A nationwide survey of hypoplastic myelodysplastic syndrome (a multicenter retrospective study).

Hypoplastic myelodysplastic syndrome (hMDS) is a distinct entity with bone marrow (BM) hypocellularity and the risk of death from BM failure (BMF). To elucidate the characteristics of hMDS, the data of 129 patients diagnosed between April 2003 and March 2012 were collected from 20 institutions and the central review team of the National Research Group on Idiopathic Bone Marrow Failure Syndromes, and compared with 115 non-hMDS patients. More RA and fewer CMMoL and RAEB-t in French-American-British (FAB) and more RCUD and MDS-U and fewer RCMD in World Health Organization (WHO) classifications were found in hMDS than non-hMDS with significant differences. The overall survival (OS) and AML progression-free survival (AML-PFS) of hMDS were higher than those of non-hMDS, especially in patients at age ≥50 and of lower risk in Revised International Prognostic Scoring System (IPSS-R). In competing risks analysis, hMDS exhibited decreased risk of AML-progression in lower IPSS or IPSS-R risk patients, and higher risk of death from BMF in patients at age ≥50. Poor performance status (PS ≥2) and high karyotype risks in IPSS-R (high and very high) were significant risk factors of death and AML-progression in Cox proportional hazards analysis.

Refractoriness to platelet transfusion in acute myeloid leukemia correlated with the optical density of anti-platelet factor 4/heparin antibodies.

A small number of reports have described cases of heparin-induced thrombocytopenia complicating hematological disorders with impaired platelet production. We describe the case of a 66-year-old woman with acute myeloid leukemia who exhibited unexplained refractoriness to platelet transfusion, while receiving heparin flushes, and was found to have anti-platelet factor 4 (PF4)/heparin antibodies with high optical density (OD) values (>2 units) detected by an enzyme-linked immunosorbent assay. After cessation of heparin flushes, her refractoriness to platelet transfusion resolved. We retrospectively confirmed that the OD values for anti-PF4/heparin antibodies declined gradually; refractoriness to platelet transfusion resolved when the OD values fell below 1.0 units. Given the absence of any other evident explanation for this phenomenon, and the correlation between the OD values for anti-PF4/heparin antibodies and the efficacy of platelet transfusions, we conclude that the patient's refractoriness to platelet transfusion was most likely caused by anti-PF4/heparin antibodies that had platelet-activating properties.

[Angioimmunoblastic T cell lymphoma complicated with endocapillary proliferative glomerulonephritis].

A 30-year-old female developed fever and multiple lymphadenopathy in September 2011. Her symptoms improved with antibiotic treatment. However, she again presented with fever and multiple lymphadenopathy in December 2011. In addition, she suffered from nephrotic syndrome with severe edema. She was therefore hospitalized to undergo detailed examinations. Renal biopsy revealed endocapillary proliferative glomerulonephritis. Since her renal function deteriorated rapidly, she was given steroid pulse therapy with methylprednisolone, followed by maintenance therapy with prednisolone. After treatment, her renal function improved but multiple lymphadenopathy persisted. Biopsy of a left axillary lymph node was then performed and revealed angioimmunoblastic T-cell lymphoma (AITL). She received CHOP therapy but showed no response. Therefore, she was given ESHAP therapy. A partial response was achieved and the nephrotic syndrome also resolved completely. We report this extremely rare case of renal dysfunction due to endocapillary proliferative glomerulonephritis complicated by AITL.

Prognostic factors and outcomes of unrelated bone marrow transplantation for Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) pre-treated with tyrosine kinase inhibitors.

BACKGROUND: The treatment and prognosis of Acute Lymphoblastic Leukemia (ALL), including Philadelphia chromosome positive ALL (Ph+ALL), a poor prognostic factor, has changed with the introduction of tyrosine kinase inhibitors (TKIs). Nevertheless, allogeneic hematopoietic cell transplantation (allo-HCT) is still recommended as the first-line curative treatment. To date, no study has investigated the prognostic factors and outcomes of unrelated bone marrow transplantation (u-BMT) for Ph+ALL following pre-transplant treatment with a TKI-containing regimen. METHODS: We retrospectively evaluated 15 transplantations of 14 patients with Ph+ALL pre-treated with a TKI-containing regimen at our institute. The 14 patients comprised 11 males and 3 females, with a median age of 50 years (range: 19-64). We performed univariate and multivariate analyses of risk factors that contributed to overall survival (OS) or leukemia-free survival (LFS). RESULTS: Three-year OS of the patients with molecular complete remission (MCR) and with non-MCR at transplantation were 89% and 40% (p = 0.006), respectively, and three-year LFS rates were 79% and 0% (p = 0.001), respectively. Univariate analysis revealed that first hematological complete remission (HCR1) and MCR at transplant were significantly related to better OS and LFS. Multivariate analysis showed that MCR at transplant was significantly associated with better OS and LFS. CONCLUSIONS: In agreement with a previous study that included other stem cell sources, u-BMT was deemed feasible for the treatment of Ph+ALL. Analysis of a larger cohort is required to clarify the prognostic factors that affect transplant outcome in Ph+ALL since the introduction of TKIs.

