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Biomedical subjects

M A Gertz

Publications and source records attributed to M A Gertz.

At least 19 recordsLinked to original sources
PubMed2002

Splenectomy for immune thrombocytopenic purpura: long-term results and treatment of postsplenectomy relapses.

Information regarding prognostic determinants of outcome after splenectomy for adult immune thrombocytopenic purpura (ITP) and the management of postsplenectomy relapse is limited. Among 140 adult patients with ITP who had therapeutic splenectomy at our institution, 88% achieved either a complete (platelets > 150 x 10(9)/l) or a partial (platelets > or = 50 x 10(9)/l) response that was sustained for at least 1 month. At 3, 6, and 12 months after splenectomy, time-adjusted complete response rates were 77%, 71%, and 74%, respectively. The 5-year relapse-free survival was 75%; all but three relapses occurred within 2 years of splenectomy. In multivariate analysis, younger age and higher peak postsplenectomy platelet counts were significantly associated with a favorable response to splenectomy. None of several preoperative or perioperative variables was predictive of a relapse after an initial response to splenectomy. Corticosteroids, danazol, vincristine, and cyclophosphamide were often effective in the treatment of patients who were either refractory to or had a relapse after splenectomy. One patient responded to rituximab after not responding to corticosteroids, azathioprine, and vincristine. After a median follow-up of 37.5 months (range: 0-183) from splenectomy, there were 25 deaths, including 2 from postoperative complications, 1 from gastrointestinal bleeding related to thrombocytopenia, and 1 from overwhelming sepsis related to the splenectomized state. The current study provides additional data on both the long-term outcome of splenectomy in adults with ITP and the management of postsplenectomy relapse.

Adolescent↗
PubMed2002

IL-1beta expression in IgM monoclonal gammopathy and its relationship to multiple myeloma.

We have shown that IL-1beta is not detectable in normal plasma cells but is produced by plasma cells from virtually all patients with multiple myeloma (MM). To extend our earlier work, IL-1beta expression was determined in 13 newly diagnosed patients with IgM monoclonal gammopathy. Eleven patients with Waldenstrom's macroglobulinemia (WM) and two patients with IgM MM were investigated for IL-1beta expression by in situ hybridization (ISH). All patients with WM had bone marrow biopsies consistent with the diagnosis, an IgM M-protein in the serum, and subsequently required chemotherapy. Seven of 11 patients with WM had an M-protein >3 g/dl and five patients had bone surveys performed that were negative for osteolytic disease. Two patients were diagnosed with IgM MM because of the presence of significant osteolytic disease on a metastatic bone survey. ISH for kappa, lambda, and IL-1beta expression was performed on bone marrow aspirates from each of the 13 patients. None of the neoplastic cells from the 11 patients with WM showed detectable IL-1beta expression by ISH. However, the neoplastic cells from both patients with IgM MM expressed IL-1beta mRNA at high levels. This aberrant IL-1beta production may explain the presence of bone lesions in the patients with IgM MM.

Biopsy, Needle↗
PubMed2001

Translocations involving the immunoglobulin heavy-chain locus are possible early genetic events in patients with primary systemic amyloidosis.

Primary systemic amyloidosis (AL) is a plasma cell (PC) dyscrasia with clinical similarities to multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), but its molecular basis is poorly understood. Translocations at the immunoglobulin heavy-chain (IgH) locus, 14q32, are likely early genetic events in both MM and MGUS and involve several nonrandom, recurrent, partner chromosomes such as 11q13, 16q23, and 4p16.3. Given the similarities between MM, MGUS, and AL, bone marrow clonal PCs were evaluated in 29 patients with AL using interphase fluorescence in situ hybridization (FISH) combined with immunofluorescence detection of the cytoplasmic light-chain (cIg-FISH) for the presence of 14q32 translocations and the t(11;14)(q13;q32). Of 29 patients studied, 21 (72.4%) showed results compatible with the presence of a 14q32 translocation, and 16 (76.2%) of those had translocation (11;14)(q13;q32) for an overall prevalence of the abnormality of 55%. IgH translocations are common in AL, especially the t(11;14)(q13;q32).

Adult↗
PubMed2001

Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma.

