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Naoto Tomita, Hirotaka Takasaki,
Kazuho Miyashita,
Shin Fujisawa,
Eriko Ogusa,
Shiro Matsuura,
Kumiko Kishimoto,
Ayumi Numata,
Atsuko Fujita,
Rika Ohshima,
Hideyuki Kuwabara,
Maki Hagihara,
Chizuko Hashimoto,
Sachiya Takemura,
Hideyuki Koharazawa,
Etsuko Yamazaki,
Katsumichi Fujimaki,
Jun Taguchi,
Rika Sakai,
Yoshiaki Ishigatsubo
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ABSTRACT: Long-term observation has identified a pattern of continuing relapse in limited stage diffuse large B-cell lymphoma (DLBCL) treated by three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) plus involved-field irradiation. We retrospectively analysed 190 untreated patients with limited stage DLBCL treated by R-CHOP alone. All the patients were scheduled to undergo primary therapy with six cycles of full-dose R-CHOP. Cases with a dose reduction of more than 20% were excluded from the study. Additional local irradiation was allowed in patients with partial response (PR). Five patients received additional local irradiation after PR at the end of the R-CHOP therapy. The median observation period was 52 months. Median age at diagnosis was 63 years. The responses to therapy were 180 complete responses, eight PR, and two progression of disease (PD). The 5-year progression-free survival and 5-year overall survival rates were 84% and 90%, respectively, both in plateau. During the observation period, 29 patients experienced PD. The progression sites were the primary sites in 15 patients, outside the primary sites in 10, and undetermined in four patients. These results suggest that the 'standard' strategy of three cycles of R-CHOP followed by involved-field radiotherapy for limited stage DLBCL could be effectively replaced by six cycles of R-CHOP alone.
British Journal of Haematology 02/2013; · 4.94 Impact Factor
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ABSTRACT: High-dose chemotherapy with autologous stem cell transplant is commonly used for diffuse large B-cell lymphoma that recurs after successful salvage chemotherapy. However, in patients in whom the disease recurs again, the prognosis is poor. A 40-year-old woman who underwent allogeneic stem cell transplant 4 years after autologous stem cell transplant developed recurrent diffuse large B-cell lymphoma 3 years after the initial autologous stem cell transplant. She then underwent reduced-intensity hematopoietic stem cell transplant from a human leukocyte antigen-matched, unrelated donor who was not the previous autologous stem cell transplant donor. She achieved a long survival (328 days after the reduced-intensity hematopoietic stem cell transplant and 1844 days after the first allogeneic transplant). A second allogenic transplant may provide survival benefits in a proportion of patients with malignant lymphoma recurring after allogeneic transplant, although careful consideration is required because of the high risk of treatment-related mortality with second allogenic transplant.
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 02/2013;
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Wataru Yamamoto,
Naoya Nakamura,
Naoto Tomita,
Yoshimi Ishii, Hirotaka Takasaki,
Chizuko Hashimoto,
Shigeki Motomura,
Etsuko Yamazaki,
Rika Ohshima,
Ayumi Numata,
Yoshiaki Ishigatsubo,
Rika Sakai
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ABSTRACT: Abstract Primary mediastinal (thymic) large B-cell lymphoma (PMLBCL) and nodular sclerosis classical Hodgkin lymphoma (NSCHL) are the major histological types of lymphoma affecting the mediastinum. We reviewed 27 patients with PMLBCL and 14 patients with NSCHL. A poor performance status, high serum lactate dehydrogenase level, and strong positivity for PAX5 were all significantly more common in patients with PMLBCL than in those with NSCHL. Severe fibrosis was frequent in NSCHL, but not in PMLBCL. PDL1 was expressed by 11/25 PMLBCLs (44.0%) versus 1/9 NSCHLs (11.1%). Expression of BCL6 was significantly more frequent in PDL1-positive PMLBCL than in PDL1-negative PMLBCL, but there were no clinical differences between these two groups. Two PMLBCL patients with a poor prognosis had CD20(-), CD79a(+), CD15(-), and CD30(-), possibly representing a subtype of mediastinal grey zone lymphoma.