[Acute transverse myelitis after allogeneic bone marrow transplantation for acute lymphoblastic leukemia--a case report].

Transverse myelitis is an inflammatory disorder of the spinal cord that results in motor, sensory, and autonomic dysfunction. Herein, we describe a 40-year-old Japanese female who developed acute transverse myelitis (ATM) after an unrelated bone marrow transplantation for Philadelphia-positive acute lymphoblastic leukemia in molecular complete remission. Approximately 90 days after transplantation, she suffered from paresthesias, sphincter dysfunction, and lower extremity weakness. Spinal cord magnetic resonance imaging scan demonstrated findings consistent with ATM. The symptoms were resolved with the administration of steroids, followed by intravenous immunoglobulin therapy for a few sequelae. To the best of our knowledge, the presentation of ATM after hematopoietic stem cell transplantation is relatively rare. As the functional prognosis of ATM depends on prompt diagnosis and treatment, we consider that ATM should be included in the differential diagnosis of post-transplant myelopathies.

Prolonged sinus tachycardia caused by human herpesvirus 6 (HHV6) encephalomyelitis after allogeneic bone marrow transplantation.

A 19-year-old man with Philadelphia chromosome-positive acute lymphoblastic leukemia received an allogeneic hematopoietic cell transplant with unrelated bone marrow. On day 20, the patient developed impaired consciousness and disorientation. Examination of the cerebrospinal fluid showed 2×10(4) copies/mL of HHV6B. HHV6 encephalitis was diagnosed, as had HHV6 myelitis based on symptoms that included lancinating pain/pruritus in the lower limbs and dysuria/dyschezia. Concurrently, he showed sinus tachycardia. Even after clearance of the HHV6 genome from the plasma and CSF was achieved by treatment with foscarnet, sinus tachycardia persisted for another 100 days. We suspected prolonged sinus tachycardia due to dysautonomia caused by HHV6 encephalomyelitis.

[Complication of pernicious anemia during interferon-ß treatment for type C chronic hepatitis].

A 62-year-old man with chronic hepatitis C underwent interferon (IFN)-ß therapy. After treatment for a period comprising 29 months and 2 weeks, hematological results showed a decrease in white blood cell, hemoglobin, and platelet counts (WBC 2,300/µl, Hb 7.2 g/dl, PLT 4.7×10(4)/µl), and IFN therapy was stopped. Despite therapy discontinuation, the pancytopenia continued to progress with elevation of LDH (LDH 4,898 IU/l), and the patient was admitted to our hospital with suspected hematological disease. The patient underwent clinical screening, and pernicious anemia caused by vitamin B12 deficiency was diagnosed. The anemia rapidly improved with vitamin B12 treatment. Interferon is the mainstay of treatment for patients with viral hepatitis. While the adverse effects of interferon therapy are widely recognized, only a few reports have documented pernicious anemia developing during IFN-therapy. We recommend that particular attention be paid to such clinical and laboratory conditions as megaloblastic anemia when administering IFN. We also recommend checking the vitamin B12 level, as a deficiency of this vitamin may lead to the development of megaloblastic anemia.

