Secondary hypogammaglobulinemia in adults—A large retrospective cohort study / Hipogammaglobulinemia secundaria en adultos: estudio de cohorte retrospectiva

Background and objective: IgG replacement therapy (IgG-RT) has radically changed the clinical evolution of primary immunodeficiencies, yet the information regarding secondary hypogammaglobulinemia (SHG) is insufficient or conflicting. We aim to describe clinical features, evolution and treatment of SHG patients in our center. Methods: Dynamic retrospective cohort between January 2001 and July 2021 of adults with gamma globulin fraction <0.6g/dL in a serum protein electrophoresis and a coincident decrease of IgG levels – with a disease-related SHG or treatment that reduces serum immunoglobulins. Results: We included 1012 patients with SHG with a median follow-up of 5 years (IQR 2–8). Hematological diseases were identified in 95% of the patients and 61% received drugs related to SHG. Sixty five percent had more than one etiological factor associated with SHG. Infectious diseases were present in 69% of the patients, 48% had respiratory infections and 17% had severe infections. There was statistical association between respiratory and severe infections with multiple myeloma (MM), lymphoma and rituximab. MGUS had less infections and death compared with other etiologies. IgG-RT was indicated in 18.7% of the patients and 4.6% received it for more than 6 months with variable intervals. Among the latter group, there was a significant reduction of all-type infections and respiratory infections with IgG-RT (p<0.001), and it was consistent with similar findings in lymphoma, MM and all IgG levels subgroups. Conclusion: SHG was associated with more than one etiological factor and a high frequency of infections. IgG-RT indication was irregular yet still effective. It is relevant to consider IgG levels screening, monitoring and accurate indication of IgG-RT.(AU)

Antecedentes y objetivos: La IgG sustitutiva ha cambiado radicalmente la evolución de las inmunodeficiencias primarias, mientras que la información sobre hipogammaglobulinemia secundaria (HGS) es insuficiente y discordante. El objetivo del estudio es describir las características clínicas, evolución y tratamiento de pacientes con HGS. Métodos: Cohorte retrospectiva dinámica entre enero de 2001 y julio de 2021 de adultos con proteinograma y fracción de gammaglobulina <0,6g/dL y dosaje disminuido de IgG, con enfermedad o tratamiento que produzcan HGS. Resultados: Se incluyó a 1.012 pacientes con HGS con una mediana de seguimiento de 5 años (IIC 2-8). El 95% tenía enfermedad hematológica y el 61% recibió fármacos asociados a HGS. El 65% tenía más de un factor etiológico asociado con HGS. El 69% presentó infecciones de cualquier tipo, el 48% infecciones respiratorias y el 17%, infecciones graves. Hubo asociación significativa entre infecciones respiratorias y graves entre los subgrupos de mieloma múltiple, linfoma y rituximab. Los pacientes con MGUS tuvieron menor frecuencia de infecciones y muerte comparados con otros factores etiológicos. El 18,7% de los pacientes recibió IgG sustitutiva y el 4,6% de forma crónica, con intervalos variables. Los últimos tuvieron disminución significativa de infecciones de cualquier tipo e infecciones respiratorias con IgG sustitutiva (p<0,001), que se mantuvo en los subgrupos con mieloma múltiple, linfoma y todos los niveles de IgG. Conclusión: La HGS asoció más de un factor etiológico y alta frecuencia de infecciones. La indicación de IgG sustitutiva fue irregular, pero, aún así, efectiva. Se plantea considerar el dosaje de inmunoglobulinas, monitoreo y la adecuada indicación de IgG sustitutiva.(AU)

Association of Laparoscopic Approach With Improved Short-Term Outcomes in Patients With Hematologic Malignancy Undergoing Splenectomy.

