Treatment of severe neutropenia with high-dose pyridoxine in a patient with chronic graft versus host disease and squamous cell carcinoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>The differential diagnosis of neutropenia includes medications, infections, autoimmune diseases, and deficiencies of Vitamin B12 and folate. The association of Vitamin B6 deficiency with severe neutropenia is a rare finding.</p> <p>Case presentation</p> <p>A 51-year-old Caucasian woman presented with fever and profound neutropenia (48 neutrophils/uL). Her clinical history included non-Hodgkin lymphoma, in remission following treatment with allogeneic bone marrow transplantation, quiescent chronic graft-versus-host disease, and squamous cell carcinoma of the skin metastatic to cervical lymph nodes. Medications included atenolol, topical clobetasol, Ditropan (oxybutynin), prophylactic voriconazole, prophylactic valganciclovir, Soriatane (acitretin), and Carac (fluorouracil) cream. The bone marrow was hypocellular without metastatic cancer or myelodysplasia. Neutropenia did not respond to stopping medications that have been associated with neutropenia (valganciclovir, voriconazole and Soriatane) or treatment with antibiotics or granulocyte colony stimulating factor. Blood tests revealed absence of antineutrophil antibodies, normal folate and B12 levels, moderate zinc deficiency and severe Vitamin B6 deficiency. Replacement therapy with oral Vitamin B6 restored blood vitamin levels to the normal range and corrected the neutropenia. Her cervical adenopathy regressed clinically and became negative on scintography following Vitamin B6 therapy and normalization of the blood neutrophil count.</p> <p>Conclusion</p> <p>Severe pyridoxine deficiency can lead to neutropenia. Screening for Vitamin B6 deficiency, along with folate and Vitamin B12 levels, is recommended in patients with refractory neutropenia, especially those with possible malabsorption syndromes, or a history of chronic-graft-versus host disease. Severe neutropenia may facilitate progression of squamous cell carcinoma.</p

Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR

Background: In the phase III CASTOR study in relapsed or refractory multiple myeloma, daratumumab, bortezomib, and dexamethasone (D-Vd) demonstrated significant clinical benefit versus Vd alone. Outcomes after 40.0 months of median follow-up are discussed. Patients and Methods: Eligible patients had received ≥ 1 line of treatment and were administered bortezomib (1.3 mg/m2) and dexamethasone (20 mg) for 8 cycles with or without daratumumab (16 mg/kg) until disease progression. Results: Of 498 patients in the intent-to-treat (ITT) population (D-Vd, n = 251; Vd, n = 247), 47% had 1 prior line of treatment (1PL; D-Vd, n = 122; Vd, n = 113). Median progression-free survival (PFS) was significantly prolonged with D-Vd versus Vd in the ITT population (16.7 vs. 7.1 months; hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.25-0.40; P < .0001) and the 1PL subgroup (27.0 vs. 7.9 months; HR, 0.22; 95% CI, 0.15-0.32; P < .0001). In lenalidomide-refractory patients, the median PFS was 7.8 versus 4.9 months (HR, 0.44; 95% CI, 0.28-0.68; P = .0002) for D-Vd (n = 60) versus Vd (n = 81). Minimal residual disease (MRD)–negativity rates (10−5) were greater with D-Vd versus Vd (ITT: 14% vs. 2%; 1PL: 20% vs. 3%; both P < .0001). PFS2 was significantly prolonged with D-Vd versus Vd (ITT: HR, 0.48; 95% CI, 0.38-0.61; 1PL: HR, 0.35; 95% CI, 0.24-0.51; P < .0001). No new safety concerns were observed. Conclusion: After 3 years, D-Vd maintained significant benefits in patients with relapsed or refractory multiple myeloma with a consistent safety profile. D-Vd provided the greatest benefit at first relapse and increased MRD-negativity rates.CASTOR showed the significant clinical benefit of daratumumab plus bortezomib and dexamethasone for patients with previously treated multiple myeloma. With ∼3 years median follow-up, this regimen continues to demonstrate significantly improved progression-free survival with higher minimal residual dis

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci

Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma (MM)

From Single Nucleotide Polymorphisms to Constant Immunosuppression: Mesenchymal Stem Cell Therapy for Autoimmune Diseases

The regenerative abilities and the immunosuppressive properties of mesenchymal stromal cells (MSCs) make them potentially the ideal cellular product of choice for treatment of autoimmune and other immune mediated disorders. Although the usefulness of MSCs for therapeutic applications is in early phases, their potential clinical use remains of great interest. Current clinical evidence of use of MSCs from both autologous and allogeneic sources to treat autoimmune disorders confers conflicting clinical benefit outcomes. These varied results may possibly be due to MSC use across wide range of autoimmune disorders with clinical heterogeneity or due to variability of the cellular product. In the light of recent genome wide association studies (GWAS), linking predisposition of autoimmune diseases to single nucleotide polymorphisms (SNPs) in the susceptible genetic loci, the clinical relevance of MSCs possessing SNPs in the critical effector molecules of immunosuppression is largely undiscussed. It is of further interest in the allogeneic setting, where SNPs in the target pathway of MSC's intervention may also modulate clinical outcome. In the present review, we have discussed the known critical SNPs predisposing to disease susceptibility in various autoimmune diseases and their significance in the immunomodulatory properties of MSCs