Leukemia & lymphoma 09/2012; · 2.40 Impact Factor
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Shoichi Kobayashi,
Risa Kumagai,
Akiko Omiya,
Hideki Tanno,
Yoshimi Ishii,
Wataru Yamamoto, Hirotaka Takasaki,
Rika Sakai,
Ayumi Numata,
Kenji Matsumoto,
Masatsugu Tanaka,
Heiwa Kanamori,
Shigeki Motomura,
Atsuo Maruta
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ABSTRACT: We studied immunophenotypic analysis of hematogones by flow cytometry. A total of 102 specimens from 93 patients with acute leukemia (52 specimens), myelodysplastic syndromes (4), or malignant lymphoma (46) were analyzed between April and August, 2011. Hematogones were detected in 55 specimens and highly identified in patients with acute myeloid leukemia in remission and B cell lymphoma. Stage 1 (CD34(+)CD20(-)) and stage 2/3 (CD34(-)CD20(+)) were detected in 9.9% and 52.7%, respectively. In addition, the intermediate type (CD34(+)CD20(+)) was identified in 37.4%. All specimens of stage 3 in bright CD45 expression were positive for CD5 and included CD5(+)CD23(-)CD11c(-), 11.1%, CD5(+)CD23(+)CD11c(-), 85.2%, and CD5(+)CD23(+)CD11c(+), 3.7%. These findings suggest that hematogones with unreported immunophenotypes may exist and the appearance of hematogones in hematologic malignancies may be relatively frequent.
[Rinshō ketsueki] The Japanese journal of clinical hematology 08/2012; 53(8):753-9.
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ABSTRACT: A 40-year-old Japanese man with acute myeloid leukemia received allogeneic bone marrow transplantation. On day 101, varicella-zoster virus (VZV) infection occurred, but was improved by administration of acyclovir and immunoglobulin. On day 119, he complained of numbness and double vision, and he was admitted due to exacerbation of the symptoms. The findings of cerebrospinal fluid and magnetic resonance image examination were consistent with the diagnosis of immune-mediated encephalomyelitis (IMEM). Intravenous immunoglobulin therapy was effective and his neurological findings dramatically improved without recurrence. IMEM is a rare non-infectious inflammatory demyelinating disease that can occur after transplantation. We herein describe a case report with a review of the associated literature.
[Rinshō ketsueki] The Japanese journal of clinical hematology 04/2012; 53(4):465-8.
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Hirotaka Takasaki,
Masatsugu Tanaka,
Takayoshi Tachibana,
Ayumi Numata,
Katsumichi Fujimaki,
Rika Sakai,
Shin Fujisawa,
Naoto Tomita,
Hiroyuki Fujita,
Atsuo Maruta,
Yoshiaki Ishigatsubo,
Heiwa Kanamori
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ABSTRACT: We retrospectively analyzed patients aged C 50 years with hematologic malignancies who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) to identify preoperative variables predicting the outcome. There were 71 patients with a median age of 57 years (range: 50-63 years) who had acute leukemia (n = 53) or myelodysplastic syndrome (n = 18). Myeloablative conditioning was done in 35 patients and 36 patients had reduced-intensity conditioning. The 5-year overall survival rate (OS), cumulative relapse rate, and non-relapse mortality rate (NRM) were 45, 24, and 33%, respectively. According to multivariate analysis, high-risk disease (HR 3.50, 95% CI 1.43-8.56, P = 0.006), a hematopoietic cell transplantation comorbidity index (HCT-CI) score ≥ 3 (HR 4.41, 95% CI 1.31-14.77, P = 0.016), and an HLA-mismatched unrelated donor (HR 4.03, 95% CI 1.46-11.10, P = 0.007) were significant predictors of worse OS. Highrisk disease was also significantly associated with a higher cumulative relapse rate (HR 4.59, 95% CI 0.94-6.92, P = 0.065). Furthermore, an HCT-CI score ≥ 3 (HR 3.02, 95% CI 1.01-20.78, P = 0.048) and an HLA-mismatched unrelated donor (HR 3.02, 95% CI 1.04-8.74, P = 0.042) were risk factors for NRM. These results suggest that the disease risk, HCT-CI score, and donor type/histocompatibility are prognostic factors for elderly patients, while the conditioning regimen and age are not predictors.