Autologous stem cell transplantation (ASCT) improves survival in patients with previously untreated multiple myeloma (MM) and relapsed, chemotherapy-sensitive, aggressive non-Hodgkin lymphoma (NHL). Lower relapse rates seen in allogeneic stem cell transplantation have been related to early absolute lymphocyte count (ALC) recovery as a manifestation of early graft-verus-tumor effect. In ASCT, the relation between ALC recovery and clinical outcomes in MM and NHL was not previously described. This is a retrospective study of patients with MM and NHL who underwent ASCT at the Mayo Clinic between 1987 and 1999. The ALC threshold was determined at 500 cells/microL on day 15 after ASCT. The study identified 126 patients with MM and 104 patients with NHL. The median overall survival (OS) and progression-free survival (PFS) times for patients with MM were significantly longer in patients with an ALC of 500 cells/microL or more than patients with an ALC of fewer than 500 cells/microL (33 vs 12 months, P <.0001; 16 vs 8 months, P <.0003, respectively). For patients with NHL, the median OS and PFS times were significantly longer in patients with an ALC of 500 cells/microL or more versus those with fewer than 500 cells/microL (not reached vs 6 months, P <.0001; not reached vs 4 months, P <.0001, respectively). Multivariate analysis demonstrated day 15 ALC to be an independent prognostic indicator for OS and PFS rates for both groups of patients. In conclusion, ALC is correlated with clinical outcome and requires further study. (Blood. 2001;98:579-585)

Actuarial Analysis↗
PubMed2001

Eligibility for hematopoietic stem-cell transplantation for primary systemic amyloidosis is a favorable prognostic factor for survival.

PURPOSE: Based on the success of hematopoietic stem-cell transplantation (HSCT) for multiple myeloma, HSCT is being used to treat patients with primary systemic amyloidosis (AL). This article addresses the extent to which eligibility to undergo HSCT is a favorable prognostic feature and explores prognostic factors within the subset of eligible patients. PATIENTS AND METHODS: The Mayo Clinic amyloid database was queried for all patients with AL seen at the Mayo Clinic from 1983 through 1997 who would have been eligible for peripheral-blood stem-cell transplantation. Inclusion criteria included biopsy-proven amyloid, symptomatic disease, absence of a clinical diagnosis of multiple myeloma, age < or = 70 years, cardiac interventricular septal thickness < or = 15 mm, cardiac ejection fraction more than 55%, serum creatinine < or = 2 mg/dL, and direct bilirubin < or = 2.0 mg/dL. RESULTS: Median age was 56 years (range, 25 to 70) with 79 (34%) older than 60 years. One hundred patients had early cardiac involvement; 41, hepatic involvement; 167, renal involvement; and 39, nerve involvement. The 229 patients have had a median follow-up of 52 months, and 151 have died. The median survival was 42 months with 5- and 10-year survival rates of 36% and 15%, respectively. Important predictors of survival were size of M-component in 24-hour urine, number of involved organs, alkaline phosphatase, performance score, and weight loss. CONCLUSION: The same patients who are eligible for HSCT are a good-risk population who do relatively well with chemotherapy (median survival, 42 months), substantially better than the expected median survival of 18 months for all patients with AL. A randomized trial is needed to assess the true effect of HSCT.

Adult↗
PubMed2001

Prognostic factors and response to fludarabine therapy in patients with Waldenström macroglobulinemia: results of United States intergroup trial (Southwest Oncology Group S9003).

Current information on Waldenström macroglobulinemia (WM) is based on retrospective or single-institution studies of patients requiring therapy. Between 1992 and 1998, 231 patients with WM were enrolled in a prospective observational multicenter clinical trial. Of these, 182 patients with symptomatic or progressive disease were treated with 4 to 8 cycles of therapy with a purine nucleoside analogue, fludarabine (FAMP; 30 mg/m(2) of body-surface area daily for 5 days every 28 days). A serum beta2-microglobulin (beta2M) level below 3 mg/L and a hemoglobin level of at least 120 g/L (12 g/dL) at presentation predicted a lower likelihood of requiring therapy. The overall rate of response to FAMP therapy was 36% (95% confidence interval, 29%-44%), with 2% complete remissions. Patients who were 70 years old or older had a substantially lower likelihood of response (odds ratio, 0.34; P =.004) than younger patients. On multivariate analysis, a serum beta2M level of 3 mg/L or higher, hemoglobin level below 120 g/L, and serum IgM level below 40 g/L [4 g/dL] were significant adverse prognostic factors for survival. We developed a simple staging system for WM by using these variables and identified 4 distinct subsets of patients with estimated 5-year overall survival rates of 87%, 64%, 53%, and 22%, and 5-year progression-free survival rates of 83%, 55%, 33%, and 12%. Prognosis in WM is highly variable and serum beta2M was the dominant predictor of a need for therapy and of survival. FAMP has activity against WM. Our staging system may provide guidance for a risk-based approach to the treatment of WM.

