Hematologic Manifestations of Nutritional Deficiencies: Early Recognition is Essential to Prevent Serious Complications.

Nutritional deficiencies, including deficiencies of vitamin B12, copper, and vitamin C, may result in cytopenias and hematologic symptoms. Early recognition of these deficiencies is imperative for prompt treatment and improvement in hematologic and other manifestations. We describe 5 cases which illustrate the hematologic manifestations of nutritional deficiencies and challenges to initial diagnosis and management. Supplementation of the deficient vitamin or micronutrient in all of these cases resulted in rapid resolution of cytopenias, hemorrhage, and other associated hematologic symptoms. We also review other nutritional deficiencies that manifest with hematologic symptoms and compile recommendations on treatment and expected time to response.

Herbal approach in the treatment of pancytopenia.

Pancytopenia is a health condition in which there is a reduction in the amount of leucocytes, erythrocytes and thrombocytes. If more than one of the blood cells is low then the condition is called as bicytopenia. The pancytopenic condition is observed in treatment of diseased conditions like thalassemia and hepatitis C. Iatrogenically pancytopenia is caused by some antibiotics and anti-HCV drugs. Medical conditions like aplastic anaemia, lymphoma, copper deficiency, and so forth can also cause pancytopenia. Pancytopenia can in turn decrease the immunity of the person and thereby can be fatal. Current therapies for pancytopenia include bone marrow stimulant drugs, blood transfusion and bone marrow transplant. The current therapies are very excruciating and have long-term side-effects. Therefore, treating these condition using herbal drugs is very important. Herbs like wheatgrass, papaya leaves and garlic are effective in treating single lineage cytopenias. The present review is focused on the potential effects of natural herbs for the treatment of pancytopenia.

[Severe Therapy-Related Pancytopenia Caused by UFT and LV in a Patient with Ascending Colon Cancer].

We report a case of a 79-year-old man who developed severe therapy-related pancytopenia from tegafur uracil(UFT)and Leucovorin(LV)as adjuvant chemotherapy for ascending colon cancer. Laparoscopic right hemicolectomy resection was performed for the ascending colon cancer. Pathohistological analysis revealed that the ascending colon tumor was moderately differentiated tubular adenocarcinoma(T3, N1, M0, and Stage III a). Postoperative adjuvant chemotherapy with UFT and LV was administered. After 2 courses of chemotherapies, severe thrombocytopenia(Grade 4)and neutropenia(Grade 4)were noted. Platelet and granulocyte-colony stimulating factor(G-CSF)were transfused. Furthermore, red blood cell transfusions were given for anemia(Grade 3). Dihydropyrimidine dehydrogenase(DPD)deficiency was suspected as the cause of the pancytopenia, and the ratio of dihydrouracil(DHU)and uracil(URA)was measured. However, the result was negative for DPD deficiency. Bone marrowaspiration revealed that therapy-related leukemia(TRL)and therapy-related myelodysplastic syndrome(T-MDS)were not the causes of the pancytopenia either. A total of 230 units of platelet transfusions and 20 units of red blood cell transfusions have been given for 32 weeks, and the patient currently requires routine blood transfusions. Fortunately, infection and bleeding never occurred. Subsequently, the patient should be monitored carefully.

Reversible pancytopenia following the consumption of decoction of Ganoderma neojaponicum Imazeki.

The Ganoderma species are mushrooms used for herbal medicinal purposes in northeast Asia. Two cases of simultaneous reversible pancytopenia following the consumption of decoction of Ganoderma neojaponicum Imazeki are presented. Other than decoction of G. neojaponicum Imazeki no cause of pancytopenia could be identified. The patients recovered fully after conservative treatment. People who consume herbal medicines are often not aware of their side effects. Patients should be knowledgeable regarding the possible side effects of Ganoderma prior to its consumption.

Early-onset pancytopenia and skin ulcer following low-dose methotrexate therapy.

