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A Maruta

Publications and source records attributed to A Maruta.

At least 19 recordsLinked to original sources
PubMed2005

Myeloablative allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: significant roles of total body irradiation and chronic graft-versus-host disease.

Disease-free survival in Philadelphia chromosome-positive ALL (Ph + ALL) is very poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently considered the only procedure with curative potential. To identify factors affecting transplant outcome, we analyzed the data from 197 Ph + ALL patients aged 16 years or older who had undergone allo-HSCT. The 5-year survival rates were 34% for patients in first complete remission (CR), 21% for those in second or subsequent CR, and 9% for those with active disease (P < 0.0001). Multivariate analysis showed four pre-transplant factors as significantly associated with better survival: younger age, CR at the time of transplantation, conditioning with total body irradiation, and HLA-identical sibling donor (P < 0.0001, P < 0.0001, P = 0.0301, P = 0.0412, respectively). Severe acute GVHD increased the risk of treatment-related mortality (TRM) without diminishing the risk of relapse, whereas chronic GVHD reduced the risk of relapse without increasing the risk of TRM. Thus, patients who developed extensive chronic GVHD had better survivals (P = 0.0217), and those who developed grade III-IV acute GVHD had worse survivals (P = 0.0023) than did the others.

Adolescent↗
PubMed2005

Human herpesvirus-6 encephalitis after unrelated cord blood transplantation.

Here we describe 2 patients with acute leukemia in whom human herpesvirus-6 (HHV-6) encephalitis developed after cord blood transplantation. In patients 1 and 2, generalized seizure and coma developed on day 62 and day 15, respectively, after cord blood transplantation, which failed to engraft in patient 1. Magnetic resonance imaging (MRI) of patient 1's brain showed low-intensity signals at the gyri of the bilateral lateral lobes on T1-weighted images and high-intensity signals on T2-weighted images. MRI of patient 2's brain showed high-intensity signals in bilateral white matter on T2-weighted images and on fluid-attenuated inversion recovery (FLAIR) images. Cerebrospinal fluid examination revealed an increased protein level with pleocytosis in patient 1 and a normal protein level without pleocytosis in patient 2. Polymerase chain reaction analysis detected HHV-6 DNA in the cerebrospinal fluid of both patients. Patient 1 recovered after administration of gancyclovir for 3 weeks. However, she again suffered from encephalitis after discontinuation of gancyclovir, and died of sepsis. Patient 2 died from an anoxic brain caused by generalized seizure. When neurological symptoms and signs appear in hematopoietic stem cell transplantation recipients, we should consider HHV-6 encephalitis and promptly and empirically treat them with gancyclovir or foscarnet.

Adult↗
PubMed2004

Thiotepa/cyclophosphamide/TBI as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome.

In all, 18 patients (30-56 years; median 49) with MDS underwent allogeneic HSCT from related (n=12) or unrelated (n=6) donors after a conditioning regimen comprising thiotepa, cyclophosphamide, and TBI. GVHD prophylaxis consisted of cyclosporine (n=15) or tacrolimus (n=3) with short-course methotrexate. Four patients had low-risk disease (refractory anemia or complete remission after chemotherapy) and 14 patients had high-risk disease (RAEB, RAEB-t, or AML). Grade II-IV acute GVHD developed in six patients and chronic GVHD in 10. With a median follow-up of 31 months, the 2-year survival probability is 75% for low-risk patients and 57% for high-risk patients. One patient died of leukemia and six of treatment-related causes. This conditioning regimen requires further study in patients with MDS.

Adult↗
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

Effect of graft-versus-host disease on the outcome of bone marrow transplantation from an HLA-identical sibling donor using GVHD prophylaxis with cyclosporin A and methotrexate.

