Single-Center Study of 72 Patients with Severe Combined Immunodeficiency: Clinical and Laboratory Features and Outcomes

Journal of Clinical Immunology - Severe combined immunodeficiency is an inborn error of immunity characterized by impairments in the numbers and functions of T and B lymphocytes due to various...     

Novel Mutation in <Emphasis Type="Italic">CECR1</Emphasis> Leads to Deficiency of ADA2 with Associated Neutropenia

Purpose

Adenosine deaminase 2 (ADA2) have been reported to cause vasculitic diseases and immunodeficiency recently. Patients present with stroke episodes and rashes mimicking polyarteritis nodosa (PAN). We report a patient who has been followed up with severe neutropenia and found an unexpectedly revealed novel mutation in CECR1 affecting ADA2.

Methods

We reviewed medical records and clinical history of the patient. No mutations in other known neutropenia genes such as ELA, G6PC3, HAX1, AP3B1, LAMTOR2, VPS13B, VPS45, GFI1, JAGN1, or WAS could be detected. Sanger sequencing was used to confirm the genetic variants in the patient and relatives.

Results

Genetic analysis by exome sequencing revealed a novel mutation in the gene CECR1 (c.G962A; p.G321E) which segregated perfectly in the relatives.

Conclusion

This is the first DADA2 patient presenting with severe neutropenia. We suggest that in patients with unexplained cytopenias combined with immunodeficiency, fevers of unknown origin and high inflammation markers, DADA2 should be considered.

     

HLA-haploidentical transplantations for primary immunodeficiencies: a single-center experience

SCID is characterized by profound deficiencies of T and B lymphocytes. HSCT is the only curative treatment for children with SCID. The clinical characteristics and outcome of 30 HLA-haploidentical transplantations in 18 patients (15 SCID, two Omenn syndrome, and one MHC Class II deficiency) are reported here. The age of patients at diagnosis ranged from one and half to nine months (median: four months). The median time was one month between the diagnosis and the time of the initial transplantation. Infused CD34+ stem cell dose was ranged between 7 and 94.2 × 10(6) /kg. Nine of 18 patients were found to be positive for CMV antigenemia at diagnosis; therefore, none of them received a conditioning regimen. The most common complication was graft failure (61%), so repeated transplantations (two to four) were performed in seven patients. The mean time of lymphoid engraftment was 17.5 days (median: 16, range: 11-29 days). Ten of 15 SCID (67%) patients survived with a stable complete donor chimerism. However, all three non-SCID patients died. In conclusion, in the absence of a matched family donor, HLA-haploidentical transplantation from parental donors represents a readily available treatment option especially for patients with SCID, offering a high chance of cure.     

Clinically Positive Axillary Lymphadenopathy May Lead to False Diagnosis of Overstaged Breast Cancer in Patients with Sjögren's Syndrome: A Case Report

Sj?gren's syndrome (SS) is an autoimmune disease that chronic inflammation and lymph node proliferation. Patients with SS carry a greater risk of developing lymphoproliferative malignancy. In addition to other organ cancers, breast cancer may also occur in these patients. Considering these, breast cancer in patients with SS can be misdiagnosed as being in an advanced stage particularly in the presence of axillary lymphadenopathy. Here, we report a rare case of a 45-year-old woman with SS who presented with a breast mass. Radiology showed a 4 cm solid lesion and conglomerates of axillary lymphadonepathy. A breast biopsy revealed ductal carcinoma in situ. A modified radical mastectomy was performed; however, no axillary metastases were detected. Clinicians should remain vigilant to the possibility that a false clinical impression of axillary metastasis may occur in such patients with breast cancer. Therefore, axillary node status should be verified first.     

Neoadjuvant chronomodulated capecitabine with radiotherapy in rectal cancer: a phase II brunch regimen study

Purpose

The aim of this study was to evaluate efficacy and safety of chronomodulated capecitabine administered according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer.

Methods

Eighty-five patients with stage II and III rectal cancer were included. Patients received capecitabine (1,650 mg/m² per day; 60 % dose at 8:00 AM and 40 % dose at 12:00 noon) administered during pelvic radiation (total 50.4 Gy in 28 fractions, 1.8 Gy daily dose between 2:00 p.m. and 4:00 p.m.). After chemoradiotherapy, patients underwent surgery. The primary endpoints were pathological complete response (pCR) rate and toxicity.

Results

In 17 patients (20 %), total tumor regression was achieved according to Dworak pathological grading system. Grade III diarrhea occurred in nine patients (10.5 %), while only one patient had grade 3 thrombocytopenia. Grade II or III proctitis were seen in nine (10.5 %) subjects, and grade I or II cystitis in six (6.9 %). Only three patients (3.3 %) developed hand and foot syndrome (both grade I–II). There were no grade IV toxicities.

Conclusions

Brunch Regimen for locally advanced rectal cancer consisting of neoadjuvant chronomodulated capecitabine and concurrent radiation therapy is effective and well tolerated with good safety profile, particularly with regard to the occurrence of hand and foot syndrome, in patients with locally advanced rectal cancer.     

Pure laparoscopic versus open live donor nephrectomy: evaluation of health survey and graft functions

Background

Laparoscopic donor nephrectomy (LDN) has become the gold standard in many kidney transplantation centers seeking to increase the number of potential live donors. This study was designed to compare the health surveys and graft functions between LDN and open donor nephrectomy (ODN).

Methods

We retrospectively analyzed all patients who underwent donor nephrectomy between December 2005 and September 2009 who had at least 1 year of follow-up. We reviewed demographic data, operative time, warm ischemia period, graft function, and quality of life.

Results

Among the 132 cases, 98 were pure LDN and 34 were ODN. Demographic data were similar in both groups. Operative times were significantly longer in the ODN group but warm ischemia times significantly longer in the LDN group. However, graft functions were similar in both groups. There was 1 graft loss due to arterial thrombosis of the transplanted kidney among the LDN group. Short-Form 36 health survey scores were similar except for the role-physical subscale.

Conclusion

Although we failed to observe a significant difference between ODN and LDN as far as the quality of life and graft functions were concerned, the previously documented advantages of laparoscopy with similar operative results suggest? LDN to be the gold standard for this procedure in our institution.     

Single stapler technique in laparoscopic donor nephrectomy

Background

Laparoscopic donor nephrectomy (LDN) is usually performed with at least 2 separate vascular staplers for division of the renal artery and vein. However, we used a single stapler regardless of the number of renal arteries and veins. Furthermore, the graft was quickly retrieved by hand without using an extraction bag using our technique. Herein we have presented our experience with LDN of grafts with single or multiple renal arteries and/or veins using a single stapler and hand removal.

Methods

We reviewed demographic data, operative and warm ischemia times, postoperative complications, and graft function.

Results

Between December 2005 and September 2009, we performed 85 cases with 1 renal artery (group LDN-1), 8 cases with two renal arteries (group LDN-2), and 5 cases with 3 or more renal arteries (group LDN-3). The demographic data among the groups were similar. The mean operative time was significantly longer among groups LDN-2 (100.3 ± 9.5 minutes) and LDN-3 (120.6 ± 10.3 minutes) compared with LDN-1 (76.1 ± 9.3 minutes; P < .001). Similar results were observed with respect to warm ischemia times. There were no significant differences related to graft function and outcomes among these groups.

Conclusion

The single stapler and hand removal technique was safe, technically feasible, and cost effective regardless of the number of renal arteries and veins. This technique removes the necessity of additional staplers and extraction bags, lowers the operative and warm ischemia times, and thus decreases the cost.