International journal of hematology 02/2012; 95(3):291-8. · 1.17 Impact Factor
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ABSTRACT: We newly diagnosed 131 patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue lymphoma between 1998 and 2010. We retrospectively studied 124 patients for whom complete clinical data were available at presentation and who had minimally undergone tumour staging by physical examination, computed tomography (CT), bone marrow aspiration, and biopsy. A slight female predominance (men, 58; women, 66) was observed in the study population; the median age was 67 years. The primary locations at presentation were the stomach (38%), orbita (20%), lung (12%), intestinal tract (8%), thyroid gland (6%), others (14%), and unknown (2%). Seventy per cent of patients had localized disease. Of the 124 patients, 14 (11%) had lymph node involvement, and 5 (4%) had bone marrow involvement. Five (4%) patients had both lung and gastric involvement. The 5-year overall survival rate for the 124 patients was 96.1%. The overall vital prognosis was excellent. Moreover, gastro-intestinal fiberscopic examination is essential, especially in cases with lung involvement at presentation. Copyright © 2012 John Wiley & Sons, Ltd.
Hematological Oncology 01/2012; · 2.47 Impact Factor
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ABSTRACT: We retrospectively analysed 16 cases of newly diagnosed pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma in the Japanese population. The disease was found on the basis of examination findings in 14 cases, and clinical manifestations in 2. According to the extensive staging procedure, four patients had concomitant gastric involvement. Primary treatment involved surgery alone in two patients; surgery followed by rituximab (R)-containing chemotherapy in two; R-containing chemotherapy alone in 11; and chemoradiotherapy without R in one. Over the median observation period of 28 months, disease progression was recorded in three patients, but all 16 patients were alive at the end of the observation period. One patient was treated with R alone and achieved partial remission; subsequent tentative surgery showed no evidence of residual lymphoma. It has been 72 months of progression-free survival after the diagnosis. Primary pulmonary MALT lymphoma exhibited an indolent clinical course. R has potential as a therapeutic agent in patients with pulmonary MALT lymphoma. Copyright © 2012 John Wiley & Sons, Ltd.
Hematological Oncology 01/2012; · 2.47 Impact Factor
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ABSTRACT: The impact of lymphocyte subpopulations on the outcome of bone marrow transplantation (BMT) remains uncertain. We investigated the relationship between the lymphocyte subpopulations of bone marrow grafts and the outcome of BMT. A total of 121 patients who underwent BMT at Kanagawa Cancer Center between 2000 and 2009 were analyzed. Grade III-IV acute graft-versus-host disease (GVHD) occurred in 35.9% of patients who received unrelated BMT with a CD56 cell dose ≤2.80×10(6)/kg versus only 9.7% of patients with a CD56 cell dose >2.80×10(6)/kg (P=0.017). In patients receiving related BMT, the cumulative incidence of grade III-IV acute GVHD did not differ significantly in relation to the CD56 cell dose. On multivariate analysis, older donor age (hazard ratio (HR): 1.09, 95% confidence interval (CI): 1.03-1.15, P=0.004) and a high dose of CD56 cells (>2.80×10(6)/kg) (HR: 0.15, 95%CI: 0.03-0.92, P=0.040) were significant determinants of grade III-IV acute GVHD after unrelated BMT. None of the lymphocyte subpopulations had a significant impact on the outcome of transplantation, including the rate of neutrophil engraftment, relapse, relapse-free mortality, and overall survival. Our findings suggest that a high natural killer cell dose prevents severe acute GVHD after unrelated BMT, while sparing the graft-versus-leukemia effect.