The effect of graft-versus-host disease (GVHD) on relapse incidence and survival has been analyzed in several studies, but previous studies included heterogeneous patients. Therefore, we analyzed the data of 2114 patients who received unmanipulated bone marrow graft from an HLA-identical sibling donor with a GVHD prophylaxis using cyclosporin A and methotrexate. Among the 1843 patients who survived without relapse at 60 days after transplantation, 435 (24%) developed grade II-IV acute GVHD. Among the 1566 patients who survived without relapse at 150 days after transplantation, 705 (47%) developed chronic GVHD. The incidence of relapse was significantly lower in patients who developed acute or chronic GVHD, but disease-free survival (DFS) was significantly inferior in patients who developed acute GVHD. A benefit of 'mild' GVHD was only seen in high-risk patients who developed grade I acute GVHD. The strongest association between GVHD and a decreased incidence of relapse was observed in patients with standard-risk acute myelogenous leukemia/myelodysplastic syndrome. In conclusion, the therapeutic window between decreased relapse and increased transplant-related mortality due to the development of GVHD appeared to be very narrow.

Adult↗
PubMed2001

Severe cardiac toxicity in hematological stem cell transplantation: predictive value of reduced left ventricular ejection fraction.

Eighty patients receiving hematological stem cell transplantation (HCT) with a preparative regimen consisting of total body irradiation (12.5 Gy), cyclophosphamide (4000 or 4500 mg/m2), and thiotepa (400 mg/m2) were evaluated for the development of cardiac toxicity. Patients in whom the pretransplant cumulative dose of anthracycline was more than or equal to 300 mg/m2 showed a lower left ventricular ejection fraction (EF) before HCT compared to patients with less than 300 mg/m2 (0.61 +/- 0.09 vs 0.67 +/- 0.06, P = 0.0010). Patients who had undergone more than or equal to six courses of chemotherapy showed a decreased EF before HCT compared to those after less than six courses (0.67 +/- 0.05 vs 0.63 +/- 0.09, P = 0.03). Three of seven patients (43%) whose pretransplant EF had been less than or equal to 0.55 developed severe cardiac toxicity, characterized by congestive heart failure (CHF) compared with none of 83 patients (0%) whose pretransplant EF had been more than 0.55 (P = 0.00026). Of the three patients who developed severe cardiac toxicity, two were given more than 300 mg/m2 of cumulative anthracycline and underwent 23 courses and six courses of chemotherapy, while the other patient received only two courses of chemotherapy with a total dose of 139 mg/m2 of anthracycline. These results indicate that an increased cumulative dose of anthracycline and number of chemotherapy treatments are correlated with a decrease of the EF and that the EF before HCT is useful for predicting the risk of cardiac complications for recipients who have received chemotherapy.

Adolescent↗
PubMed2001

Immune reconstitution assessed during five years after allogeneic bone marrow transplantation.

Immune reconstitution is an important component of successful allogeneic bone marrow transplantation. Immune reconstitution was evaluated for 5 years after transplantation. While the number of CD8+ T cells and CD56+ cells recovered early post transplantation, a low number of CD4+ and CD4+ CD45RA+ T cells and reversal of the CD4/CD8 ratio continued up to 5 years. Although early recovery of IgG and IgM was seen at day 100 post transplantation, serum concentration of IgA was below the normal range at 6 months and increased gradually up to 5 years. Development of acute GVHD did not affect the numbers of CD4+, CD8+, CD4+ CD45RA+ and CD4+ CD29+ T cells, but the number of CD56+ cells in patients who developed grades II-IV acute GVHD was low. The number of CD4+ CD29+ T cells had a tendency to be higher in the patients with extensive chronic GVHD than in those without chronic GVHD 2 years after transplantation whereas the number of CD4+ CD45RA+ T cells was low in spite of the absence of chronic GVHD. Serum concentration of IgA was lower in patients with extensive chronic GVHD than in those without chronic GVHD at 180 days. The number of CD4+ CD45RA+ cells in 10-19-year-old patients was higher than that in 40-49-year-old patients. Response to the Con A and PHA in 10-19-year-old patients was higher than that in older patients at 1 and 2 years. There was no significant difference in the ability of immune reconstitution between related transplant recipients and unrelated transplant recipients. These results suggest that chronic GVHD and age of patients affected immune reconstitution post transplant.

Adolescent↗
PubMed2001

Donor leukocyte infusion for Japanese patients with relapsed leukemia after allogeneic bone marrow transplantation: indications and dose escalation.