Eosinophilia, regardless of degree, is related to better outcomes after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: Several recent studies report that, after allogeneic hematopoietic cell transplantation (allo-HCT), eosinophilia is a favorable factor for transplant outcomes. However, whether the degree of eosinophilia influences transplant outcomes is yet to be established. METHODS: We studied 144 patients with hematological malignancy who received allo-HCT at our institution. The stem cell sources were bone marrow in 84 patients, peripheral blood stem cells in 32 patients, and cord blood in 28 patients. One hundred and twelve patients underwent myeloablative conditioning and 49 patients had high-risk disease. We performed semi-landmark analysis to examine the influence of eosinophilia. RESULTS: Eosinophilia developed at a median of 47 days after transplantation in 63 patients (44%). The patients with eosinophilia showed significantly better overall survival (OS) and a lower relapse rate at three years, compared to those without eosinophilia (66% vs 55%, p=0.04 and 30% vs 50%, p=0.002). On analysis following division into groups with mild (500-1,500×10(6)/L) and hyper- (>1,500×10(6)/L) eosinophilia, three-year OS and relapse rates were 68% and 65% (p=0.92), and 31% and 28% (p=0.90), respectively. On multivariate analysis, eosinophilia was significantly associated with lower relapse rates [HR: 0.5 (95% CI: 0.3-0.9), p=0.01] and the same trend was preserved in the analysis of the mild and hyper-eosinophilic groups. CONCLUSION: The results suggest that eosinophilia after allo-HCT was associated with better OS and a lower relapse rate, regardless of the levels. The mechanism of this effect is still unclear, and requires study of the pathophysiological process to clarify the relationship between the higher levels of eosinophilia after allo-HCT and organ infiltration.

Different immunoprofiles in patients with chronic myeloid leukemia treated with imatinib, nilotinib or dasatinib.

Immunomodulation induced by dasatinib is reportedly related to better prognosis in chronic myeloid leukemia (CML). However, the underlying mechanism has not yet been fully elucidated. The immunoprofiles of 63 patients in the chronic phase of CML were evaluated during treatment with a tyrosine kinase inhibitor (imatinib, n = 36; nilotinib, n = 9; dasatinib, n = 18). The numbers of CD56 + CD57 + and CD3 + CD57 + cells increased significantly in the dasatinib group. The numbers of regulatory T-cells were comparable among the three groups. Dasatinib markedly enhanced natural killer (NK)-cell reactivity. Only one patient treated with dasatinib showed a slight cytomegalovirus (CMV) reactivation. In contrast, nilotinib suppressed NK-cell reactivity. Plasma levels of interleukin-8 (IL-8), interferon-γ inducible protein-10 (IP-10) and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in all three groups, and plasma levels of granulocyte macrophage-colony stimulating factor (GM-CSF) were significantly elevated in the imatinib and dasatinib groups. Our results suggest the presence of a mechanism for dasatinib-associated immunomodulatory effects that is distinct from CMV reactivation and a decreased number of regulatory T-cells.

[Membranous nephropathy with nephrotic syndrome developed after allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia].

A 38-year-old man was diagnosed with acute lymphoblastic leukemia. We performed myeloablative bone marrow transplantation from an unrelated donor during the patient's first complete remission. After engraftment, he developed acute graft-versus-host disease involving the gastrointestinal tract on day 32. Steroids and mycophenolate mofetil were initiated from day 39. His symptoms improved and the dose of immunosuppressants was tapered and then discontinued on day 421. On day 491, he developed nephrotic syndrome (NS). Based on renal biopsy, membranous nephropathy was diagnosed. There were no apparent symptoms or abnormal laboratory data suggestive of chronic graft-versus-host disease (cGVHD). Steroid therapy was initiated from day 518 and proteinuria improved significantly. NS is very rare following allogeneic hematopoietic stem cell transplantation (allo-HSCT). When there is no concomitant cGVHD, as in this case, allo-HSCT-associated NS is difficult to distinguish from idiopathic NS.

[Chronic myelogenous leukemia complicated by drug-induced agranulocytosis].

We describe a patient with chronic myelogenous leukemia (CML) who developed drug-induced agranulocytosis. A 75-year-old female was diagnosed with CML in December 2001. She had been receiving imatinib therapy for more than five years. In August 2007, she was hospitalized due to a severe neutropenia 10 days after colonoscopy. She was diagnosed as having agranulocytosis induced by colonoscopy premedication including scopolamine butylbromide and flumazenil. Severe neutropenia was resolved by G-CSF treatment without CML progression. Agranulocytosis in patients with CML is rare, but potentially lethal. Here, we report the clinical course in this patient.

Factors that contribute to long-term survival in patients with leukemia not in remission at allogeneic hematopoietic cell transplantation.