Leukemia research 12/2011; 36(6):699-703. · 2.36 Impact Factor
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International journal of hematology 12/2011; 94(6):580-2. · 1.17 Impact Factor
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Takayoshi Tachibana,
Masatsugu Tanaka,
Ayumi Numata, Hirotaka Takasaki,
Satomi Ito,
Rika Ohshima,
Maki Hagihara,
Etsuko Yamazaki,
Naoto Tomita,
Katsumichi Fujimaki,
Jun Taguchi,
Rika Sakai,
Hiroyuki Fujita,
Shin Fujisawa,
Atsuo Maruta,
Yoshiaki Ishigatsubo,
Heiwa Kanamori
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ABSTRACT: A multicenter retrospective analysis of the influence of pretransplant serum ferritin (SF) was performed in 261 adult recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT), including 159 patients with acute myeloid leukemia (AML), 66 with acute lymphoid leukemia (ALL) and 36 with myelodysplastic syndrome (MDS). Patients were divided into subgroups according to the pretransplant SF level [< 1000 ng/mL (low) vs. ≥ 1000 ng/mL (high)] and disease status at transplant. A high SF level was significantly associated with high disease risk (p = 0.041), but pretransplant SF and disease risk were independent significant prognostic factors for overall survival (OS), disease-free survival (DFS) and non-relapse mortality rate (NRM) on multivariate analysis. The high-SF group showed a worse outcome than the low-SF group among both standard-risk patients (OS: 54% vs. 64%, p = 0.043; DFS: 46% vs. 57%, p = 0.031) and high-risk patients (OS: 16% vs. 35%, p = 0.001; DFS: 15% vs. 34%, p = 0.001). In conclusion, a high SF at transplant adversely influences the outcome of allo-HSCT regardless of disease risk in patients with acute leukemia and MDS.
Leukemia & lymphoma 09/2011; 53(3):456-61. · 2.40 Impact Factor
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Katsuhiro Miura, Hirotaka Takasaki,
Hideki Tsujimura,
Masatoshi Kanno,
Yoshinobu Maeda,
Naoto Tomita,
Kazue Takai,
Yasufumi Masaki,
Jun Takizawa,
Hiraku Mori,
Yasushi Terasaki,
Takashi Yoshida,
Jin Takeuchi,
Shigeki Motomura
International journal of hematology 05/2011; 93(5):684-6. · 1.17 Impact Factor
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Takayoshi Tachibana,
Masatsugu Tanaka, Hirotaka Takasaki,
Ayumi Numata,
Satomi Ito,
Reina Watanabe,
Rie Hyo,
Rika Ohshima,
Maki Hagihara,
Rika Sakai,
Shin Fujisawa,
Naoto Tomita,
Hiroyuki Fujita,
Atsuo Maruta,
Yoshiaki Ishigatsubo,
Heiwa Kanamori
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ABSTRACT: We retrospectively studied the association between iron overload and bloodstream infections (BSI) in the 100-day period following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia or myelodysplastic syndromes. Serum ferritin was measured before transplantation to evaluate iron overload. Of 114 adult patients who underwent transplantation between 2000 and 2008, 36 (32%) developed BSI. Of the 44 isolates, 63% were Gram-positive bacteria, 32% were Gram-negative bacteria, and 4% were fungi. The median time to the onset of the first BSI was day 28 (range day 0-95) after transplantation. Univariate analysis revealed a significantly higher incidence of BSI in the high (≥ 1,000 ng/ml, n = 57) than in the low (< 1,000 ng/ml, n = 57) ferritin group (42.1 versus 21.1%, respectively, P = 0.017). Peripheral blood stem cell transplantation (PBSCT) (n = 23) showed a greater protective effect against BSI compared with bone marrow (n = 71) and cord blood (n = 20) transplantation. Pretransplantation serum ferritin (HR = 2.844, 95% CI: 1.180-6.859, P = 0.020) and PBSCT (HR = 0.135, 95% CI: 0.025-0.717, P = 0.019) were significant factors on multivariate analysis. In conclusion, pretransplantation serum ferritin significantly predicts BSI within the 100-day period after allo-HSCT.