BACKGROUND: Patients with hematologic malignancies undergo splenectomy for both diagnostic and therapeutic purposes. Although minimally invasive surgery continues to be increasingly utilized for a variety of abdominal operations, no large-scale data has compared the postoperative outcomes for laparoscopic vs open splenectomy in patients with hematologic malignancy. METHODS: Patients with a diagnosis of hematologic malignancy who underwent laparoscopic and open splenectomy between 2015 and 2020 were queried using the ACS-NSQIP database. 30-day outcomes of laparoscopic vs open splenectomy were compared. RESULTS: Out of 430 patients included in the study, 52.6% were male, with a mean age of 63.4 ± 13.1 years. 233 patients (54.2%) underwent laparoscopic splenectomy. On bivariate analysis, laparoscopic surgery was associated with lower rates of 30-day mortality [2.1% vs 11.7% (P < .001)] and morbidity [9.0% vs 24.4% (P < .001)]. On multivariate regression, elective operations (OR .255, 95%CI: 0.084-.778, P = .016) and laparoscopic surgery (OR .239, 95%CI: 0.075-.760, P = .015) were independently associated with lower mortality, while history of metastatic cancer (OR 3.331, 95%CI: 1.144-9.699, P = .027) was associated with higher mortality. Laparoscopic surgery (OR .401, 95%CI: 0.209-.770, P = .006) and steroid use (OR 2.714, 95%CI: 1.279-5.757, P = .009) were the only two factors independently associated with 30-day morbidity. Laparoscopic surgery was also associated with shorter hospital length of stay (median 3 [IQR:3] vs 6 [IQR:7] days). CONCLUSION: Laparoscopic splenectomy was associated with lower 30-day mortality and morbidity, and shorter length of stay in patients with hematologic malignancies. These data suggest that laparoscopic approach, when feasible, may be preferred for splenectomy in this patient population.

Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis.

BACKGROUND: In patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT), a calcineurin inhibitor plus methotrexate has been a standard prophylaxis against graft-versus-host disease (GVHD). A phase 2 study indicated the potential superiority of a post-transplantation regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil. METHODS: In a phase 3 trial, we randomly assigned adults with hematologic cancers in a 1:1 ratio to receive cyclophosphamide-tacrolimus-mycophenolate mofetil (experimental prophylaxis) or tacrolimus-methotrexate (standard prophylaxis). The patients underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched (i.e., mismatched at only one of the HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci) unrelated donor, after reduced-intensity conditioning. The primary end point was GVHD-free, relapse-free survival at 1 year, assessed in a time-to-event analysis, with events defined as grade III or IV acute GVHD, chronic GVHD warranting systemic immunosuppression, disease relapse or progression, and death from any cause. RESULTS: In a multivariate Cox regression analysis, GVHD-free, relapse-free survival was significantly more common among the 214 patients in the experimental-prophylaxis group than among the 217 patients in the standard-prophylaxis group (hazard ratio for grade III or IV acute GVHD, chronic GVHD, disease relapse or progression, or death, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P = 0.001). At 1 year, the adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) with experimental prophylaxis and 34.9% (95% CI, 28.6 to 41.3) with standard prophylaxis. Patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall and disease-free survival, relapse, transplantation-related death, and engraftment did not differ substantially between the groups. CONCLUSIONS: Among patients undergoing allogeneic HLA-matched HSCT with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly more common among those who received cyclophosphamide-tacrolimus-mycophenolate mofetil than among those who received tacrolimus-methotrexate. (Funded by the National Heart, Lung, and Blood Institute and others; BMT CTN 1703 ClinicalTrials.gov number, NCT03959241.).

Cholecystectomy in patients with hematologic malignancies.

BACKGROUND: Cholecystectomy in patients with hematologic malignancies remains poorly understood. METHODS: We retrospectively evaluated patients with hematologic malignancies who underwent cholecystectomy at a single institution. RESULTS: Of 313 patients who presented for evaluation of abdominal pain, 64 underwent cholecystectomy for acute cholecystitis (34.4%), gangrenous cholecystitis (21.9%), chronic cholecystitis (23.4%), and cholelithiasis (20%). Most had a history of hematopoietic cell transplantation (62.5%) and/or immunosuppressive medication within 30 days of consultation (82.8%). Ultrasound had a 39% false-negative rate for acute nongangrenous cholecystitis. Operative time was 92 ± 39 min, 7 were performed open, 10 had intraoperative transfusions, and 4 had grade 3+ complications. Intraoperative transfusion was associated with increased postoperative length of stay (p = 0.03). Open procedure, operative time, estimated blood loss, intraoperative transfusion, and complications were not associated with timing of surgery. CONCLUSIONS: Patients with hematologic malignancies can safely undergo cholecystectomy. Length of postoperative stay for inpatients is associated with intraoperative blood transfusion.

Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies.

PURPOSE: Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD). METHODS: This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or severe) or relapse-free survival (CRFS). RESULTS: Among 346 patients enrolled, 327 received HCT, 300 per protocol. Intent-to-treat rates of 2-year CRFS were 50.6% for CD34 selection (hazard ratio [HR] compared with control, 0.80; 95% CI, 0.56 to 1.15; P = .24), 48.1% for PTCy (HR, 0.86; 0.61 to 1.23; P = .41), and 41.0% for control. Corresponding rates of overall survival were 60.1% (HR, 1.74; 1.09 to 2.80; P = .02), 76.2% (HR, 1.02; 0.60 to 1.72; P = .95), and 76.1%. CD34 selection was associated with lower moderate to severe cGVHD (HR, 0.25; 0.12 to 0.52; P = .02) but higher transplant-related mortality (HR, 2.76; 1.26 to 6.06; P = .01). PTCy was associated with comparable cGVHD and survival outcomes to control, and a trend toward lower disease relapse (HR, 0.52; 0.28 to 0.96; P = .037). CONCLUSION: CNI-free interventions as performed herein did not result in superior CRFS compared with tacrolimus and methotrexate with BM. Lower rates of moderate and severe cGVHD did not translate into improved survival.

Low Soluble Programmed Cell Death Protein 1 Levels After Allogeneic Stem Cell Transplantation Predict Moderate or Severe Chronic GvHD and Inferior Overall Survival.

Programmed cell death protein-1 (PD-1) is an inhibitory co-receptor required for regulating immune responsiveness and maintaining immune homeostasis. As PD-1 can be released as bioactive soluble molecule, we investigated the clinical significance of soluble PD-1 (sPD-1) after allogeneic hematopoietic stem cell transplantation (HSCT) regarding graft-versus-host disease (GvHD), relapse, and overall survival (OS) in a mono-centric cohort of 82 patients. Compared to pre-HSCT and to healthy controls, post-HSCT sPD-1 plasma levels were significantly increased during an observation time of three months. Univariate analysis revealed that low sPD-1 plasma levels at month one, two or three post HSCT were associated with acute GvHD grade III-IV, the onset of moderate/severe chronic GvHD (cGvHD) and inferior OS, DFS, and TRM, respectively. No relationship was detected to relapse rates. sPD-1 plasma levels were significantly increased in ATG-treated patients compared to ATG-untreated patients. Multivariate analysis revealed that a low sPD-1 plasma levels status at one or two month(s) after HSCT is an independent indicator for inferior OS, DFS, or TRM. A low sPD-1 plasma levels status at month three post HSCT is predictive for the onset of moderate/severe cGvHD. Thus, our study pinpoints the soluble inhibitory co-receptor PD-1 as a promising candidate molecule for the prediction of clinical HSCT outcome.

Malignant neoplasms originating from the bones of the foot: Predilection of hematological malignancies and sex-related and ethnic disparities in amputation.

PURPOSE: Neoplasms originating from the "small bones of the lower limb and the overlapping joints" are rare but portend a serious prognosis. Current study utilizes a population-based registry in the United States to characterize the malignancies of the foot. METHODS: National Cancer Institute's Surveillance, Epidemiology and End Result database from 1975 to 2017 was queried to report incidence and survival data in 514 patients in the Uited States. Kaplan-Meier and Cox Regression were used to determine the prognostic factors affecting survival. Chi square test was used to assess the correlation. RESULTS: Hematological malignancies constituted 14.8% of the entire cohort. Incidence of the foot neoplasms was 0.024 per 100 000 persons in 2017 and has not significantly changed since 1975 (p > 0.05). Disease-specific-5-year survival for the entire cohort was 73%. On multivariate analysis younger age groups, "localized" stage and extent of surgical resection were predictors of improved outcomes. A significant correlation was found between amputation with male sex and Hispanic ethnicity. CONCLUSIONS: The current study analyzes data from population-based registry reporting incidence and survival data for patients with neoplasms of the foot. Independent prognostic factors include age, stage and extent of surgical resection. Amputation was found to be associated with male sex and Hispanic ethnicity.

