Refractory viremia/viral disease is a major life-threatening complication that may arise among patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). This study aimed to clarify the therapeutic effect of high-dose polyclonal intravenous immunoglobulin (IVIG) against viremia/viral diseases after allo-HCT. We conducted a pilot study to investigate the therapeutic effect of 400 mg/kg of IVIG given for 5 consecutive days against refractory viremia/viral disease after allo-HCT. Overall, 7 patients were drug-resistant and the other 7 had not previously received any drug for their viremia/viral disease. All patients completed the 5-day therapy regimen of IVIG. A complete response at Day 56 was observed for 8 of 14 patients (57.1%). Additionally, 10 of 14 patients (71.4%) were alive at Day 56, although only one death occurred due to the viremia/viral disease. Remarkably, all 3 cases who developed exogenous viremia/viral diseases including respiratory syncytial virus pneumonia/bronchitis and human parvovirus B19 viremia achieved a complete response, suggesting that high-dose polyclonal IVIG may be more effective against exogenous viruses rather than endogenous ones. Congestive heart failure was observed in 1 patient. High-dose polyclonal IVIG could be an effective and feasible therapy for refractory viremia/viral disease after allo-HCT.
A 56-year-old man diagnosed with multiple myeloma was treated with CBD (cyclophosphamide, bortezomib, and dexamethasone; DEX), which was discontinued because of bortezomib-associated adverse events. Thereafter, he was treated with Ld (lenalidomide; LEN+DEX) followed by high-dose chemotherapy with autologous stem cell rescue, resulting in a complete response. Ld as maintenance therapy was discontinued because of immune thrombocytopenia, resulting in disease progression. Although treatment was switched to Pd (pomalidomide+DEX), DLd (daratumumab+LEN+DEX), and IRd (ixazomib+LEN+DEX); the patient's M protein level continued to increase and the extramedullary disease expanded despite radiotherapy. He was treated with E-Ld (elotuzumab+LEN+DEX) after 3 cycles of short VAD (vincristine, doxorubicin, and DEX). The extramedullary disease disappeared after 8 cycles of E-Ld. To the best of our knowledge, this is the first report showing the effectiveness of E-Ld treatment for extramedullary disease of a heavily treated patient for multiple myeloma. We believe that the clinical course of this patient provides useful insights about the antimyeloma mechanism of elotuzumab.
Development of acute myeloid leukemia (AML) during pregnancy is rare, and the available data are limited to small retrospective reports. Currently, no guidelines exist for the management of AML during pregnancy in Japan. A 26-year-old female was diagnosed with AML at 19 weeks of gestation, received chemotherapy with daunorubicin and cytarabine, and achieved complete remission. Following the first consolidation therapy, she gave birth to a 1964-g female infant by cesarean section at 33 weeks of gestation. One week later, she was initiated on the second consolidation therapy; however, she developed a pelvic abscess during neutropenia. She underwent urgent surgery for open drainage and recovered soon after surgery. She has been in complete remission for eight months, and the daughter is healthy. Chemotherapy delivered after the second trimester rarely causes congenital malformations and may not require the termination of pregnancy. The clinical course of the present case suggests that chemotherapy can be performed safely and effectively in pregnant patients with AML after the trimester and babies.
A 81-year-old female was diagnosed with symptomatic multiple myeloma (MM; IgG κ type, D&S: IIB, ISS: 2) in August 2017. Although treatment with lenalidomide and dexamethasone was started, she developed deep venous thrombosis in the lower extremities as a complication; therefore, the treatment was changed to DBd. In February 2018, she required hospitalization due to general weakness and altered consciousness. Her IgG level and κ/λ ratio were elevated at 4,156 mg/dl and 605.56, respectively, revealing that MM was treatment-resistant. A protein-cell dissociation (cell blood count, 0/µl; protein, 100.6 mg/dl) was detected in the cerebrospinal fluid, whereas the ammonia level in serum was high (172 µg/dl). T2-weighted magnetic resonance imaging showed a broad range of high-density area in deep cerebral white matter suggesting leukoencephalopathy, whereas the cerebrospinal fluid was negative for JC virus. No pathological conditions causing secondary hyperammonemia were found. Although the involvement of drug-induced leukoencephalopathy in altered consciousness could not be ruled out since the chromosome with the normal karyotype at the first visit had a complex chromosomal abnormality, an originally minor clone of MM cells with a chromosomal abnormality might have contributed to the ammonia production resulting in altered consciousness.
