Nelarabine-induced myelopathy in patients undergoing allogeneic hematopoietic cell transplantation: a report of three cases.

Nelarabine is an effective treatment for T-cell acute lymphoblastic leukemia/lymphoma. Myelopathy is a rare but serious adverse event associated with this drug. Three patients who received nelarabine at the National Cancer Center Hospital from December 2014 to March 2021 developed myelopathy 20 days before, 12 days after, and 29 days after allogeneic hematopoietic cell transplantation (allo-HCT), respectively. Magnetic resonance imaging showed that two of the patients had lesions in the dorsal column or medulla oblongata, and one had no abnormalities in the head or spine. Despite treatment with intravenous immunoglobulin and methylprednisolone, all patients became unable to walk. One patient died on day 101 after allo-HCT due to progressive neurotoxicity. The other two patients showed spontaneous improvement in neurological symptoms, but one died of mucormycosis on day 476. Autopsy revealed spongiosis in the posterior funiculus in both patients who died, and also in the medulla oblongata in one patient. In the surviving patient, positron emission tomography on day 84 showed abnormal accumulation, suggesting continued inflammation. These cases demonstrated pathophysiological features of nelarabine-induced myelopathy and indicate that allo-HCT may worsen the condition. It is necessary to elucidate the underlying mechanism and establish diagnostic methods and therapies.

Rituximab maintenance improves outcomes of transformed diffuse large B-cell lymphoma: a retrospective study of 519 cases with de novo diffuse large B-cell lymphoma and 62 cases with concurrent diffuse large B-cell lymphoma and follicular lymphoma.

Although outcomes of transformed diffuse large B-cell lymphoma (DLBCL) from follicular lymphoma (FL) were improved using rituximab-combined immunochemotherapy, the efficacy of subsequent rituximab maintenance (RM) remains unclear. We retrospectively analyzed the prognoses of 519 patients with de novo DLBCL and 62 patients with concurrent DLBCL and FL (concurrent-DLBCL/FL). Progression-free survival (PFS) was shorter in patients with concurrent-DLBCL/FL than in de novo DLBCL (p=.030). Twenty-four patients with concurrent-DLBCL/FL received RM after induction therapy, and they achieved better OS and PFS (p=.010 and p<.001, respectively) with lower risk of relapse (p<.001) than the non-RM group. Moreover, concurrent-DLBCL/FL showed better subsequent OS and PFS after recurrence than de novo DLBCL (p=.0083 and p=.0044, respectively). Our study indicates that in the face of a high relapse rate, concurrent-DLBCL/FL is manageable and benefits from RM.

Progression-free survival at 24 months as a predictor of survival outcomes after CHOP treatment in patients with peripheral T-cell lymphoma: a single-center validation study in a Japanese population.

Peripheral T-cell lymphoma (PTCL) is a group of aggressive lymphomas commonly treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Progression-free survival at 24 months (PFS24) constitutes a survival predictor for some lymphomas but has not been examined in Asian populations. We retrospectively investigated whether PFS24 was predictive of survival outcomes after CHOP treatment in 73 Japanese patients with PTCL. Patients without PFS24 had shorter median subsequent overall survival (OS) (20.2 vs. 121.0 months, p < 0.001) and shorter median subsequent progression-free survival (5.0 vs. 17.1 months, p = 0.03). Patients without PFS24 had worse overall (62.5% vs. 100%) and complete response rates (45.8% vs. 96.0%) (both p < 0.001). PFS24 absence (hazard ratio: 3.34, p = 0.004) and poor performance status (hazard ratio: 3.17, p = 0.04) were independently predictive of shorter OS. These findings suggest that PFS24 is predictive of survival after CHOP treatment in Japanese patients with PTCL.

The clonal evolution during long-term clinical course of multiple myeloma.

Somatic gene mutations related to acceleration disease and clonal evolution in multiple myeloma strongly influence severe clinical outcomes. In this study, we traced the transition of somatic mutations during the clinical course of myeloma patients over a long-term follow-up period (8.5 year average). Seven myeloma cases treated with immuno-chemotherapy at our institution were analyzed with clinical courses and the results of FISH and G-band analyses. Furthermore, the target sequences in regard to 121 genes, related to driver mutations or acceleration of disease in myeloma, were performed using bone marrow myeloma samples by next-generation sequencing, Ion Proton™ System. We detected a relationship between an increase in the dominant mutated gene (e.g., TP53, DIS3, FAM46C, KDM6B, and EGR1) and poor prognosis. In particular, clonal escalation of the TP53 mutation could not be overcome by any treatment. The selection of a combination treatment conducted in conjunction with the monitoring of gene mutations is appropriate for long-term survival. Our data demonstrate that long-term follow-up of somatic gene mutations during the clinical course of myeloma is helpful in the development of an effective treatment strategy.

Insignificance of surveillance imaging in patients with diffuse large B-cell lymphoma who achieved first complete remission: a retrospective cohort study.