Ethical and Analytic Challenges With Genomic Sequencing of Relapsed Hematologic Malignancies Following Allogeneic Hematopoietic Stem-Cell Transplantation.

The implementation of precision medicine and next-generation sequencing technologies in the field of oncology is a novel approach being more widely studied and used in cases of high-risk primary and recurrent malignancies. Leukemias are the second most common cause of cancer-related mortality in children and the sixth most in adults. Relapsed leukemia represents a major component of the population that may benefit from genomic sequencing. However, ethical and analytic challenges arise when considering sequencing of biologic samples obtained from patients with relapsed leukemia following allogeneic hematopoietic stem-cell transplantation. Blood from the recipient after transplantation would include donor-derived cells and thus, genomic sequencing of recipient blood will interrogate the donor germline in addition to the somatic genetic profile of the leukemia cells and the recipient germline. This is a situation for which the donor will not have typically provided consent and may be particularly problematic if actionable secondary or incidental findings related to the donor are uncovered. We present the challenges raised in this scenario and provide strategies to mitigate this risk.

Soluble Interleukin-2 Receptor Index Predicts Outcomes After Cord Blood Transplantation.

BACKGROUND: Our previous study demonstrated that the soluble interleukin-2 receptor (sIL-2R) index, defined as the ratio of serum sIL-2R levels at neutrophil engraftment to that before conditioning, is a biomarker that can predict acute graft-vs-host disease (GVHD) after unrelated bone marrow transplantation. In the present study, we evaluated the significance of the sIL-2R index among patients who underwent cord blood transplantation (CBT). METHODS: We retrospectively analyzed 31 patients who underwent single-unit CBT as their first transplantation for hematologic malignancies. RESULTS: The median sIL-2R index was 4.2. The cumulative incidence of grade II to IV acute GVHD was not associated with the sIL-2R index. However, the cumulative incidence of relapse at 3 years after transplantation was significantly lower, with an sIL-2R index ≥ 3.7 than with an index < 3.7 (12.8% vs 50.0%; P = .04). As a result, the probability of overall survival at 3 years after transplantation was significantly higher in the former group than in the latter (79.8% vs 20.0%; P < .01). Only the dose of corticosteroid administered in the pre-engraftment period influenced the sIL-2 index. CONCLUSION: The sIL-2R index can predict the incidence of relapse and probability of survival after CBT, possibly reflecting a graft-vs-leukemia effect.

Mortality After General Surgery Among Hospitalized Patients With Hematologic Malignancy.

BACKGROUND: Hospitalized patients with hematologic malignancies (HMs) may require abdominal operations for complications of malignancy, treatment sequelae, or unrelated abdominal pathology. We determined predictors of mortality after emergency general surgery for patients with HM using national-level data. MATERIALS AND METHODS: We analyzed the 2010-2014 National Inpatient Sample for International Classification of Disease, Ninth Revision, Clinical Modification codes for HM and abdominal operations, comparing adult patient encounters with abdominal operations with HM to those without HM. Multivariate logistic regression was performed to identify predictors of mortality. RESULTS: Of the 7.9 million adult inpatient encounters where abdominal surgery was performed, 82,187 (1%) had concomitant diagnoses of HM. Mortality among patient encounters with HM was significantly higher than without HM (9.0% versus 2.0%; P < 0.0001). Patient encounters with HM and surgery and a diagnosis of acute abdominal pain had mortality rates as high as 41%. The median standardized risk ratio for death after the top 25 general surgery procedures was 2.9 (interquartile range: 2.2-3.8) among patients with HM. In adjusted analyses, odds of mortality among patients with HM undergoing surgery were increased by concomitant acute abdominal pain diagnosis (odds ratio [OR] = 2.6; P < 0.0001), coagulopathy (OR = 2.0; P < 0.0001), aplastic anemia (OR = 1.7; P < 0.0001), peripheral vascular disease (OR = 1.4; P = 0.001), and weight loss (OR = 1.3; P < 0.0001). CONCLUSIONS: Although uncommon, surgery on patients with HM is associated with mortality rates nearly five times higher than the general surgical population. Patients with HM requiring surgical intervention may be at particularly high odds of death and postoperative complications.