Age Factors↗
PubMed2001

A high bone marrow plasma cell labeling index in stable plateau-phase multiple myeloma is a marker for early disease progression and death.

The plasma cell labeling index (PCLI) is a measure of plasma cell proliferative activity and is an important prognostic factor in newly diagnosed multiple myeloma (MM). Occasionally patients have been observed with stable, plateau phase MM with minimal numbers of residual light-chain-restricted monoclonal plasma cells, but a high PCLI. No data are available on the outcomes for such patients. Data from 57 patients with plateau phase MM and a marrow PCLI of more than 1.0% were compared with 105 matched control patients with MM with a marrow PCLI of less than 1.0%. All patients had less than 10% total plasma cells on marrow aspirate and biopsy. The median time to progression and overall survival were 8 months and 20 months, respectively, in the high PCLI group versus 39 months and 56 months, respectively, in the low PCLI group (P < .0001). These findings suggest that a high PCLI in patients with apparently stable, plateau phase MM is an adverse parameter that may predict a short time to disease progression and death.

Bone Marrow↗
PubMed2001

Clonal evolution in Waldenstrom macroglobulinemia highlights functional role of B-cell receptor.

The course of clonal evolution of 2 related clones in the blood of a patient with Waldenstrom macroglobulinemia (WM) indicates the functional importance for the expression of the B-cell receptor for the survival of these malignant cells. Protein and nucleotide sequencing of the paraproteins' variable regions revealed 2 predominant Vlambda and 2 VH sequences, each set comprised in the ratio 1:1.5. The 2 VH sequences and 2 Vlambda sequences shared the same VDJ and VJ junctional sequences, respectively, indicating that 2 malignant clones had evolved from a common ancestor. This is the first report on intraclonal heterogeneity in WM. Comparison of the Vlambda and VH sequences with the closest matching known germline genes showed that they contained approximately 10 somatic mutations each. The distribution and type of mutations demonstrate that mutations have continued to accumulate in the malignant clones and that selection has been operating to preserve immunoglobulin structure.

Base Sequence↗
PubMed2001

Methods for estimation of bone marrow plasma cell involvement in myeloma: predictive value for response and survival in patients undergoing autologous stem cell transplantation.

In myeloma, the bone marrow plasma cell percentage (BMPC%) is usually estimated independently on the aspirate, core biopsy, and plasma cell labeling index (PCLI) samples. This study was done to determine which of the 3 individual estimates correlates best with complete response (CR) and survival. Seventy-five consecutive patients who underwent SCT for relapsed myeloma were studied. The median BMPC% on the marrow aspirate, core biopsy, and PCLI studies were 20, 25, and 20, respectively. There was a significant correlation between the three methods, rho > 0.65, P < 0.001. However, in 8% of patients the BMPC% was different by an absolute value of 50% between methods. No individual method was predictive for CR. However, the highest estimate of the BMPC% among the three methods was a significant predictor of CR (P = 0.02). Survival following SCT was longer among patients with a low BMPC% (< or =60) by the PCLI method compared to those with higher values, median survival 23 versus 7 months, respectively, P = 0.02. PFS was also different, with survival times of 11 and 5 months, respectively, P = 0.003. Similar results were obtained when the highest estimate of the BMPC% was used in survival analysis (P = 0.02 and 0.004, respectively). Statistical significance was lower when the BMPC% on the aspirate or biopsy used in survival analysis. Compared to any individual method of estimating BMPC%, the highest estimate of the BMPC% is the best predictor of CR in myeloma. It is also prognostic for poor survival and PFS following SCT for myeloma. We recommend that all three methods of estimating BMPC% be routinely performed and that the highest value be used for prognostic purposes.

Adult↗
PubMed2001

Primary systemic amyloidosis: a cause of malabsorption syndrome.

PURPOSE: Although malabsorption syndrome is encountered frequently by general internists and gastroenterologists and is common to various underlying disease processes, primary amyloidosis is often overlooked during medical evaluation. We describe the diagnosis, natural history, and laboratory features of a subgroup of patients with primary amyloidosis who presented predominantly with gastrointestinal symptoms and with evidence of a malabsorption syndrome. SUBJECTS AND METHODS: We reviewed all patients diagnosed with amyloidosis and malabsorption syndrome who had been seen at the Mayo Clinic from 1960 through 1998. Nineteen patients with small bowel biopsy results showing primary amyloid and with laboratory evidence of a malabsorption syndrome were studied. RESULTS: The most common symptoms were diarrhea or steatorrhea in 95% of patients (n = 18), anorexia in 42% (n = 8), and dizziness in 32% (n = 6). The most common signs included weight loss in all 19 patients, with a median weight loss of 30 pounds (range, 2 to 134 pounds) and hypotension or orthostatic changes in 10 patients (53%). The median time from symptom onset to diagnosis was 7 months. Most patients had evidence of amyloid involvement of other organs. Only 3 patients (16%) were diagnosed correctly upon initial presentation. Serum or urine protein electrophoresis results were positive in 95% of patients (n = 18). Median survival was 11 months from histologic diagnosis. CONCLUSIONS: Primary systemic amyloidosis should be considered in the differential diagnosis of malabsorption syndrome. All patients over 30 years of age with a malabsorption syndrome should have screening serum and urine immunofixation before undergoing a small bowel biopsy.

