine-based (0.77 mg/kg, n=2). To enhance engraftment, antithymocyte globulin (ATG) and 4 or 8 Gy total body irradiation (TBI) were added to these regimens in nine and 11 patients, respectively. GVHD prophylaxis was cyclosporine with or without methotrexate. In all, 19 achieved primary engraftment. Three developed graft failure (one primary, two secondary), and five died of treatment-related mortality within 100 days of transplant. Seven of the 19 patients who achieved initial engraftment developed grade II-IV acute GVHD, and seven of 13 patients who survived >100 days developed chronic GVHD. At a median follow-up of 5.5 months, estimated 1-year overall survival was 35%. Compared with a TBI-containing regimen, an ATG-containing regimen was associated with a high risk of graft failure (30 vs 0%, P=0.0737). This study supports the feasibility of RIST from MUD; however, procedure-related toxicities remain significant in its application to patients.

Adult↗
PubMed2004

Reduced-intensity stem cell transplantation from an HLA-identical sibling donor in patients with myeloid malignancies.

The purpose of this study was to evaluate the feasibility and efficacy of allogeneic hematopoietic stem cell transplantation with a reduced-intensity regimen (RIST) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). In all, 36 patients (median age 55 years) underwent RIST from an HLA-matched related donor between September 1999 and December 2002. The diagnoses included AML (n=14), leukemia evolving from MDS (n=10), and MDS (refractory anemia with excess blasts n=6, refractory anemia n=6). The RIST regimen consisted of purine analog (cladribine or fludarabine)/busulfan, with or without antithymocyte globulin. The regimen was well tolerated, and 34 patients achieved durable engraftment and most achieved remission after RIST. A total of 17 patients developed grade II-IV acute GVHD, and 27 developed chronic GVHD. Eight patients relapsed, and five of them received antithymocyte globulin (ATG) as part of the preparative regimen. A total of 12 patients died (four disease progression, six transplantation-related complications, and two others). Estimated 1-year disease-free survival (DFS) in low- and high-risk groups was 85 and 64%, respectively. We conclude that RIST can be performed safely in elderly patients with myeloid malignancies, and has therapeutic potential for those who fail conventional chemotherapy. In view of the significant association between GVHD or ATG and DFS, defined management of GVHD following RIST should become a major target of clinical research.

Adult↗
PubMed2004

A nationwide survey of deep fungal infections and fungal prophylaxis after hematopoietic stem cell transplantation in Japan.

We conducted a nationwide survey to define incidence of deep fungal infections and fungal prophylaxis practices after HSCT. In all, 63 institutions responded. Total number of in-patient transplantations was 935: 367 autologous, 414 allogeneic myeloablative, and 154 allogeneic reduced-intensity (RIST) (n=154). Number of patients who were cared for in a clean room at transplant was 261 (71%) in autologous, 409 (99%) in conventional and 93 (66%) in RIST, respectively. All patients received prophylactic antifungal agents; 89% fluconazole. Number of patients who received the dosage recommended in the CDC guidelines (400 mg/day) was 135 (42%) in conventional transplant and 34 (30%) in RIST (P=0.037). Number of patients who received fluconazole until engraftment and beyond day 75 in conventional transplant vs RIST was, respectively, 324 (100%) vs 109 (97%), and 39 (12%) vs 18 (16%), with no significant difference between the two groups. A total of 37 patients (4.0%) were diagnosed with deep fungal infections; autologous transplantation (0.03%), conventional transplantation (6.0%) and RIST (7.1%). Wide variations in antifungal prophylaxis practice according to the type of transplant and the institutions, and deep fungal infection remain significant problems in RIST.

Antifungal Agents↗
PubMed2004

Clinical impact of graft-versus-host disease against leukemias not in remission at the time of allogeneic hematopoietic stem cell transplantation from related donors. The Japan Society for Hematopoietic Cell Transplantation Working Party.