BACKGROUND: There has been insufficient examination of the factors affecting long-term survival of more than 5 years in patients with leukemia that is not in remission at transplantation. METHOD: We retrospectively analyzed leukemia not in remission at allogeneic hematopoietic cell transplantation (allo-HCT) performed at our institution between January 1999 and July 2009. Forty-two patients with a median age of 39 years received intensified conditioning (n = 9), standard (n = 12) or reduced-intensity conditioning (n = 21) for allo-HCT. Fourteen patients received individual chemotherapy for cytoreduction during the three weeks prior to reduced-intensity conditioning. Diagnoses comprised acute leukemia (n = 29), chronic myeloid leukemia-accelerated phase (n = 2), myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) (n = 10) and plasma cell leukemia (n = 1). In those with acute leukemia, cytogenetic abnormalities were intermediate (44%) or poor (56%). The median number of blast cells in bone marrow (BM) was 26.0% (range; 0.2-100) before the start of chemotherapy for allo-HCT. Six patients had leukemic involvement of the central nervous system. Stem cell sources were related BM (7%), related peripheral blood (31%), unrelated BM (48%) and unrelated cord blood (CB) (14%). RESULTS: Engraftment was achieved in 33 (79%) of 42 patients. Median time to engraftment was 17 days (range: 9-32). At five years, the cumulative probabilities of acute graft-versus-host disease (GVHD) and chronic GVHD were 63% and 37%, respectively. With a median follow-up of 85 months for surviving patients, the five-year Kaplan-Meier estimates of leukemia-free survival rate and overall survival (OS) were 17% and 19%, respectively. At five years, the cumulative probability of non-relapse mortality was 38%. In the univariable analyses of the influence of pre-transplant variables on OS, poor-risk cytogenetics, number of BM blasts (>26%), MDS overt AML and CB as stem cell source were significantly associated with worse prognosis (p = .03, p = .01, p = .02 and p < .001, respectively). In addition, based on a landmark analysis at 6 months post-transplant, the five-year Kaplan-Meier estimates of OS in patients with and without prior history of chronic GVHD were 64% and 17% (p = .022), respectively. CONCLUSION: Graft-versus-leukemia effects possibly mediated by chronic GVHD may have played a crucial role in long-term survival in, or cure of active leukemia.

Reduced-intensity conditioning by fludarabine/busulfan without additional irradiation or T-cell depletion leads to low non-relapse mortality in unrelated bone marrow transplantation.

In reduced intensity, allogeneic stem cell transplantation from unrelated donors (u-RIST), graft-versus-host disease (GVHD), graft failure, and non-relapse mortality (NRM) are persistent problems. Although anti-thymocyte globulin, alemtuzumab, and total body irradiation (TBI) have been explored as conditioning modalities for u-RIST, the necessity for T-cell depletion or TBI to prevent GVHD or facilitate engraftment in u-RIST has not been determined. We here report the use of u-RIST with bone marrow grafting, following a simple conditioning regimen of 180 mg/m(2) fludarabine and 8 mg/kg of oral or intravenous busulfan without TBI or T-cell depletion. The study population was exclusively Japanese patients with a history of prior chemotherapy. We retrospectively analyzed 31 consecutive patients (median age 53 years). Twenty-five patients (81%) were transplanted from HLA-A, -B, and -DRB1 allele-matched donors. In all patients, neutrophil engraftment was achieved. The cumulative incidence of grade II-IV acute GVHD was 42%. However, 77% of patients with acute GVHD improved with, and could be managed by, initial, systemic, high-dose steroid treatment alone. Two-year overall and event-free survival was 62 and 53%, respectively. The NRM of 10% at 2 years was relatively low. Our results suggest that u-RIST without TBI or T-cell depletion may improve the prognosis after u-RIST in certain patient populations.

Serum cytokine profiles at the onset of severe, diffuse alveolar hemorrhage complicating allogeneic hematopoietic stem cell transplantation, treated successfully with pulse intravenous cyclophosphamide.

A 59-year-old man with lymphoma-type adult T-cell leukemia/lymphoma was admitted to hospital for treatment of a skin relapse on day 398 after allogeneic hematopoietic stem cell transplantation (allo-HSCT). To induce a graft-versus-adult T-cell leukemia/lymphoma effect, we discontinued methylprednisolone and tacrolimus. About a month after the discontinuation, he developed grade II acute graft-versus-host disease (GVHD) with a high fever. Soon after the development of GVHD, all the skin lesions regressed in size and finally vanished. However, he developed diffuse alveolar hemorrhage (DAH), which was resistant to high-dose corticosteroid therapy. He was intubated for respiratory insufficiency on day 451. Cyclophosphamide pulse therapy was administered at a dose of 1 g per day for 2 days and his oxygen saturation then improved, and ventilatory support was released on day 465. On analysis of cytokine profiles at the onset of DAH, we found elevated serum levels of T-helper 2 cytokines as well as T-helper 1 cytokines, suggesting that both T-helper 1 and T-helper 2 cytokines might play a role in the occurrence of DAH following allo-HSCT. Pulse cyclophosphamide treatment might be very effective in suppressing the exaggerated allogeneic immune response in DAH.