The aim of this study was to evaluate the value of scheduled imaging for patients who achieved first complete remission after CHOP-like chemotherapy plus rituximab. In this retrospective cohort study, we included 759 patients newly diagnosed with de novo diffuse large B-cell lymphoma (DLBCL) at the Cancer Institute, Japanese Foundation for Cancer Research. Relapsed patients were divided into two groups based on method of diagnosis: clinical symptoms (symptom group, n = 57) or scheduled imaging (imaging group, n = 27). Our primary goal was to compare overall survival and relapse-free survival between the two groups. No significant difference in outcomes was found between the symptom and imaging groups. Median overall survival [7.5 years; 95% confidence interval (CI) 4.0-9.7 vs. 9.1 years; 95% CI 2.7 to not reached; P = 0.747), and median relapse-free survival (1.8 years; 95% CI 1.4-2.5 vs. 2.4 years; 95% CI 1.2-4.4; P = 0.108). Surveillance imaging in patients with DLBCL who achieved first complete remission did not demonstrate an advantage in terms of overall survival or relapse-free survival.

The Relationship between Multiple Myeloma with Renal Failure and Metastatic Calcification.

While cases of multiple myeloma (MM) with metastatic calcification have been reported, the mechanisms for this calcification have yet to be explained. We observed a case of MM in a patient with end-stage renal failure who developed vascular and pulmonary calcification. A 51-year-old male was diagnosed with Bence-Jones type MM and required maintenance hemodialysis. He was treated with bortezomib-dexamethasone, vincristine-doxorubicin-dexamethasone, the M2 protocol, and lenalidomide-dexamethasone (Rd) therapy. During the sixth cycle of Rd therapy, he complained of pain in both lower legs. Well-demarcated ulcers with severe pain had developed on the right lower leg, both exterior thighs, and penis. We found that the patient's serum intact parathyroid hormone level was elevated, while it had previously been permissively controlled. Computed tomography scan showed widespread centrilobular opacities of the bilateral lungs and high-density lesions along small blood vessels in the trunk and all four extremities. Histological calcifications were identified in small blood vessels and the alveolar walls. The risk of metastatic calcification in MM appears to be associated with renal failure, but not with MM itself.

[Essential thrombocythemia complicated by intracranial thrombohemorrhagic events].

Although the life expectancy if patients with essential thrombocythemia (ET) is considered to be almost similar to that of the general population, advanced age, leukocytosis, and a previous history of thrombosis are poor prognostic factors, and it is important to prevent thrombohemorrhagic events, leukemic transformation, and secondary malignancies. We report an 85-year-old ET patient with a history of asymptomatic lacunar infarction, who developed symptomatic cerebral infarction and even chronic subdural hematoma. It is necessary to follow patients who have asymptomatic cerebral infarction or chronic ischemic change and to examine the necessity of brain imaging and treatment intervention at the time of diagnosis.

Acute undifferentiated leukemia (stem cell acute leukemia) showing differentiation to Langerhans cell-like cells in lymph nodes.

A 75-year-old woman was referred to our hospital with suspected leukemia. Complete blood count demonstrated WBC 3,810/µl with 26% blasts, Hb of 11.7 g/dl and Plt of 18.0×104/µl. Bone marrow aspiration revealed blasts (86.3%) with expressions of CD34, CD7, TdT, CD33, and CD117. MPO was negative. Chromosomal analysis of the bone marrow showed isolated trisomy 10 in all leukemic cells (20/20). Swelling of superficial lymph nodes was also observed. Cervical lymph node biopsy revealed leukemic blasts which had the same phenotype as those in the bone marrow except that proliferation of Langerhans cell-like cells (LCs) was observed in the paracortex. LCs had pale cytoplasm and grooved nuclei, and were positive for both CD1a and S100 protein. Trisomy 10 was detected in both the leukemic blasts and the LCs by fluorescence in situ hybridization. This rare case strongly suggests leukemic cells to differentiate into LCs.

Experience of Peripherally Inserted Central Venous Catheter in Patients with Hematologic Diseases.

Objective Although use of the peripherally inserted central venous catheter (PICC) has become increasingly common, there are few reports of PICCs used for patients with hematologic diseases. In this study, we analyzed the safety of PICC placement in patients with hematologic diseases where PICCs had been placed to perform blood collection, blood transfusion, drug administration, and hematopoietic stem cell transplantation. Methods This study included 142 PICCs placed in 95 patients managed at our department from November 2013 to December 2015. The PICCs used were the Groshong® Catheter (NXT single-lumen; BARD Inc.). Results A total of 95 patients underwent the placement of 142 PICCs. The mean patient age was 65.5 years. The total duration of catheterization was 8,089 days, with a mean duration of 57.0 days. Chemotherapy was administered through 107 catheters. Stem cells were injected through 12 catheters. Although a fever was observed in association with 103 catheters, it was generally controlled by antimicrobial therapy. There were 18 catheter-related bloodstream infection (CRBSI) cases, an incidence equivalent to 2.1 cases per 1,000 catheter-days. Conclusion The present study demonstrated a low CRBSI incidence rate and found no evidence of serious complications with PICC placement. PICCs can be used for blood collection, blood transfusion, drug administration, and hematopoietic stem cell transplantation without problems. Thus, PICC placement appears to be a safe procedure for patients with hematologic diseases. Safe catheters are therefore urgently needed for these patients. We expect that PICCs will be widely adopted in Japan in the near future.