Acute graft-versus-host disease (GVHD) increases post-transplant mortality and morbidity, but exerts a potent graft-versus-leukemia (GVL) effect. To clarify the impact of GVHD on outcome after transplant in aggressive diseases, patients with acute myeloid or lymphoblastic leukemia (AML, n = 366 or ALL, n = 255) in nonremission states, or chronic myelogenous leukemia (CML, n = 180) in accelerated phase (AP) or blastic crisis (BC), who received allogeneic hematopoietic stem cell transplantation (HSCT) from a related donor between 1991 and 2000, were analyzed. Significant improvement in overall and disease-free survival (DFS) was detected with grade I acute GVHD in AML (P = 0.0002 for overall survival and 0.0009 for DFS, respectively) and in CML (P = 0.0256 and 0.0366, respectively), while the trend towards improved survival was observed in ALL. Relapse rate was lower in grade I acute GVHD than in grade II in all three diseases, suggesting that treatment for grade II GVHD may compromise the GVL effect associated with GVHD. Chronic GVHD was found to suppress relapse in CML and ALL, but not in AML, although no improvement in survival was observed in any disease category. Our results suggest that treatment for grade II acute GVHD may need to be attenuated in transplant for refractory leukemias.

Adolescent↗
PubMed2004

Regimen-related toxicity following reduced-intensity stem-cell transplantation (RIST): comparison between Seattle criteria and National Cancer Center Common Toxicity Criteria (NCI-CTC) version 2.0.

Acute regimen-related toxicity (RRT) is minimal in reduced-intensity stem-cell transplantation (RIST). However, the Seattle RRT grading (Bearman et al), developed in the context of conventional-intensity transplantation, is frequently applied to RIST. We compared the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0 with the Seattle criteria after RIST in 86 patients. RRT within 30 days of transplant graded by both sets of criteria were significantly associated with the outcome confirming the predictive value of both the systems. A total of 15 patients died of disease progression, and 12 of transplant-related mortality: RRT (n = 2), graft-versus-host disease (GVHD) (n = 7), infection (n = 1), and others (n = 2). GVHD-related deaths primarily resulted from infections after steroid treatment (n = 6) and bronchiolitis obliterans (n = 1). This study shows that NCI-CTC is appropriate in toxicity evaluation of RIST, and that its application to RIST enables a toxicity comparison between RIST and other types of cancer treatments. Since GVHD is a significant problem in RIST, modifications are required to evaluate immunological complications following RIST.

Graft vs Host Disease↗
PubMed2003

Successful treatment of meningoencephalitis caused by methicillin-resistant Staphylococcus aureus with intrathecal vancomycin in an allogeneic peripheral blood stem cell transplant recipient.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common infectious pathogen during stem cell trans-plantation. We report a case of meningoencephalitis with multiple abscess formation caused by MRSA, which occurred in a 4-year-old boy soon after allogeneic peripheral blood stem cell transplantation. We successfully cured the infection with a combination of intravenous and intrathecal vancomycin.

Anti-Bacterial Agents↗
PubMed2003

High complete response rate after allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimens in advanced malignant lymphoma.

The possible advantage of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a graft-versus-lymphoma effect. We explored the feasibility and efficacy of allo-HSCT with reduced-intensity (RI) regimens in advanced malignant lymphoma (ML). A total of 20 patients with indolent (n=9) or aggressive lymphoma (n=11) received allo-HSCT with an RI regimen (RIST). The preparative regimen consisted of a combination of purine analog and alkylating agent with or without antithymocyte globulin. A total of 11 patients had chemorefractory disease, seven had chemosensitive relapsed disease and two had residual disease. All of the patients received G-CSF-mobilized blood stem cells from HLA-matched siblings. Of the 20 patients, 19 achieved engraftment with acceptable regimen-related toxicities. Seven patients developed grade II-IV acute GVHD and 15 developed chronic GVHD. Of the 15 patients with evaluable disease, 12 achieved a complete response. One died of invasive fusariosis, four subsequently died of GVHD complicated with fungal infection and one died of progressive disease. With a median follow-up of 358 days, the Kaplan-Meier estimates for 1-year overall and progression-free survival were both 70%. The high response rate with low relapse observed in this study suggests that RIST may be an effective alternative curative treatment for patients with advanced ML.

Adult↗
PubMed2003

Induction of graft-versus-autoimmune (GVA) disease effect against refractory psoriasis by complete donor-type chimerism and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