A prospective study on the long-term outcome of prepubertal and pubertal boys undergoing testicular biopsy for fertility preservation prior to hematologic stem cell transplantation.

BACKGROUND: Few studies have reported the long-term outcomes of prepubertal and pubertal boys undergoing testicular biopsy for fertility preservation (FP). PROCEDURE: This prospective longitudinal study examined 21 boys (aged 1.5-14.5 years) who underwent testicular biopsy for FP prior to allogeneic (n = 20) or autologous (n = 1) hematological stem cell transplantation (HSCT) between 2003 and 2010. During counseling, pubertal boys were encouraged to produce a sperm sample by masturbation , while prepubertal boys were presented with surgical testicular tissue retrieval as an option for experimental FP. Clinical outcomes included postoperative complications, pubertal development, and sex-hormone levels. Survivors approaching adulthood were encouraged to provide semen samples. RESULTS: Twenty boys, including 14 in prepuberty and six in early puberty (Tanner stage 2-3), underwent open testicular biopsies. Two pubertal biopsies contained mature sperms, which were cryopreserved. Testicular tissue was vitrified in the remaining 18 cases. One pubertal boy (Tanner stage 4) underwent percutaneous testicular sperm aspiration and sperms obtained were cryopreserved. Postoperative complications (hematoma or infection) were rare. Overall, 14 boys survived >5 years (mean follow-up after HSCT, 7.2 years) and 11 showed advanced puberty. Semen samples were provided by five boys and obtained sperm were cryopreserved from two. Individuals at adulthood had normal testosterone levels but subnormal testicular size, high follicle stimulating hormone, and low inhibin B and anti-Müllerian hormone levels. CONCLUSION: No long-term risks were detected during continuous clinical follow-up. Experimental testicular biopsies for FP were well accepted by the patients and families, despite the absence of methods to use prepubertal tissue for fertility treatment.

Hyperferritinemia and acute kidney injury in pediatric patients receiving allogeneic hematopoietic cell transplantation.

BACKGROUND: Acute kidney injury (AKI) often occurs in pediatric patients who received allogeneic hematopoietic cell transplantation (HCT). We evaluated the risk and effect of HCT-related AKI in pediatric patients. METHODS: We retrospectively studied the survival and renal outcome of 69 children 100 days and 1-year posttransplant in our institution in 2004-2016. Stage-3 AKI developed in 34 patients (49%) until 100 days posttransplant. RESULTS: The 100-day overall survival (OS) rates of patients with stage-3 AKI were lower than those without it (76.5% vs. 94.3%, P = 0.035). The 1-year OS rates did not differ markedly between 21 post-100-day survivors with stage-3 AKI and 29 without it (80.8% vs. 87.9%, P = 0.444). The causes of 19 deaths included the relapse of underlying disease or graft failure (n = 11), treatment-related events (4), and second HCT-related events (4). Underlying disease of malignancy (crude hazard ratio (HR) 5.7; 95% confidence interval (CI), 2.20 to 14.96), > 1000 ng/mL ferritinemia (crude HR 4.29; 95% CI, 2.11 to 8.71), stem cell source of peripheral (crude HR 2.96; 95% CI, 1.22 to 7.20) or cord blood (crude HR 2.29; 95% CI, 1.03 to 5.06), and myeloablative regimen (crude HR 2.56; 95% CI, 1.24 to 5.26), were identified as risk factors for stage-3 AKI until 100 days posttransplant. Hyperferritinemia alone was significant (adjusted HR 5.52; 95% CI, 2.21 to 13.76) on multivariable analyses. CONCLUSIONS: Hyperferritinemia was associated with stage-3 AKI and early mortality posttransplant. Pretransplant iron control may protect the kidney of pediatric HCT survivors.

Spinal Cord Compression Caused by Fibroblastic Reticular Cell Tumor (FRCT) Originating from Thoracic Spine.