A 78-year-old man was hospitalized because of rapid progression of chronic renal failure and diagnosed with multiple myeloma (MM) IgG-λ type ISS-III R-ISS-II with complex karyotype including t(14;19). Even after receiving bortezomib-based regimens, his renal failure progressed. He became dependent on dialysis, which was required three times a week. After introducing the daratumumab (DARA)-based regimen, his renal function improved, the frequency of dialysis decreased to twice a week, and the free light chain (FLC) ratio also improved. However, his myeloma eventually followed a refractory course; therefore, pomalidomide (POM)-dexamethasone (Pd) regimen was administered. Pd regimen had a marked effect and normalized the FLC ratio after three courses of the treatment. However, his myeloma reprogressed with multiple extramedullary masses and he became del(17p) positive; eventually, he died on the 470th day of disease. MM with t(14;19) is rare and has a poor prognosis with a highly aggressive course; however, early introduction of DARA or POM may provide long-term response.
Nodal marginal zone lymphoma (NMZL) is a form of nodal B-cell lymphoma exhibiting proliferation of abnormal lymphocytes at the circumference of the mantle zone in the lymph nodes. Although the outcome of patients with this disease is often favorable, we recently encountered a patient with a CD5-positive NMZL who was resistant to chemotherapy. A 67-year-old woman complaining of systemic lymph node swelling was referred to our hospital. After biopsy of the neck lymph node, she was diagnosed with CD5-positive NMZL. Disease progression was revealed after 16 months, and she was initially treated with chemotherapy consisting of rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP). However, this therapy was ineffective. Subsequent therapy with rituximab and bendamustine also failed to induce remission. A rebiopsy revealed that the NMZL had transformed into a diffuse large B-cell lymphoma. This patient died after 2 years from the initial diagnosis due to lymphoma progression. Cases of CD5-positive NMZL are rare; thus, it is difficult to study the clinical implications of CD5 expression in this disease. Here we describe the current understanding of CD5 expression in NMZL.
Richter syndrome (RS) is the development of an aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL). Most cases of diffuse large B-cell lymphoma variant of RS are clonally related to the original CLL. Here, we present a case of mantle cell lymphoma (MCL) that developed sequentially during the clinical course of CLL. A 72-year-old man had been diagnosed with CLL 16 years ago and was followed-up without treatment. He developed autoimmune hemolytic anemia 2 years ago, which resolved with rituximab and prednisolone treatment. Subsequently, he presented with fever, abdominal bloating, and fatigue. Progressive lymphocytosis and splenomegaly with elevated lactic dehydrogenase levels were suggestive of RS. Bone marrow examination revealed a small- to medium-sized lymphoid infiltrate, which was positive for CD5, CD20, CCND1, and SOX-11 and negative for CD23 and LEF1 on immunostaining. Fluorescence in situ hybridization analysis was positive for IgH/CCND1, which indicated MCL. Southern blot analysis showed that both the MCL and the previous CLL expressed different IgH gene rearrangement bands. At the time of relapse or progression of CLL, sequential development of MCL should be considered.
A 54-year-old man with acute myeloid leukemia (AML) underwent allogeneic bone marrow transplantation from a human leukocyte antigen-matched unrelated donor in nonremission status. Bone marrow aspiration performed on day 14 showed that the patient had achieved complete remission; however, he relapsed on day 28. The patient developed a wet cough, and chest computed tomography performed on day 27 revealed pneumonia. Because pneumonia developed along with the leukemic relapse, we suspected that it was due to pulmonary leukemic infiltration (PLI). Giemsa-stained sputum showed some blast cells and fluorescence in situ hybridization indicated that the patient had monosomy 7, which was also detected in bone marrow blasts. Though we prescribed hydroxycarbamide and decreased tacrolimus rapidly, AML progressed and led to the patient's death on day 45. Histopathological findings of the autopsy performed the next day showed diffuse alveolar damage in both lungs. The blast cells were packed in blood vessels of alveolar septa and were also seen in alveoli. PLI was diagnosed pathologically. In conclusion, our case demonstrates that Giemsa stain of sputum is useful in quick diagnosis of PLI without invasive examination.