A 67-year-old man with AML, who had a 21-year history of psoriasis without remission, received a reduced-intensity transplantation from an HLA-identical sibling. The preparative regimen consisted of busulfan and fludarabine. Graft-versus-host-disease (GVHD) prophylaxis was cyclosporine and methotrexate. Psoriasis was completely resolved on day 18. The subsequent clinical course was uneventful until day 42, when psoriasis recurred at the same sites as before RIST. Peripheral blood examined on day 63 showed mixed chimerism with 54% recipient type. Cyclosporine was rapidly tapered off over the next 2 weeks. On day 90, 100% donor-type chimerism was confirmed. Subsequently, psoriasis improved simultaneously with the occurrence of mucositis and rash as a manifestation of GVHD. Scattered erythematous patches of psoriasis disappeared again by day 105. We initiated 0.5 mg/kg prednisolone on day 119, and resumed cyclosporine on day 133. At 7 months after RIST, he still suffers from chronic GVHD, but his psoriasis remains in remission for the first time in 21 years. The anti-psoriasis effect of the conditioning is mild and transient, while the graft-versus-autoimmunity effect, related to the induction of complete donor-type chimerism and GVHD, is more profound and persisting. A graft-versus-autoimmunity effect lies in the delicate balance between alloimmunity and immunosuppressant used for GVHD prophylaxis/treatment.

Aged↗
PubMed2003

Immune reconstitution following reduced-intensity transplantation with cladribine, busulfan, and antithymocyte globulin: serial comparison with conventional myeloablative transplantation.

The primary object of the conditioning regimen for allogeneic reduced-intensity stem cell transplantation (RIST) is immunosuppression to achieve stable engraftment of donor cells, rather than bone marrow ablation. Therefore, immune reconstitution after RIST might be different from that after conventional stem cell transplantation (CST). In this study, 22 patients underwent RIST and 28 underwent CST. The RIST regimen consisted of cladribine (2-CdA; 0.11 mg/kg/day for 6 days), BU (4 mg/kg/day for 2 days), and rabbit anti-thymocyte globulin (ATG; 2.5 mg/kg/day for 2-4 days). The CST group received either the BU (4 mg/kg/day x 4 days)/CY (60 mg/kg/day x 2 days) (n=13) or CY (60 mg/kg/day x 2 days)/TBI (4 Gy/day x 3 days) regimen (n=15). All patients underwent transplantation with G-CSF-mobilized blood stem cells. Engraftment speed after RIST was fast and seven of 22 patients did not require platelet transfusion. We noted that the numbers of CD4+, CD4+CD45RA+, and CD4+CD45RO+ T cells after transplant in the RIST group were significantly lower than those in the CST group (P=0.0001 for both the comparisons). However, the reconstitution of CD20+ B cells was faster in the RIST group (P=0.0001). The response of T cells to PHA stimulation was lower in the RIST group (P=0.0001 on day 30 and P=0.02 on day 90). Nevertheless, there were no significant differences in the incidence of bacterial, fungal, or viral infections between the two groups. We concluded that our RIST regimen might delay laboratory-evaluated T-cell immune reconstitution compared to CST; however, the observed setbacks did not directly translate into clinically significant increases in infectious episodes.

Adolescent↗
PubMed2003

Late hemorrhagic cystitis after reduced-intensity hematopoietic stem cell transplantation (RIST).

We reviewed medical records of 256 patients to investigate the frequency and characteristics of hemorrhagic cystitis (HC) associated with reduced-intensity stem cell transplantation (RIST) as opposed to conventional stem cell transplantation (CST); 137 patients underwent CST and 119 RIST. Diagnosis of HC was made based on two or more episodes of sterile, macroscopic hematuria with normal coagulation profiles, without any evidence of renal stones or genitourinary malignancy. Actuarial frequency of HC development in RIST group was 7.6% (9/119), which gave a cumulative annual incidence of 11.7%. In CST group, 13 of 137 patients (9.5%) developed HC, giving an estimated annual incidence of 9.7%. The probability of developing HC was similar between the two groups (P=0.77). The viral etiologies of HC, adenovirus (n=12) and BK virus (n=2), were documented in eight patients after RIST and in six after CST. HC was milder and of a shorter duration, with less blood transfusion requirements, in RIST group than in CST group. A multivariate analysis revealed that HC was associated with antiadenovirus antibody positivity in the recipients, total dose of busulfan, and chronic GVHD. Although HC following RIST is less severe than that following CST, it is still a significant problem.

Adenoviridae↗
PubMed2002

Primary cutaneous aspergillosis caused by Aspergillus ustus following reduced-intensity stem cell transplantation.