International journal of hematology 02/2011; 93(3):368-74. · 1.17 Impact Factor
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ABSTRACT: Bevacizumab (BV) is widely used for patients with metastatic colorectal cancer. We investigated the efficacy and safety of chemotherapy combined with BV for metastatic colorectal cancer. From July 2007 to October 2008, 59 patients were treated by chemotherapy with BV in our hospital. Of the 47 patients who received BV in first-line therapy, 3 cases (6%) with complete response (CR), 25 cases(53%) with partial response (PR), and 17 cases (36%) with stable disease (SD) were observed. The overall response rate and tumor control rate were 60% and 96%, respectively. The median progression-free survival (PFS) was 11. 9 months, and median overall survival (OS) was 23. 6 months. There were 12 patients treated first with BV in second-line therapy. Of the 12 patients, 1 case (8%) with CR, 3 cases (25%) with PR, and 4 (33%) with SD were observed. The overall response rate and tumor control rate were 33% and 67%, respectively. The median PFS was 6.0 months and median OS was not reached. With regard to the grade 3 to 4 adverse events by NCI-CTCAE ver3.0, neutropenia was observed in more than half of the patients (56%), but a few of patients had gastrointestinal toxicities, peripheral neuropathy and infections in non-hematologic toxicities. BV-associated adverse events were hypertension, proteinuria, venous thrombosis, wound healing complication, gastrointestinal perforation and bleeding, each of which were few and not serious. Six of the patients experienced PD after first-line therapy treated with BV continuously in second-line therapy. Four of six were surviving without disease progression at the last follow-up, which suggests the effectiveness of continuation of BV. Our study showed the efficacy and safety of BV for metastatic colorectal cancer.
Gan to kagaku ryoho. Cancer & chemotherapy 01/2011; 38(1):79-83.
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ABSTRACT: A 68-year-old man was admitted to our hospital in September 2008 because of a left-sided chest pain. Bone marrow examination showed that 85.5% of leukemic cells were positive for myeloperoxidase (MPO) and were negative for esterase stain. Flow cytometric analysis (FCM) revealed the expression of CD19, CD79a, CD13, CD33, CD34, and HLA-DR on the blasts. Cytogenetic analysis of bone marrow cells using the G-banding technique demonstrated 47, XY, +X, t(4;11;7)(q21;q23;q22) in five of the 20 analyzed cells. The patient was diagnosed as having mixed biphenotypic acute leukemia according to the European Group for Immunologic Classification of Leukemia criteria. Mixed-phenotype acute leukemia is a rare, difficult to diagnose entity. Whether patients with mixed-phenotype acute leukemia should be treated with regimens designed for acute myeloid leukemia, acute lymphoblastic leukemia, or both remains unclear.
Case reports in hematology. 01/2011; 2011:148482.
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Rika Ohshima,
Shigeki Motomura,
Chizuko Hashimoto,
Takuya Miyazaki,
Satomi Ito, Hirotaka Takasaki,
Rie Hyo,
Hideyuki Koharazawa,
Sachiya Takemura,
Etsuko Yamazaki,
Katsumichi Fujimaki,
Naoto Tomita,
Hiroyuki Fujita,
Shin Fujisawa,
Hiroshi Harano,
Heiwa Kanamori,
Yoshiaki Ishigatsubo
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ABSTRACT: Fifty-eight newly diagnosed patients with Hodgkin lymphoma were treated with ABVD chemotherapy at Yokohama City University Hematology group from October 1996 to June 2005. The median age of patients age was 41 years old and ranged from 15 to 75. Thirty-eight patients were in the early stage and 20 patients were in the advanced stage. Patients in the early stage received 3 cycles of ABVD chemotherapy and involved-field radiation therapy, while those in the advanced stage received 6 cycles of ABVD chemotherapy. The overall response rate in patients was 100% (CR 87%, PR 13%) in the early stage and 95% in the advanced stage. With a median follow-up of 44 months, the 3-year progression-free survival and overall survival were 89% and 95% in the early stage, and 70% and 81% in the advanced stage, respectively. The results of this study were similar to those previously reported in Western countries.
[Rinshō ketsueki] The Japanese journal of clinical hematology 12/2010; 51(12):1756-61.