A 70-year-old woman experienced pain in both gastrocnemius muscles, numbness in the toes, and muscle weakness in both the legs that lasted for two months. After getting admitted to our hospital, the muscle weakness extended to both her arms, and nerve conduction studies revealed decreased nerve conduction velocity, which was more prominent in the elbow and the axilla than in the wrist. A magnetic resonance imaging revealed a tumor in the right femoral neck, which was histologically diagnosed as plasmacytoma. Laboratory findings revealed IgA lambda type M protein and an elevated VEGF level of 2,320 pg/ml; edema was present in both the legs. After a diagnosis of POEMS syndrome, lenalidomide and dexamethasone treatment were initiated simultaneously, along with irradiation. The treatment improved polyneuropathy, along with a decrease in the VEGF level. Increased vascular permeability due to elevated VEGF led to the development of neuropathy of POEMS syndrome, and treatment against proliferating monoclonal plasma cells is effective. In the present case, we believe that a prompt control of the plasmacytoma with novel therapeutic agents for myeloma with irradiation resulted in the improvement of the neurological symptoms.
This report presents the case of a 68-year-old female patient previously diagnosed with thymoma by her local doctor. She was referred to our hospital for surgery, and the thymoma was removed and diagnosed as a World Health Organization (WHO) classification type AB thymoma. After surgery, she experienced general malaise, a loss of appetite, and weight loss, so she visited our hospital in May 2019. A blood test showed hypogammaglobulinemia and low B lymphocytes. A bone marrow examination revealed no morphological abnormalities. Flow cytometric analysis indicated a marked decrease in both the B cell-related surface markers CD19 and CD20 and the T cell-related surface marker CD4, and the CD4/CD8 ratio was also low. She was diagnosed with Good’s syndrome, and immunoglobulin replacement therapy was administered. She subsequently developed hemophagocytic lymphohistiocytosis (HLH) due to infection and was treated according to the HLH2004 protocol, but she finally succumbed to multiple organ damage as a result of sepsis. Given that Good’s syndrome is associated with both humoral and cellular immune dysfunctions, affected patients tend to develop severe infections and have a poor prognosis. In such cases, early detection, regular immunoglobulin replacement therapy, and infection prevention therapies are important.
A 46-year-old female patient underwent a cord blood transplantation (conditioning regimen: fludarabine/busulfan4/melphalan80; graft-versus-host disease (GVHD) prophylaxis: tacrolimus + mycophenolate mofetil) for acute myeloid leukemia (AML) with her 1st hematological complete response to induction therapy (idarubicin 3 days+cytarabine 7 days). She lost her consciousness due to human herpesvirus 6 (HHV-6) encephalitis on day 31, and therefore, we increased the foscarnet dosage (from 120 mg/kg to 180 mg/kg). Her consciousness level improved after treatment. However, 8 hours of sudden hypothermia occurred with hyperhidrosis, hypertension, and subsequent hyperglycemia on day 34. Her condition did not improve even after administration of anticonvulsant, steroid pulse, or intravenous immunoglobulin. A total of 75 attacks were observed until she was discharged on day 471. She has not shown chronic GVHD or relapsed AML since then. However, HHV-6 caused prolonged damage to her hypothalamus as observed through magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) using 99mTc ethyl cysteinate dimer even when the virus was not detected from her cerebrospinal fluid. This damage can be responsible for the hypothermia attacks. This is the first case report of prolonged series of hypothermia attacks for over a year as a sequela of HHV-6 encephalitis after a cord blood transplantation for AML.
A fulfilling communication between healthcare professionals and patients is important during medical interviews, especially when asking sex-life-related questions in compliance with TERMS® (Thalidomide Education and Risk Management System) and RevMate® (procedures for proper management of Revlimid® (lenalidomide) and Pomalyst® (pomalidomide)). Educational systems for improving medical communications related to sexual issues remain to be developed. Therefore, we surveyed real views of healthcare professionals and patients involved in thalidomide treatment. We created an educational DVD and a side reader to improve medical communications under the aid from Japan Agency for Medical Research and Development (AMED).