[A modified myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation, consisting of intravenous busulfan, cyclophosphamide and total lymphoid irradiation, in advanced leukemia].

In nine patients with advanced acute or chronic leukemia, we performed allogeneic hematopoietic stem cell transplantation (HSCT) following a modified myeloablative conditioning regimen intended to optimize the intensity of conditioning. This regimen consisted of intravenous busulfan 8mg/kg, cyclophosphamide 120mg/kg and total lymphoid irradiation 7.5 Gy. The median age of the patients was 30 years (range 18-59). Stem cell sources were related bone marrow in two, related peripheral blood in one, and unrelated bone marrow in six patients. Prophylaxis against acute graft-versus-host disease (GVHD) was cyclosporine and short-term methotrexate. Acute GVHD appeared in six patients (67%), grade II in all. Extensive chronic GVHD occurred in three of seven evaluable patients. The median follow-up period after HSCT was 813 days (248- 1,702). Of nine patients, five relapsed or progressed after HSCT. However, no patient relapsed or progressed within 100 days after HSCT. During the full follow-up period, transplant-related mortality (TRM) was not observed. The two-year overall survival and event-free survival were 88.9% and 50.0%, respectively. Our results suggested that we might reduce the incidence of TRM and simultaneously control disease by using an optimized conditioning regimen for HSCT.

Heart rate variability during and after peripheral blood stem cell leukapheresis in autologous transplant patients and allogeneic transplant donors.

Side effects of varying severity are frequent in peripheral blood stem cell harvest (PBSCH). Life-threatening complications associated with PBSCH have also been reported. Heart rate variability (HRV), which reflects sympathovagal balance and autonomic cardiovascular control, has been a subject of intense interest in various diseases precipitating sudden death. Here, we prospectively assessed the impact of leukapheresis on HRV among autologous hematopoietic cell transplant patients and healthy donors. We found that HRV indicators, the standard deviation of normal-to-normal intervals (SDNN) value, the square root of the mean of the sum of squared differences between the adjacent normal-to-normal interval (r-MSSD) value, total frequency (TF), high frequency (HF) and low frequency (LF) powers decreased significantly to morbid levels during leukapheresis (all P < 0.01). Morbid changes in SDNN value, TF and LF powers were significantly sustained for 6-9 h after leukapheresis (all P < 0.05). Furthermore, TF and LF powers prior to leukapheresis were significantly lower in subjects with symptomatic hypotension than in the other subjects [3282 (3121-4427) vs. 6018 (4983-9816) ms(2), P = 0.03; 93 (42-144) vs. 237 (142-360) ms(2), P = 0.03, respectively]. Our results suggest that HRV analysis might be of use in evaluating and predicting the adverse effects of cardiovascular complications in PBSCH.

[Epstein-Barr virus-associated post-transplant lymphoproliferative disorder diagnosed by the episode of intestinal perforation following allogeneic hematopoietic stem cell transplantation].

A 64-year-old man was diagnosed as having acute myeloid leukemia. We performed sequential treatment with chemotherapy and reduced-intensity stem cell transplantation from an unrelated donor while the patient was in partial remission. After engraftment, he developed acute graft-versus-host disease of the gut on day 42 and steroid therapy was started. Despite transient aggravation of diarrhea, his symptoms slowly improved and the dose of steroid was tapered. On day 159, he complained of acute left lower abdominal pain. A CT scan showed perforation of the digestive tract and ileectomy was performed. At surgery, multiple ulcers of the intestine were found and one of the ulcers was perforated. Pathologically, transmural and diffuse proliferation of atypical cells in the ulcer were confirmed. Since these cells were positive for CD20 and Epstein-Barr-virus (EBV) encoded RNA, we made a diagnosis of EBV-associated post-transplant lymphoproliferative disorder (PTLD). Reduction in the dose of immunosuppressive agents and rituximab led to complete remission of PTLD. PTLD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is relatively rare, and the development of gastrointestinal perforation after allo-HSCT is very rare.