BACKGROUND: The authors present the first reported case of a fibroblastic reticular cell tumor (FRCT) presenting with spinal cord compression. FRCTs are the rarest subset of dendritic cell tumors, a specific group of hematologic malignancies. FRCTs reportedly behave similar to low-grade sarcomas as opposed to malignant tumors. CASE DESCRIPTION: A 45-year-old female patient presented with a 2-and-a-half week history of a flu-like illness and 1 week history of lower limb imbalance. Magnetic resonance imaging revealed an extradural lesion at T3/4 compressing the spinal cord. Initially, the patient was presumed to have metastatic spinal cord compression, and she underwent a decompressive thoracic laminectomy with debulking of the lesion with follow-up adjuvant radiotherapy. However, histology identified a unique primary FRCT originating from spine, not secondary metastatic spinal cord compression. There were no histologically aggressive features likely contributing to the favorable outcome following surgery and adjuvant radiotherapy. Her postoperative recovery was unremarkable, and she recovered fully. CONCLUSIONS: Although rare, we report the first case of FRCT originating in the spine causing spinal cord compression. The clinical presentation of the case, histologic features of FRCT, and the treatment options are reviewed.

The long-term outcomes of modified Harrington procedure using antegrade pins for periacetabular metastasis and haematological diseases.

AIMS: The aim of this study was to present the long-term surgical outcomes, complications, implant survival, and causes of implant failure in patients treated with the modified Harrington procedure using antegrade large diameter pins. PATIENTS AND METHODS: A cohort of 50 consecutive patients who underwent the modified Harrington procedure for periacetabular metastasis or haematological malignancy between January 1996 and April 2018 were studied. The median follow-up time for all survivors was 3.2 years (interquartile range 0.9 to 7.6 years). RESULTS: The five-year overall survival rate was 33% for all the patients. However, implant survival rates were 100% and 46% at five and ten years, respectively. Eight patients survived beyond five years. There was no immediate perioperative mortality or complications. A total of 15 late complications occurred in 11 patients (22%). Five patients (10%) required further surgery to treat complications. The most frequent complication was pin breakage without evidence of acetabular loosening (6%). Two patients (4%) underwent revision for aseptic loosening at 6.5 and 8.9 years after surgery. Ambulatory status and pain level were improved in 83% and 89%, respectively. CONCLUSION: The modified Harrington procedure for acetabular destruction has low complication rates, good functional outcome, and improved pain relief in selected patients Cite this article: Bone Joint J 2019;101-B:1557-1562.

Molecular and cytogenetic characteristics of myeloid malignancies following luminal gastrointestinal cancer.

PURPOSE: Luminal gastrointestinal tract cancers (LGC) are common malignancies, and many patients can achieve long-term responses with surgery, cytotoxic and/or targeted therapies, and radiation. The long-term follow-up for patients with durable disease control has not been fully characterized, including subsequent malignancies. Such cases have not been comprehensively described. PATIENTS AND METHODS: We identified patients evaluated for myeloid malignancies (MyM) who had a prior LGC at our institution over a 35-year period. Patient, disease, and treatment information was collected for analysis. Cytogenetic risk profiles were designated according to the Revised International Prognostic Scoring System for MDS and the European LeukemiaNet Guidelines for AML. RESULTS: 66 patients were included in our cohort with 71 prior LGC diagnoses, including three patients with multiple LGCs. 31 cases were treated with surgery alone, and 37 patients received chemotherapy. The median age at diagnosis of MyM was 71.8 years (range, 36.2-90.5), with median duration between initiation of treatment of LGC and diagnosis MyM of 7.9 years (range 0.005-38.8). Intermediate or adverse (AML)/poor-very poor (MDS) cytogenetic risk was common, occurring in 43% of MDS patients and 100% of AML patients; deletion 5q was the most common cytogenetic abnormality overall. DNMT3A mutations were the most common molecular alteration (6 patients with 7 mutations). CONCLUSIONS: Among patients with MyM following LGC, a high proportion harbored cytogenetic changes, many of which were adverse or poor-risk. Deletion 5q and mutated DNMT3A were the most common abnormalities identified.

Haploidentical hematopoietic cell and kidney transplantation for hematological malignancies and end-stage renal failure.