To clarify the role of dose escalation of donor leukocyte infusion (DLI) in the treatment of relapsed leukemia after allogeneic bone marrow transplant (BMT), data from 100 patients were collected from 46 facilities in Japan and analyzed with respect to indications and infused cell dose. Complete remission (CR) was achieved in 11 of 12 (91%) patients with relapsed chronic myelogenous leukemia (CML) in the chronic phase, 3 of 11 (27%) with CML in the acute phase, 8 of 21 (38%) with acute myelogenous leukemia (AML), 6 of 23 (25%) with acute lymphoblastic leukemia (ALL), and 5 of 11 (45%) with myelodysplastic syndrome (MDS). The probability of remaining in CR at 3 years was 82% in CML patients in the chronic phase, but 0% in those with CML in the acute phase, 7% in those with AML, 0% with ALL, and 33% with MDS. Acute graft-versus-host disease (GVHD) (> or = 2) developed in 31 of 89 (34%) patients with human leukocyte antigen identical related donors and was fatal for 7 (7%). A leukocyte dose of 1 x 10(7)/kg of recipient body weight with CML in the chronic phase, 3 x 10(7)/kg of recipient body weight with MDS, and 1 x 10(8)/kg of recipient body weight with acute leukemia appeared to be optimal as an initial dose of DLI. However, the minimal dose of leukocyte developing fatal GVHD was 7 x 10(7)/kg of recipient body weight. These suggest that a relatively small dose of DLI ranging from 1 x 10(7)/kg to 5 x 10(7)/kg of recipient body weight should be administered initially then the infused escalating dose 2 or 3 months later in patients with CML in the chronic phase and MDS. However, a large number of leukocytes around 1 x 10(8)/kg are needed to induce graft versus leukemia effects in patients with acute leukemia despite a 7% fatality in GVHD.

Adolescent↗
PubMed2001

Granulomatous tubulointerstitial nephritis induced by all-trans retinoic acid.

We report the first case of granulomatous tubulointerstitial nephritis induced by all-trans retinoic acid (ATRA) in a patient with acute promyelocytic leukemia (APL). Acute renal failure during treatment with ATRA has been previously reported as a part of an ATRA syndrome or a thrombotic complication of a hypercoagulable state. This case indicates an alternative mechanism of acute renal failure occurring during ATRA therapy.

Aged↗
PubMed2001

[Sequential analysis of p210- and p190-bcr-abl by RT-PCR after allogeneic bone marrow transplantation for p210/p190-bcr-abl double positive acute lymphoblastic leukemia].

In patients with both p210-bcr-abl (p210) and p190-bcr-abl (p190)-positive acute lymphoblastic leukemia, the number of p190 transcripts is lower than that of p210 transcripts. It is speculated that the p190 transcript occurs as a consequence of alternative splicing or missplicing events in the BCR gene. Four patients with both p210- and p190-positive acute lymphoblastic leukemia were studied for expression of p210 and p190 by RT-PCR before and after allogeneic bone marrow transplantation. p190 negativity was documented in all four patients, followed by p210 negativity one to two months later in three patients. These results suggest that negativity for p190 indicates an ongoing decrease in the small number of residual leukemic cells. In one patient p190 appeared transiently in spite of prolonged negativity for p210 18 months after bone marrow transplantation. We conclude that analysis of p210 and p190 is useful for following up patients with both p210- and p190-positive acute lymphoblastic leukemia.

Adult↗
PubMed2001

[Complete cytogenetic response obtained with unrelated donor lymphocyte infusion for relapse of chronic myeloid leukemia in blastic crisis after allogeneic bone marrow transplantation].

A 35-year-old man with chronic myeloid leukemia (CML) in blastic crisis (BC) received an allogeneic bone marrow transplant from an unrelated donor in October 1998 after three cycles of chemotherapy. BC relapse developed on day 349 after transplantation. After one cycle of chemotherapy and treatment with interferon, the patient received donor lymphocyte infusion (DLI), and this resulted in a complete cytogenetic response 21 days later. Grade III acute graft-versus-host disease developed on day 25 after DLI, but this was resolved after administration of prednisolone. Disease relapse occurred at extramedullary sites on day 162 after DLI, and the patient died of sepsis after receiving chemotherapy. This case illustrates that unrelated DLI can induce remission successfully in patients with relapse of CML in BC through a graft-versus-leukemia effect.