Pancytopenia is a rare but serious adverse effect of low-dose methotrexate (MTX) sodium therapy, and this case report describes a very early-onset of pancytopenia and cutaneous lesions after three days of ingestion. A 64-year-old man was presented to Emergency Department with weakness, fever, poor appetite, nausea, and vomiting after he had had accidentally ingested MTX tablets (2.5 mg) twice a day for the last three days. On initial examination, several painful lesions in his oral mucosa and a cutaneous ulceration on his right foot were also observed. He had severe pancytopenia, poor kidney functions, and abnormal coagulation parameters. The blood level of MTX was found to be within therapeutic range. He was treated with leucovorine, intravenous antibiotics, and appropriate blood transfusions; he was discharged from hospital without any sequela. Pancytopenia associated with low-dose (cumulative dose of 15 mg in 3 days) MTX therapy had not been reported previously. The Naranjo probability scale showed pancytopenia and skin ulcer associated with low-dose MTX therapy as probable adverse reactions. Risk factors for pancytopenia such as renal insufficiency, hypoalbuminemia, low folate levels, concomitant infections, concomitant use of drugs, and folate supplementation were not identified in our patient. Although pancytopenia associated with low-dose MTX therapy is not expected as early as 3 days after initiation of the therapy, physicians should also be aware of this life threatening adverse effect during the very first days of MTX therapy for rheumatoid arthritis patients.

Cytokines in combination to treat radiation-induced myelosuppresssion: evaluation of SCF + glycosylated EPO + pegylated G-CSF as an emergency treatment in highly irradiated monkeys.

Multicytokine therapy may be useful to counteract radiation-induced myelosuppression. We assessed the stem cell factor + glycosylated erythropoietin + pegylated granulocyte colony-stimulating factor combination (SEG) as an emergency treatment. SEG in highly irradiated monkeys efficacy appeared to be restricted to granulopoiesis. Early administration of Erythropoietin did not prevent radiation-induced anemia.

[Successful off-pump coronary artery bypass for a patient with aplastic anemia].

We report a 61-year-old man with aplastic anemia who underwent successful off-pump coronary artery bypass (OPCAB) after being admitted for angina pectoris. Coronary angiography showed severe stenosis of the left main coronary artery. Preoperative WBC was 2,200/microl, neutrophil 704/microl, Hb 8.1g/dl, and PLT 16,000/microl. We conducted OPCAB on double vessels using left internal thoracic and radial artery grafts. Thirty units of platelets were transfused intraoperatively with little perioperaive hemorrhage. Because of high grade fever, we injected 150 microg granulocyte colony-stimulating factor (G-CSF) every 3 days postoperatively to prevent major infection. The combination of appropriate perioperative management and OPCAB yielded an effective result for a patient with severe hematological disorders causing pancytopenia.

Pancytopenia after removal of copper from total parenteral nutrition.

Patients who develop cholestatic jaundice during chronic total parenteral nutrition (TPN) can develop significant hematologic complications due to hypocupremia if copper supplementation is withheld. A 36-year-old female with short bowel syndrome developed progressive liver dysfunction 6 months after initiation of TPN. Trace elements were omitted from her TPN because of cholestasis and persistent hyperbilirubinemia. Despite chronic diarrhea, absorption of some dietary copper was anticipated from her oral diet. Fifteen months later, the patient became red cell transfusion dependent, and her neutrophil and platelet counts steadily declined. After 19 months of receiving TPN without trace elements, her serum copper level was 25 microLg/dL (normal: 70 to 155 microg/dL). Provision of trace elements for 2 months was associated with increased serum copper, neutrophil and platelet counts and independence from red cell transfusions. When the serum copper level reached 186 microg/dL, copper supplementation was discontinued. Over the next 3 months, serum copper level fell to 10 microg/dL, neutrophil and platelet counts fell precipitously, and red cell transfusions were resumed. Once again, copper, neutrophil and platelet levels promptly rebounded with parenteral copper supplementation. Although anemia and neutropenia are well-recognized hematologic consequences of copper deficiency, thrombocytopenia rarely has been reported. This is the first report of pancytopenia secondary to TPN-related copper deficiency in which the association was confirmed when hypocupremia recurred.

High-dose chemotherapy with autologous stem cell rescue in women with metastatic breast cancer with involved bone marrow: a role for peripheral blood progenitor transplant.