Adult↗
PubMed2001

Fatal disseminated aspergillosis following sequential heart and stem cell transplantation for systemic amyloidosis.

Infectious complications are a major cause of morbidity and mortality in transplant recipients. We describe a case of fatal disseminated aspergillosis immediately following autologous peripheral stem cell reconstitution in a patient who had undergone orthotopic heart transplantation for systemic amyloidosis. The case described suggests that the infectious risks in patients undergoing these sequential procedures may be distinct from those occurring in patients undergoing either procedure independently. Potential prophylactic and therapeutic interventions are discussed. Since this experimental and evolving approach for the management of systemic amyloidosis is potentially applicable to a limited number of patients, multicenter collaboration may be needed to further define the infectious risks in this unique subset of transplant recipients.

Adult↗
PubMed2001

Prophylaxis of graft-versus-host disease with cyclosporine-prednisone is associated with increased risk of chronic graft-versus-host disease.

To determine the effect of two different graft-versus-host disease (GVHD) prophylactic regimens--cyclosporine with short course of methotrexate (CYA-MTX) and cyclosporine with prednisone (CYA-PRED)--on the incidence of chronic GVHD (cGVHD), we retrospectively reviewed the outcomes of 196 consecutive allogeneic related blood and marrow transplants performed at our institution utilizing one of these regimens. CYA-PRED was given to patients who were transplanted more recently because of concern about the increased risk of veno-occlusive disease of the liver, increased mucositis, and slower engraftment in patients receiving CYA-MTX. Prophylaxis with CYA-PRED was associated with a higher risk of development of cGVHD (risk ratio (RR) 3.5; 95% confidence intrerval (CI), 2.2-5.4). The proportion of patients with extensive disease among those developing cGVHD was higher in the CYA-PRED group (71%) than in the CYA-MTX group (57%), although this difference was not statistically significant. The cumulative probability of extensive cGVHD at 2 years was higher in the CYA-PRED group (RR 4.2, 95% CI, 2.4-7.4). Development of acute GVHD and cytomegalovirus mismatch were independent predictors of increased risk of cGVHD. We conclude that GVHD prophylaxis with CYA-PRED is associated with a higher overall rate of cGVHD compared to CYA-MTX. The type of GVHD prophylaxis should be considered when comparing the incidence of cGVHD reported in different studies.

Adolescent↗
PubMed2001

Peri-engraftment respiratory distress syndrome during autologous hematopoietic stem cell transplantation.

From 1987 to 1998, 19 of 416 patients (4.6%) who underwent autologous hematopoietic stem cell transplantation experienced peri-engraftment (within 5 days of neutrophil recovery) respiratory distress syndrome (PERDS) not attributable to infection, fluid overload, or cardiac dysfunction. The median time from stem cell infusion to onset of PERDS was 11 days (range 4-25). Risk of PERDS or its outcome was not predicted by any pre- or peri-transplant clinical or laboratory feature. The respective median white blood cell and platelet counts at first symptoms were 1.3 x 10(9)/l and 25 x 10(9)/l. No patients had an infectious etiology by bronchoalveolar lavage. Six of the 19 patients had alveolar hemorrhage, which was significantly correlated with high neutrophil count. PERDS was directly implicated in four deaths (21%). Eleven patients received high-dose corticosteroid therapy, including five of the six who required mechanical ventilation. Ten of these patients experienced clinical improvement, which occurred within 24 h in five. The rapid response to corticosteroid treatment and the fact that such therapy was delayed until after intubation in all the mechanically ventilated cases point to a therapeutic benefit.

