Norman Maldonado

Myeloproliferative Neoplasm (MPN) Symptom Assessment Form Total Symptom Score: Prospective International Assessment of an Abbreviated Symptom Burden Scoring System Among Patients With MPNs

PURPOSE Myeloproliferative neoplasm (MPN) symptoms are troublesome to patients, and alleviation of this burden represents a paramount treatment objective in the development of MPN-directed therapies. We aimed to assess the utility of an abbreviated symptom score for the most pertinent and representative MPN symptoms for subsequent serial use in assessing response to therapy. PATIENTS AND METHODS The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) was calculated as the mean score for 10 items from two previously validated scoring systems. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. RESULTS MPN-SAF TSS was calculable for 1,408 of 1,433 patients with MPNs who had a mean score of 21.2 (standard deviation [SD], 16.3). MPN-SAF TSS results significantly differed among MPN disease subtypes (P<.001), with a mean of 18.7 (SD, 15.3), 21.8 (SD, 16.3), and 25.3 (SD, 17.2) for patients with essential thrombocythemia, polycythemia vera, and myelofibrosis, respectively. The MPN-SAF TSS strongly correlated with overall quality of life (QOL; r=0.59; P<.001) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) functional scales (all P<.001 and absolute r≥0.50 except social functioning r=0.48). No significant trends were present when comparing therapy subgroups. The MPN-SAF TSS had excellent internal consistency (Cronbachs α=.83). Factor analysis identified a single underlying construct, indicating that the MPN-SAF TSS is an appropriate, unified scoring method. CONCLUSION The MPN-SAF TSS is a concise, valid, and accurate assessment of MPN symptom burden with demonstrated clinical utility in the largest prospective MPN symptom study to date. This new prospective scoring method may be used to assess MPN symptom burden in both clinical practice and trial settings.

Hyperinfection syndrome with Strongyloides stercoralis.

Abstract Infection with the parasitic nematode,Strongyloides stercoralis, can lead to death in patients with various clinical disorders. Alteration of the parasite—host relationship may lead to hyp...

Pyoderma gangrenosum treated with6-mercaptopurine and followed by acute leukemia†

A 7-year-old boy presented with pyoderma gangrenosum. Extensive studies failed to show an etiological agent. Therapy with antibiotics, antifungal agents, topical medications, and corticosteroids did not result in healing of his skin lesions. He had hypergammaglobulinemia with increase in all of the three main immunoglobulins, and plasmacytosis of the bone marrow. Treatment with 6-mercaptopurine resulted in complete healing of the skin lesions. One year after cessation of therapy he developed acute leukemia. The association of immunoglobulin disorders with pyoderma gangrenosum and the relationship between autoimmune diseases, immunosuppressive therapy, and the development of leukemias and lymphomas are discussed.

Congenital isolated defect of folic acid absorption

A Caucasian girl with persistent diarrhea and severe megaloblastc anemia diagnosed at age three months failed to respond to oral treatment with folic acid, but there was prompt hematologic and gastrointestinal response following intramuscular administration of folic acid. Evaluation at age 11 years revealed signs of folate deficiency and low serum and whole blood folate avalues. Serum folic acid values were not increased during folic acid and citrovorum factor absorption tests or following administration of 40 or 100 mg. of folic acid orally on separate occasions. Intestinal absorption test results and the jejunal and gastric mucosa were normal. These studies demonstrate an alteration in the normal mechanism of absorption of both physiologic and pharmacologic doses of pteroylglytamic acid.

Normal pregnancy in multiple myeloma treated with cyclophosphamide

We have studied a young woman with multiple myeloma who became pregnant while on oral cyclophosphamide. She had a normal pregnancy and was delivered by cesarean section because of fetal distress. The infant was healthy at birth and had an “M” component in serum of cord blood similar to his mothers. This abnormal protein disappeared when the infant was evaluated at 2 years of age. We conclude that the abnormal IgG in multiple myeloma can cross the placental barrier, but the newborn did not have any detectable disease. Chromosomal studies on the newborn were normal. Cyclophosphamide therapy produced no evident congenital abnormalities. A review of three additional instances of pregnancy and multiple myeloma is made, with a reveiw of the pertinent literature concerning pregnancy and cyclophosphamide therapy.

Long-Term Follow-Up of Antibiotic-Treated Tropical Sprue

Abstract Clinical status and intestinal structure and function were evaluated in 17 patients with tropical sprue who, 5 years or more in the past, had been treated with antibiotic agents for at lea...