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ABSTRACT: Sequential high-dose chemotherapy with in vivo rituximab-purged stem cell autografting was designed for previously untreated mantle cell lymphoma (MCL). The response rate, disease-free survival (DFS), overall survival (OS) and toxicity were investigated in this trial. Between November 2001 and August 2008, five patients younger than 65 years of age with MCL at diagnosis were enrolled in this study. Initial chemotherapy consisted of 3 cycles of CHOP regimen followed by four courses of high-dose chemotherapy. During the in vivo purging phase, the patient was administered high-dose cyclophosphamide and cytarabine, and then each administration was followed by two infusions of rituximab. Molecular monitoring of minimal residual disease was performed by assessing DNA samples from bone marrow and autografted cells using PCR amplification of the bcl-1/IgH rearrangement. The complete response rate was 100%, and the 3-year OS and DFS were 100% and 100%, respectively. PCR analysis of autografted cells from four evaluable patients, 75% lymphoma-negative harvests were achieved following in vivo purging. One patient relapsed 3.2 years after treatment. The principal toxicity in the study was hematologic but there were no treatment-related deaths. Intensive high-dose sequential chemotherapy with in vivo purged stem cell support can achieve long-term disease-free survival for MCL.
[Rinshō ketsueki] The Japanese journal of clinical hematology 01/2010; 51(1):57-62.
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International journal of hematology 01/2010; 91(1):154-6. · 1.17 Impact Factor
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Katsumichi Fujimaki,
Masatsugu Tanaka, Hirotaka Takasaki,
Rie Hyo,
Tomoko Kawano,
Rika Sakai,
Hiroyuki Fujita,
Shin Fujisawa,
Heiwa Kanamori,
Atsuo Maruta,
Yoshiaki Ishigatsubo
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ABSTRACT: To reduce the relapse rate for hematological malignancies after allogeneic hematopoietic stem cell transplantation, we employed a myeloablative regimen comprising thiotepa 400 mg/m(2), cyclophosphamide 3,600 mg/m(2) and total body irradiation 10 Gy. Materials and
Subjects comprised 17 patients (median age, 53 years; range, 50-56 years) with hematological malignancies who received allogeneic hematopoietic stem cell transplantation from HLA-identical related (n=6), HLA-mismatched family (n=2) or unrelated donors (n=9). Prophylaxis of acute graft-versus-host disease (GVHD) consisted of short-term methotrexate and cyclosporine (n=4) or short-term methotrexate and tacrolimus (n=13).
No grade IV regimen-related toxicities as determined by Bearman's criteria were encountered. Acute grade II-IV GVHD developed in 7 patients, with chronic GVHD in 11 patients. With a median follow-up of 39 months, 3 years survival rate after transplantation was 59%. Two patients died due to infection by 100 days after transplantation. Only 1 patient with Philadelphia-positive acute lymphoblastic leukemia experienced relapse. Eight patients died of non-leukemic causes (sepsis, n=2; liver dysfunction, n=2; idiopathic interstitial pneumonia, n=1; bacterial pneumonia, n=1; bronchiolitis obliterans resulting from chronic GVHD, n=1; and disseminated infection with varicella zoster virus, n=1).
This regimen was tolerable, but a large trial is warranted to confirm the efficacy of this conditioning.
Internal Medicine 02/2008; 47(5):379-83. · 0.94 Impact Factor
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ABSTRACT: It has been reported in the Western literature that patients with chronic renal disease have developed anti-erythropoietin (EPO) antibody-related pure red cell aplasia (PRCA). To investigate the incidence of anti-EPO antibody-related PRCA in Japan, we designed a questionnaire survey based on previous reports of patients who had PRCA during treatment with EPO. Thirteen of 17 patients were evaluated in this study. In all 13 patients, EPO delivery was via injection, 9 subcutaneously, 2 intravenously and 2 with a combination of the 2 methods. Three of 4 patients treated with subcutaneous EPO administration were positive for anti-EPO antibodies, but all patients treated by intravenous injection were negative. The EPO was stopped in 8 patients after the onset of PRCA, and immunosuppressive therapy with prednisolone and/or cyclosporine was administered in 12 patients. An improvement in PRCA was obtained in 12 patients. It was suspected that previous reports in Japan may have included both anti-EPO antibody-associated PRCA and incidental cases. Furthermore, subcutaneous administration of EPO may effect the production of anti-EPO antibodies.
[Rinshō ketsueki] The Japanese journal of clinical hematology 06/2007; 48(5):391-6.