A 19-year-old woman with myelodysplastic syndrome underwent reduced-intensity stem cell transplantation [RIST: (cladribine 0.11 mg/kg for 6 days, busulfan 4 mg/kg for 2 days, and rabbit antithymocyte globulin)] from her one HLA-mismatched mother. Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine A (CSA) alone. Severe acute GVHD in the skin, gut, and liver developed concurrently with stable engraftment, and methylprednisolone was administered (1-2 mg/kg per day, then pulse therapy with 1 g/day for 3 days) until day 40 of transplant, when a necrotic lesion of 10 mm in diameter appeared on the right cheek. The initial skin biopsy of the affected area showed a nonspecific inflammatory change. Routine X-ray and computed tomography examinations of the sinuses, chest, and abdomen disclosed no particular abnormalities. Despite intensive antibiotic therapy, the lesion rapidly extended to form an ulcer. A second biopsy specimen obtained from the lesion showed massive septa hyphae, suggesting mold infection. Although we immediately started amphotericin B, she died of multiorgan failure on day 68. Postmortem DNA sequence analysis of the specimen using the polymerase chain reaction identified Aspergillus ustus. Although this is an extremely rare complication after transplantation, this case highlights that we should pay more attention to primary cutaneous aspergillosis in severely immunosuppressed patients.

Adult↗
PubMed2002

Severe regimen-related toxicity occurring in a patient with XYY syndrome receiving allogeneic peripheral blood stem cell transplantation.

A 23-year-old man with chronic myelocytic leukemia (CML) in the first chronic phase underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-identical sibling. Pretransplant evaluations showed that he had a low risk of transplantation-related mortality and that the interval between the diagnosis of CML and PBSCT was only 6 months. However, he developed a variety of complications, including acute renal failure requiring hemodialysis, severe hepatic damage, hemorrhagic cystitis, and gastrointestinal hemorrhage leading to hypovolemic shock. Pathological examination of the colonic mucosa showed vascular endothelial damage and thrombotic lesions, leading to the diagnosis of thrombotic microangiopathy. Later, we found that he had the constitutional abnormality XYY. XYY syndrome is a frequent congenital abnormality, and mental disorders and congenital abnormalities of kidney and liver are common manifestations. Considering his clinical course, it was interesting that complications were severe in the organs which are frequently involved in cases of XYY syndrome. These organs may have poor function or poor reserves and may be more vulnerable to endothelial damage caused by high-dose cytotoxic chemotherapy. Patients with XYY syndrome might have a high risk of transplantation-related mortality.

Adult↗
PubMed2002

Suspected delayed immune recovery against cytomegalovirus after reduced-intensity stem cell transplantation using anti-thymocyte globulin.

A reduced-intensity hematopoietic stem cell transplantation (RIST) regimen was developed to induce immunosuppression to facilitate the engraftment of donor cells. However, there have been concerns that the incidence of opportunistic infection may increase after this procedure. To address this problem, we retrospectively analyzed the medical records of 24 RIST recipients who were treated over a recent 16-month period for comparison with 31 recipients of conventional allogeneic transplantation (CST). The RIST regimen consisted of cladribine (0.66 mg/kg), busulfan (8 mg/kg), and rabbit anti-thymocyte globulin (ATG; 5-10 mg/kg). All of the patients received allogeneic peripheral blood stem cells from an HLA-identical or one-locus mismatched related donor. Although the incidence of positive CMV antigenemia was comparable between the two groups (58% vs 68%), RIST patients developed positive antigenemia significantly sooner than did CST patients (P = 0.01) and showed higher initial and maximum antigenemia values (P = 0.026 and P = 0.003, respectively). These findings may suggest that immune recovery against CMV was delayed after our RIST procedure, but this did not directly translate into an increase in clinically significant CMV disease. Early therapeutic intervention with ganciclovir might play a role in preventing the progression of early CMV infection to CMV disease.

Adolescent↗
PubMed2002

Successful allogeneic blood stem cell transplantation for aplastic anemia in a patient with renal insufficiency requiring dialysis.

A 27-year-old man with aplastic anemia and renal insufficiency requiring dialysis underwent allogeneic PBSCT. The preparative regimen consisted of melphalan, ATG and TLI. GVHD prophylaxis consisted of cyclosporine and prednisolone. He was dialyzed prior to administration of melphalan and at 24 and 72 h after it. Otherwise, the dialysis schedule was unchanged, at three times a week. Engraftment was rapid. Regimen-related toxicity was minimal. Pharmacokinetic parameters of melphalan were not significantly altered with its plasma half-life 1.5 h. Patients with renal failure can receive allogeneic HSCT, and a combination of melphalan, ATG and TLI may serve as an alternative to CY and ATG.

Adult↗