Prognostic factors in patients in the terminal phase of haematological malignancies who are receiving home medical care.

Although there are many prognostic models for patients in the terminal phase of solid tumours, a reliable prognostic scoring system in patients in the terminal phase of haematological malignancies (HM) has not been established. We retrospectively evaluated 180 patients in the terminal phase of HM who were receiving home medical care (HMC). Multivariate analyses revealed that clinician's estimate, consciousness, loss of appetite, dyspnoea, neutrophil count, lymphocyte count, and lactate dehydrogenase were associated with overall survival (OS). Based on this result, we developed a novel prognostic scoring system, the Japan palliative haematological oncology prognostic estimates, in which four risk groups were shown to clearly differ in survival (p < 0.001): a low-risk group (n = 41, median OS of 434 days), an intermediate-low-risk group (n = 80, median OS of 112 days), an intermediate-high-risk group (n = 38, median OS of 31.5 days), and a high-risk group (n = 21, median OS of 10 days). This is the first investigation of prognostic factors that influence the OS of patients in the terminal phase of HM who are receiving HMC. Providing patients with reliable information about their prognosis is important for them to consider how to spend their remaining life.

Granulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case report.

BACKGROUND: Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential inhibitory regulator of immune activation. CTLA-4 haploinsufficiency is known to be associated with dysregulation of FOXP3+ regulatory T cells, hyperactivation of effector T cells, and lymphocytic infiltration of multiple organs. However, there have only been a few reports of renal involvement with CTLA-4. Herein, we present a case of acute granulomatous tubulointerstitial nephritis (TIN) in a patient with CTLA-4 haploinsufficiency. CASE PRESENTATION: A 44-year-old man presented with a 3-week history of fever and malaise, and subsequently developed acute kidney injury (AKI) a few days after treatment with levofloxacin (LVFX). A kidney biopsy and immunohistochemical staining revealed granulomatous TIN with dominantly infiltrating CD4+ T cells. General symptoms and renal impairment showed improvement after discontinuation of LVFX and initiation of oral steroids. However, they worsened following steroid tapering. Further, a colon biopsy analysis showed similar findings to the renal tissue analysis. We suspected that granulomatous TIN was possibly associated with CTLA-4 haploinsufficiency. Therefore, the patient was transferred to another hospital for further treatment of CTLA-4 haploinsufficiency using immunosuppressive agents. CONCLUSIONS: There have been few reports regarding renal involvement of CTLA-4 haploinsufficiency. In the present case, granulomatous TIN could have arisen due to instability of immune regulatory functions, such as CTLA-4 haploinsufficiency, and treatment with LVFX could have triggered immunologic activation and severe inflammation as well as renal dysfunction.

[Haploidentical stem cell transplantation for acute myeloid leukemia associated with adult-onset Shwachman-Diamond syndrome].

A 21-year-old man presented with bone marrow failure, short stature, fatty degeneration of the pancreas on CT images, and Shwachman-Bodian-Diamond syndrome (SBDS) gene abnormalities (exon 2: c.258+2T>C and deletion of exon 3). Thus, the patient was diagnosed with Shwachman-Diamond syndrome (SDS). In the clinical course, the patient developed acute myeloid leukemia (AML). Hematopoietic stem cell transplantation from the human-leukocytic-antigen-haploidentical father of the patient was performed. The patient was conditioned with 150 mg/m2 fludarabine, 6.4 mg/kg busulfan, and 4 Gy total body irradiation. Graft-versus-host disease prophylaxis included tacrolimus, micophenolate mofetil, and posttransplant cyclophosphamide. Although the patient achieved a complete remission on day 21, AML relapsed on day 434 after the transplantation. He died of sepsis. The prognosis of patients with SDS and AML is poor. Adult-onset cases must be recognized, and transplantation should be performed during bone marrow failure.

[Acquired hemophilia complicated with hemorrhage induced acute renal failure].

A 63-year-old woman, without a family history of hemophilia, was admitted to our hospital because of subcutaneous bleeding, intramuscular and intra-articular hematoma, and macroscopic hematuria. On routine blood analysis, a prolonged activated partial thromboplastin time, decreased concentration of factor VIII to less than 1%, and a markedly elevated level of factor VIII inhibitor to 14.1 BU/ml were revealed. Diagnosis of acquired hemophilia was made and she was treated with prednisolone and recombinant activated factor VII (rFVIIa). On day 9 of rFVIIa therapy, she was complicated by acute renal failure (ARF) with increasing macroscopic hematuria. Computed tomography revealed bilateral swelling of the kidneys with bleeding and dilatation of the left renal pelvis. Activated prothrombin complex concentrates (aPCC) was administrated in combination with steroid pulse therapy and hydration. The bleeding tendency, including ARF, was improved with aPCC, and she was treated with prednisolone and cyclophosphamide. She is currently in good health and attending an outpatients' clinic. Acquired hemophilia is associated with various underlying conditions, but our patient did not show any previous history. ARF is a rare complication in acquired hemophilia, requiring a non-invasive treatment combination with early induction of immunosuppressive therapy.

Close relation between 14q32/IGH translocations and chromosome 13 abnormalities in multiple myeloma: a high incidence of 11q13/CCND1 and 16q23/MAF.

Many B-cell tumors have chromosomal translocations that result from failures of the immunoglobulin (Ig) gene during V(D)J recombination, somatic hypermutation (SHM), and class switch recombination (CSR). Nearly half of all multiple myeloma (MM) patients have 14q32/IGH translocations in CSR, including the five common translocations of 11q13/CCND1, 6p21/CCND3, 4p16/FGFR3, 16q23/MAF, and 20q11/MAFB. Although 14q32/IGH translocations are closely related to the biological features of MM, the most consistent and powerful prognostic factor has been reported to be the loss of all (monosomy 13/-13) or part of chromosome 13 (del(13)(q14)/13q-). Our fluorescence in situ hybridization (FISH) analysis method was designed to detect -13/13q- and 14q32/IGH rearrangements in 23 MM patients. FISH disclosed 14q32/IGH translocations in 10 of the 23 (43.5%) patients. The common translocation partners of 14q32/IGH were 11q13/CCND1 (five patients) and 16q23/MAF (four patients), followed in third place by 4p16/FGFR3 (one patient). Nine of the ten patients carrying 14q32/IGH translocations had -13/13q-. Abnormalities of chromosome 13 included -13 in seven (70%) and del(13)(q14) in two (20%). Our results suggest a significant correlation between the presence of 14q32/IGH translocations and chromosome 13 abnormalities (P = 0.0276) in MM patients.