Adult↗
PubMed2001

[Feasibility of early tapering and discontinuation of cyclosporine to intensify the graft-versus-leukemia effect in patients with advanced hematologic neoplasms].

Twenty patients with advanced hematological malignancies at high risk of relapse who had each received a bone marrow transplant from a matched sibling were registered between October 1996 and January 2000. Cyclosporine (CSP) was tapered on day 40 and stopped on day 50 in 10 patients without prior grade II-IV acute graft-versus-host disease (GVHD), relapse or active infection. These patients were eligible for early tapering of CSP. Although grade II/III acute GVHD was observed in three patients and chronic GVHD in eight patients after CSP tapering, no patients died of GVHD. Three patients died due to disease relapse and one patient died of idiopathic interstitial pneumonia while in remission. The probability of event-free survival at 2 years was 60%. These result indicate that early tapering and withdrawal of CSP is feasible and may provide a graft-versus-leukemia effect in patients with advanced leukemia.

Adult↗
PubMed2000

Strong inverse correlation between serum TPO level and platelet count in essential thrombocythemia.

Serum thrombopoietin (TPO) levels in 50 essential thrombocythemia (ET) patients were measured using a highly sensitive sandwich ELISA. In nine cases, TPO levels were measured at two points with different platelet counts. ET patients showed significantly higher serum TPO levels (n = 59, 2.70 +/- 2.74 fmol/mL, P < 0.0001) than those of normal individuals (n = 29, 0.83 +/- 0.36 fmol/mL). Twenty-three previously untreated ET patients also showed significantly higher serum TPO levels (1.33 +/- 0.75 fmol/mL, P = 0.0066) than normal individuals. Extremely high serum TPO levels (5.46 +/- 3.68 fmol/mL) were observed in ET patients with normal platelet counts. Furthermore, a strong inverse correlation was found between serum TPO levels and platelet counts in ET patients (R = -0.729, P < 0. 0001). This inverse correlation also held for each of nine cases with two-point TPO measurements. In the clinical course of ET, megakaryocyte mass may parallel the platelet mass before and after chemotherapy. Although it is unknown whether overproduction of TPO exists or not in ET, total platelet and megakaryocyte mass, i.e., the total number of c-Mpl, may play a role to regulate serum TPO levels.

Adult↗
PubMed2000

The Japanese multicenter open randomized trial of ursodeoxycholic acid prophylaxis for hepatic veno-occlusive disease after stem cell transplantation.

Hepatic veno-occlusive disease (VOD) is a common transplant-related complication of stem cell transplantation. There is no safe and proven therapy for established VOD, and attempts have focused on its prevention. Limited studies have suggested that prophylactic use of ursodeoxycholic acid (UDCA) reduced the incidence of VOD. To confirm the preventive effect of UDCA on VOD, we conducted a prospective, unblinded randomized, multicenter study of UDCA involving 132 patients who underwent stem cell transplantation for a variety of disorders. Sixty-seven patients were assigned to the UDCA-treated group, and 65 patients were assigned to the control group. The clinical characteristics of the two groups were similar with respect to primary diagnosis, age, sex, and baseline organ function. The preparative regimen and GVHD prophylaxis did not differ significantly between the two groups. UDCA was highly effective in preventing VOD, which occurred in only 3.0% in the UDCA-treated group, as opposed to 18.5% in the control group (P = 0.0043). There were no adverse effects attributable to UDCA. The initial promising report of a prophylactic effect of UDCA on VOD after stem cell transplantation was confirmed in this prospective study.

Adult↗
PubMed2000

Donor leukocyte infusion for Japanese patients with relapsed leukemia after allogeneic bone marrow transplantation: lower incidence of acute graft-versus-host disease and improved outcome.