Impact of relative dose intensity (RDI) in CHOP combined with rituximab (R-CHOP) on survival in diffuse large B-cell lymphoma.

BACKGROUND: Recently, maintaining higher relative dose intensity (RDI) of chemotherapeutic drugs has become a widespread practice in an attempt to achieve better outcomes in the treatment of aggressive lymphoma. The addition of rituximab to chemotherapy regimens has significantly improved outcome in diffuse large B-cell lymphoma (DLBL). However, it is unknown if higher RDI in chemotherapy when combined with rituximab leads to a better outcome in aggressive B-cell lymphoma. METHODS: We retrospectively evaluated the impact of the RDI of initial chemotherapy (consisting of cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) on outcome in 100 newly diagnosed DLBL patients. RESULTS: A multivariate Cox regression model showed that RDI trended towards a significant association with mortality [hazard ratio per 0.1 of RDI = 0.8; 95% confidence interval 0.6-1.0; P = 0.08]. Additionally, on multivariate logistic analysis, advanced age was a significant factor for reduced RDI. CONCLUSION: Our data suggest that in DLBL patients, mortality was affected by RDI of R-CHOP as the initial treatment, and the retention of a high RDI could therefore be crucial.

Efficacy and safety of intravenous itraconazole as empirical antifungal therapy for persistent fever in neutropenic patients with hematological malignancies in Japan.

Recently, empirical antifungal therapy with intravenous itraconazole (ITCZ) for neutropenic patients with antibiotics-resistant fever has been approved by Japanese Ministry of Health, Labour and Welfare on the bases of previous multicenter trials of foreign countries. In this study, we conducted a single-arm, multicenter, prospective study in order to evaluate the efficacy of empirical ITCZ injection on Japanese patients. Sixty-eight patients with hematological diseases who underwent anticancer chemotherapy or stem cell transplantation were enrolled. In this study, we found that the overall clinical response rate to ITCZ injection was 67.6% and success rate of achieving composite endpoints including survival, defervescence during neutropenia, no breakthrough fungal infections, and no premature discontinuation of drug was 50.0%. Mild adverse reactions were observed in 6 patients (8.8%). Further analysis revealed that possible/probable deep fungal infection according to the 2002 and 2008 criteria defined by EORTC/MSG were found in 19.1 and 7.5% of the patients, respectively. Interestingly, response rate to ITCZ injection of possible/probable cases according to the 2002 and 2008 criteria was 61.5% (8/13) and 100% (5/5), respectively. These results not only proved the good efficacy and safety of empirical ITCZ injection for Japanese patients, but also indicated a utility of the drug on future "presumptive" approach.

Cardiac and autonomic nerve function after reduced-intensity stem cell transplantation for hematologic malignancy in patients with pre-transplant cardiac dysfunction.

Recent reports have shown that cardiomyopathy caused by hemochromatosis in severe aplastic anemia is reversible after reduced-intensity allogeneic stem-cell transplantation (RIST). We comprehensively evaluated cardiac and autonomic nerve function to determine whether cardiac dysfunction due to causes other than hemochromatosis is attenuated after RIST. In five patients with cardiac dysfunction before transplant, we analyzed the changes in cardiac and autonomic nerve function after transplant, using electrocardiography (ECG), echocardiography, radionuclide angiography (RNA), serum markers, and heart rate variability (HRV), before and up to 100 days after transplant. There was no significant improvement in cardiac function in any patient and no significant alteration in ECG, echocardiogram, RNA, or serum markers. However, on time-domain analysis of HRV, the SD of normal-to-normal RR intervals (SDNN) and the coefficient of variation of the RR interval (CVRR) decreased significantly 30 and 60 days after transplant (P = 0.04 and 0.01, respectively). Similarly, on frequency-domain analysis of HRV, low and high frequency power (LF and HF) significantly and temporarily decreased (P = 0.003 and 0.03, respectively). Notably, in one patient who had acute heart failure after transplantation, the values of SDNN, CVRR, r-MSSD, LF, and HF at 30 and 60 days after transplantation were the lowest of all the patients. In conclusion, this study suggests that (a) RIST is well-tolerated in patients with cardiac dysfunction, but we cannot expect improvement in cardiac dysfunction due to causes other than hemochromatosis; and (b) monitoring HRV may be useful in predicting cardiac events after RIST.