At Massachusetts General Hospital, we pioneered simultaneous hematopoietic cell (HCT)/kidney transplantation from HLA-identical related donors for the treatment of hematological malignancies with end-stage renal failure. We have now extended this to HLA-haploidentical donors in a pilot trial. Six recipients, 5 of whom were conditioned with fludarabine, cyclophosphamide, and total-body irradiation, underwent combined HCT/kidney transplantation from haploidentical donors; graft-versus-host disease (GVHD) prophylaxis included post-HCT cyclophosphamide, tacrolimus, and mycophenolate mofetil. One patient died as a result of complications of fludarabine neurological toxicity. No neurological toxicity was observed in subsequent patients who received lower fludarabine doses and more intense postfludarabine dialysis. There were no cases of grade 2 to 4 acute GVHD and 1 case of moderate chronic GVHD by 12 months. One patient experienced relapse of multiple myeloma at 30 months after HCT and died 4 years posttransplantation. Overall, 4 of 6 patients remain alive, without disease relapse and with long-term renal rejection-free survival. This trial was registered at www.clinicaltrials.gov as #NCT01758042.

Laparoscopic splenectomy in malignancies: is safe and feasible?

BACKGROUND: Laparoscopic splenectomy (LS) is considered the treatment of choice for benign hematologic diseases of the spleen. However, the role of LS in malignancies is still controversial. Technical difficulties, hemorrhagic risk, the need of pathological characterization of malignant disease, may be considered contraindications to LS in malignancies. This study aims to verify the efficacy and feasibility of LS for hematologic malignancies. METHODS: One hundred and forty-five patients underwent LS for hematologic disease and were retrospectively shared in two groups: Group A (N.=83) patients with preoperative diagnosis of benign hematologic disease and Group B (N.=62) with malignancies. Bipolar spleen diameter, mean operative time, conversion rate and causes, complications and need of transfusion were evaluated. RESULTS: Median splenic diameter was greater in Group B than in Group A with a statistically significant difference (P<0.005), and the number of accessory mini-laparotomies (P<0.005) and the conversion rate (P=0.024) in the group of patients with a diagnosis of malignancy were also higher. The mean operative time was 117.6 minutes in group A and 148.1 minutes in Group B (P<0.005). Besides, there were no significant differences relative to intraoperative and postoperative transfusions and the incidence of postoperative complications. No perioperative mortality occurred. CONCLUSIONS: The analysis of our data highlights that LS for hematologic malignancies is effective and feasible even if it associated with higher conversion rate due to splenomegaly and difficult hilum dissection. Besides, no differences in the patient outcome were highlighted. LS may be considered a safe procedure in the treatment of haematological malignancies of the spleen.

An unusual complication of sacral nerve root injury following bone marrow harvesting: a case report.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) remains an important therapeutic option for many hematologic malignancies. Bone marrow harvesting from an appropriate donor must be conducted for hematopoietic stem cell transplantation (HSCT). Many previous studies show complications of the recipient after hematopoietic stem cell transplantation (HSCT). However, complications of the donor after bone marrow harvesting are rare. We here report a unique case of a patient who developed sacral nerve root injury after bone marrow harvesting. CASE PRESENTATION: A 26-year-old man was admitted to our medical center complaining of acute onset painful burning and tingling sensation at the left posterior thigh and calf. He was a bone marrow donor for his brother's bone marrow transplantation. He had underwent a bone marrow harvesting procedure two days before admission as a bone marrow donor, using both posterior superior iliac spine (PSIS) as the puncture site. Pelvic magnetic resonance image (MRI) showed enhancement around the left S2 nerve root in T1 and T2-weighted images. Nerve conduction studies (NCS) revealed normal conduction velocity and amplitude on both lower extremities. Electromyography (EMG) presented abnormal spontaneous activity and neurogenic motor unit potentials on the S2-innervated intrinsic foot muscle and gastrocnemius, soleus muscle on the left. The patient was treated with pregabalin for pain control. The patient was followed up after 3, 6, and 12 months. Neuropathic pain improved to Visual Analogue Scale (VAS) 1, and recovery state was confirmed by re-innervation patterns of motor unit potentials in electromyography. CONCLUSION: Bone marrow harvesting is a relatively safe procedure. However, variable complications may occur. Accurate anatomical knowledge and carefulness are required to avoid sacral nerve root injury when performing the bone marrow harvesting procedure.