Adolescent↗
PubMed2001

Successful treatment of POEMS syndrome with autologous hematopoietic progenitor cell transplantation.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a plasma cell dyscrasia that differs substantially from classic multiple myeloma. It is often associated with disabling polyneuropathy in younger patients. Current therapeutic approaches are frequently inadequate and leave many patients wheelchair-bound with significant deterioration in quality and length of life. We present the case of a young man with progressive disease despite conventional therapeutic approaches. We describe a novel approach to treatment with a bone-seeking radiopharmaceutical, samarium-153 ethylene diamine tetramethylene phosphonate ((153)Sm-EDTMP), followed by myeloablative chemotherapy with autologous hematopoietic progenitor cell reconstitution. This approach resulted in regression of the organomegaly and skin changes and in neurologic improvement both clinically and electrophysiologically. The patient progressed from being wheelchair-bound to independent ambulation. An aggressive approach should be considered in patients with POEMS syndrome in whom standard therapeutic measures fail.

Adult↗
PubMed2001

High incidence of gastrointestinal tract bleeding after autologous stem cell transplant for primary systemic amyloidosis.

Peripheral blood stem cell transplants have been associated with better response rates than conventional chemotherapy in patients with primary systemic amyloidosis. A higher incidence of gastrointestinal (GI) tract bleeding has been observed among amyloidosis patients undergoing peripheral stem cell transplantation. We retrospectively reviewed the medical records of such patients to identify those who had GI tract bleeding in the post-transplant period. Forty-five patients were studied. Nine patients had GI tract bleeding in the post-transplant period. The median post-transplant duration to onset of bleeding was 9.5 days (range 1 to 48 days). Three patients had lower GI tract bleeding, two had upper GI tract bleeding, and four had both. Diffuse esophagitis and gastritis were the most common findings on endoscopy. There were no correlations among the age, platelet nadir, or CD34 count of the graft and the risk of bleeding. Women were more likely to have GI tract bleeding (P = 0.015), as were patients with slow platelet engraftment (P = 0.02). Patients with multiorgan involvement and those on hemodialysis appeared to be at a higher risk of GI tract bleeding. The mean post-transplant hospital stay for those with GI tract bleeding was 37 days compared with 14.5 days for those who did not have GI tract bleeding (P = 0.0047).

Adult↗
PubMed2001

Effect of slow lymphocyte recovery and type of graft-versus-host disease prophylaxis on relapse after allogeneic bone marrow transplantation for acute myelogenous leukemia.

Allogeneic BMT is potentially curative for patients with acute myelogenous leukemia (AML) in first remission. However, many patients relapse after transplantation. Various immunotherapeutic options have been attempted with variable success in preventing relapse. Early identification of patients at high risk for relapse could allow prompt intervention. We examined the effect of slow lymphocyte recovery after sibling-matched allogeneic BMT on the risk of relapse in patients with AML. We also examined the effect of prednisone-containing GVHD prophylaxis on the rate of lymphocyte recovery. Patients with absolute lymphocyte count (ALC) <150 x 10(6)/l by day +30 had a 3.5-fold higher risk of relapse (P = 0.0088) and a lower overall survival (P = 0.0079) than patients with a higher ALC. We did not find correlation between lymphocyte count determined earlier in the post-transplantation course (day +21) and the risk of relapse. Patients receiving prednisone had a significantly lower ALC at day +30 than those who did not receive prednisone (289 vs 549 x 10(6)/l, P = 0.002). We conclude that a slow lymphocyte recovery after allogeneic BMT for AML is strongly predictive of subsequent relapse and that the type of GVHD prophylaxis should be considered when analyzing lymphocyte recovery.

Adolescent↗
PubMed2001

Thalidomide for previously untreated indolent or smoldering multiple myeloma.

We conducted a clinical trial of thalidomide as initial therapy for asymptomatic smoldering (SMM) or indolent multiple myeloma (IMM). Sixteen patients were studied. Thalidomide was given orally at a dose of 200 mg/day for 2 weeks, and then increased as tolerated by 200 mg/day every 2 weeks to a maximum dose of 800 mg/day. Bone marrow microvessel density (MVD) and angiogenesis grading were estimated using CD34 immunostaining. Six patients had a confirmed response to therapy with at least 50% or greater reduction in serum and urine monoclonal (M) protein. When minor responses (25-49%) decrease in M protein concentration) were included, 11 of 16 patients (69%) responded to therapy. Major grade 3-4 toxicities included two patients with somnolence, and one patient each with syncope and neutropenia. Pre-treatment MVD was not a significant predictor of response to therapy, median MVD 4 and 12 in responders and non-responders respectively, P = 0.09. We conclude that thalidomide has significant activity in the treatment of newly diagnosed SMM/IMM. However, we do not recommend treatment with thalidomide at this stage since some patients with SMM/IMM can be stable for several months or years without any therapy. Additional randomized trials are needed to determine if thalidomide will delay progression to active multiple myeloma.

Administration, Oral↗