To clarify the role of donor leukocyte infusion (DLI) in the treatment of leukemia relapsing after allo-BMT, data from 100 patients were collected from 46 facilities in Japan and analyzed with respect to the efficacy and adverse effects of donor leukocyte infusion. Complete remission was achieved in 11 of 12 (91%) patients with relapsed chronic myelogenous leukemia (CML) in chronic phase, three of 11 (27%) with CML in the acute phase, eight of 21 (38%) with acute myelogenous leukemia (AML), six of 23 (25%) with acute lymphoblastic leukemia (ALL) and five of 11 (45%) with myelodysplastic syndrome (MDS). The probability of remaining in CR at 3 years was 82% in CML patients in the chronic phase, but 0% in those with CML in the acute phase, 7% in those with AML, 0% with ALL and 33% with MDS. Acute GVHD (>/=2) developed in 31 of 89 (34%) patients with HLA-identical related donors and was fatal for seven (7%). Cytopenia developed in 21 of 94 (22%) with no associated fatalities. When the outcome of patients with CML in CP and MDS was analyzed, development of GVHD, cytopenia, or both, was associated with a higher GVL effect (15 of 16, 93%) than in those without adverse affects (one of 6, 17%). A leukocyte dose of 5 x 107/kg of recipient body weight appeared to be optimal as an initial dose of DLI. Given the relatively low incidence of acute GVHD and the similar GVL effect, DLI may be more beneficial to patients in Japan with recurrent leukemia than to those in Western countries. Bone Marrow Transplantation (2000) 26, 769-774.

Acute Disease↗
PubMed2000

Predictive factors for central nervous system involvement in non-Hodgkin's lymphoma: significance of very high serum LDH concentrations.

Factors predictive for central nervous system (CNS) involvement at presentation were investigated in 152 patients with non-Hodgkin's lymphoma (NHL) except for lymphoblastic cell lymphoma and small noncleaved cell lymphoma. Twelve patients developed CNS involvement during their disease course. The incidence was 7.9% of all the patients studied and 17.0% of the patients with serum LDH concentration > or = two times the upper limit of normal (2N). By univariate analysis, stage IV disease (P = .023), a serum LDH concentration > or = 2 N (P = .009), and bone marrow involvement (P = .016) were risk factors for CNS involvement. Multivariate logistic regression analysis identified a serum LDH concentration > or = 2 N (P = .032) as an independent predictor for CNS involvement. All 12 patients who developed CNS involvement were among the 126 patients with diffuse lymphoma, whereas none of the 17 patients with follicular lymphoma developed CNS involvement, although the difference was not statistically significant. The median survival of the patients with CNS involvement was only 4.5 months. We conclude that a serum LDH concentration > or = 2N at presentation is a significant predictive factor for CNS involvement for NHL patients without lymphoblastic lymphoma and small noncleaved cell lymphoma. Therefore, we would suggest that CNS prophylaxis should be considered for patients with a serum LDH concentration > or = 2N at presentation and diffuse lymphoma once a complete remission is achieved.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Therapy-related leukemia and myelodysplastic syndrome: a large-scale Japanese study of clinical and cytogenetic features as well as prognostic factors.

It is known that alkylating agents and topoisomerase II inhibitors can cause distinct forms of therapy-related leukemia and myelodysplastic syndrome (TRL/MDS). Although several reports have been made on each of these agents separately, no study has yet been conducted to evaluate the effect of these two types of agents in the same population. In a nationwide, large-scale population study, the clinical and cytogenetic features as well as the prognostic factors in 256 patients with TRL/MDS were assessed. Median age was 61 years, and the median period of latency from primary malignancies was 47.9 months. The latency period was significantly shorter in patients undergoing chemotherapy, especially that of topoisomerase II inhibitors, for primary cancer. The morphological diagnosis of TRL/MDS was acute myeloid leukemia in 59% and MDS in 41% of patients. Chromosome abnormalities that frequently involved chromosomes 5, 7 or 11 were documented in 77% of the 189 patients examined. MLL gene rearrangements were detected in 11 of 58 subjects and were correlated with a borderline significance (P = 0.072) with topoisomerase II inhibitor administration. Overall median survival was only 9.7 months. Survival was similar in cases with or without MLL gene rearrangement. Multivariate analysis identified chromosome 5 abnormalities, hypoproteinemia, poor therapy outcomes for primary cancer, C-reactive protein, and thrombocytopenia as being significantly poor prognostic factors (P < 0.05). This large-population study provided a comprehensive update of TRL/MDS status in Japan, identified significant prognostic factors, and enabled the clinical significance of MLL gene rearrangement to be assessed.

Adult↗