Symptomatic Profiles of Patients With Polycythemia Vera: Implications of Inadequately Controlled Disease

PURPOSE Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) associated with disabling symptoms and a heightened risk of life-threatening complications. Recent studies have demonstrated the effectiveness of JAK inhibitor therapy in patients with PV patients who have a history of prior hydroxyurea (HU) use (including resistance or intolerance), phlebotomy requirements, and palpable splenomegaly. We aimed to determine how these features contribute alone and in aggregate to the PV symptom burden. PATIENTS AND METHODS Through prospective evaluation of 1,334 patients with PV who had characterized symptom burden, we assessed patient demographics, laboratory data, and the presence of splenomegaly by disease feature (ie, known HU use, known phlebotomy requirements, splenomegaly). RESULTS The presence of each feature in itself is associated with a moderately high symptom burden (MPN symptom assessment form [SAF] total symptom score [TSS] range, 27.7 to 29.2) that persists independent of PV risk category. In addition, symptoms incrementally increase in severity with the addition of other features. Patients with PV who had all three features (PV-HUPS) faced the highest total score (MPN-SAF TSS, 32.5) but had similar individual symptom scores to patients with known HU use (PV-HU), known phlebotomy (PV-P), and splenomegaly (PV-S). CONCLUSION The results of this study suggest that patients with PV who have any one of the features in question (known HU use, known phlebotomy, or splenomegaly) have significant PV-associated symptoms. Furthermore, it demonstrates that many PV symptoms remain severe independent of the number of features present.

Hemostatic Abnormalities Associated With Monoclonal Gammopathies

To confirm and expand previous observations about the association of monoclonal gammopathies with hemostatic defects, a prospective evaluation was made in 42 patients with lymphoplasmacytic disorders. The incidence of bleeding complications was low, despite the diversity of abnormal hemostatic tests observed in these patients. Patients with myeloma frequently had abnormal coagulation tests, including thrombin time (64%), fibrin degradation products (32%), platelet aggregation tests with different agonist (30% to 55%), and bleeding time (22%). The lack of platelet response to ristocetin and normal ristocetin cofactor activity in four patients with myeloma may suggest a Bernard-Soulier-type defect. Serum viscosity was negatively correlated with platelet aggregation with collagen, ristocetin, and adenosine diphosphate. In patients with immunoglobulin myeloma, there was a positive correlation between an increased viscosity and a prolonged thrombin time. This study demonstrates the wide variety of coagulation abnormalities in lymphoplasmacytic disorders, usually without significant clinical implications.

Tropical sprue in children

Eleven Puerto Rican children with chronic diarrhea, intestinal malabsorption, abnormal jejunal mucosa, megaloblastic bone marrow, and malnutrition have been studied. The patients were treated with folic acid alone or folic acid and vitamin B 12 ; one patient received oxytetracycline. The results were good to excellent in all but one of the children. This symptomatic, hematologic, and gastrointestinal responses were similar to those reported in adult patients with tropical sprue. The evidence presented here suggests that this syndrome in children is the same disease as tropical sprue in adults manifested at an early age, sometimes as early as the first year of life. The etiology of this disease in children, as well as in adults, remains unknown.

Associations between gender, disease features and symptom burden in patients with myeloproliferative neoplasms: an analysis by the MPN QOL International Working Group.

The myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and myelofibrosis, are distinguished by their debilitating symptom profiles, life-threatening complications and profound impact on quality of life. The role gender plays in the symptomatology of myeloproliferative neoplasms remains under-investigated. In this study we evaluated how gender relates to patients’ characteristics, disease complications and overall symptom expression. A total of 2,006 patients (polycythemia vera=711, essential thrombocythemia=830, myelofibrosis=460, unknown=5) were prospectively evaluated, with patients completing the Myeloproliferative Neoplasm-Symptom Assessment Form and Brief Fatigue Inventory Patient Reported Outcome tools. Information on the individual patients’ characteristics, disease complications and laboratory data was collected. Consistent with known literature, most female patients were more likely to have essential thrombocythemia (48.6% versus 33.0%; P<0.001) and most male patients were more likely to have polycythemia vera (41.8% versus 30.3%; P<0.001). The rate of thrombocytopenia was higher among males than females (13.9% versus 8.2%; P<0.001) and males also had greater red-blood cell transfusion requirements (7.3% versus 4.9%; P=0.02) with shorter mean disease duration (6.4 versus 7.2 years, P=0.03). Despite there being no statistical differences in risk scores, receipt of most therapies or prior complications (hemorrhage, thrombosis), females had more severe and more frequent symptoms for most individual symptoms, along with overall total symptom score (22.8 versus 20.3; P<0.001). Females had particularly high scores for abdominal-related symptoms (abdominal pain/discomfort) and microvascular symptoms (headache, fatigue, insomnia, concentration difficulties, dizziness; all P<0.01). Despite complaining of more severe symptom burden, females had similar quality of life scores to those of males. The results of this study suggest that gender contributes to the heterogeneity of myeloproliferative neoplasms by influencing phenotypic profiles and symptom expression.