This retrospective analysis was done to determine the response rate and survival of women with metastatic breast cancer with bone marrow involvement treated with high-dose cyclophosphamide and thiotepa and peripheral progenitor cell rescue. Eligibility criteria included histologically-documented metastatic breast cancer and either stable disease, a partial response or a complete response to conventional dose chemotherapy. Due to bone marrow involvement, all patients received peripheral progenitor cell reinfusion. Purging of the stem cell product was not performed. Cyclophosphamide (CY) 7.5 gm/m2 total dose and thiotepa 675 mg/m2 total dose was used as the intensification regimen. Of 27 treated patients, 4 (14%) died of treatment-related toxicity. Three patients were in complete remission after induction chemotherapy and remained so after high-dose chemotherapy. Three patients converted from a partial response after induction to a complete response after transplant. This yielded a complete remission rate of 21%. Five of these six patients continue in CR at 5, 6, 11, 14, and 26 months post-transplant. Eight patients (29%) are alive with stable disease post transplant. Ten patients developed disease progression. Six patients died shortly after disease progression; however, four patients are alive with disease at 18, 26, 33, and 53 months post-transplant. The median time to treatment failure is 12 months. In women with metastatic breast cancer with bone marrow involvement, durable responses after high-dose chemotherapy are possible utilizing peripheral blood progenitor support rather than marrow purging.

Prediction of engraftment after peripheral blood stem cell transplantation by CD34-positive cells in grafts.

A total of 91 peripheral blood stem cell collections were performed in 26 children with various malignant tumors and peripheral blood stem cell transplantations (PBSCT) were performed in 15 of the children. There was a positive correlation between logarithm of total CD34+ cells/kg and logarithm of colony-forming unit-granulocyte macrophage (CFU-GM)/kg (r = 0.86). The time elapsed until the white blood cells (WBC) exceeded 1000/microL was related to both CFU-GM (r = 0.67) and CD34+ cell count (r = 0.60). The number of days elapsed until platelet count exceeded 5 x 10(4)/microL was not related to the logarithm of CFU-GM count/10(5) per kg transfused (r = 0.47), but was related to the logarithm of CD34+ cell counts/10(6) per kg transfused (r = 0.73). The number of days elapsed until the reticulocytes exceeded 10% was not related to the logarithm of CFU-GM count/10(5) per kg (r = 0.52), but was related to the logarithm of CD34+ cell counts/10(6) per kg transfused (r = 0.91). Although CD34+ cell counts correlated with the number of CFU-GM, bone marrow regeneration rates in three lineages were predicted more accurately by the number of CD34+ cells transfused than by the number of CFU-GM. These results suggest that measurement of the CD34+ cell count may be useful in predicting bone marrow regeneration rate after PBSCT.

Accelerated recovery of peripheral blood cell counts in mice transplanted with in vitro cytokine-expanded hematopoietic progenitors.

Interleukin 1 (IL-1) and interleukin 3 (IL-3) act synergistically in stimulating the growth of primitive hematopoietic progenitors. Murine bone marrow (BM) harvested 24 h after 5-fluorouracil (5-FU) administration (d1 5-FU BM) was stimulated with IL-1 and IL-3 to expand its progenitor pool during 7 days of suspension culture (delta-culture), and this in vitro expanded BM was compared to fresh d1 5-FU BM in its ability to reconstitute lethally irradiated or high-dose 5-FU-treated hosts. Transplantation with expanded delta-culture BM was found to dramatically shorten the period of cytopenia following lethal irradiation as compared to animals receiving d1 5-FU BM. Recipients of delta-cultured BM demonstrated accelerated recoveries of peripheral blood leukocytes, neutrophils, platelets, and erythrocytes. Furthermore, expansion of BM in vitro reduced the number of BM cells required for engraftment following lethal irradiation. Treatment of lethally irradiated mice with IL-1 and granulocyte colony-stimulating factor (G-CSF) following transplantation with delta-cultured BM or d1 5-FU BM further improved the recovery of neutrophils in these hosts. In conjunction with G-CSF post-transplantation cytokine therapy, high-dose 5-FU-treated mice transplanted with delta-cultured BM also demonstrated improved recovery kinetics of neutrophils and erythrocytes. Five and 10 weeks after BM transplantation, a decrease in the proliferative capacity of the earliest hematopoietic progenitors, detected in assays of primary and delta-culture generated-secondary high proliferative potential colony-forming cells (HPP-CFC), was found in all transplanted mice following a chemotherapy challenge with 5-FU. However, this impairment in the early progenitor/stem cell pool was not noticeably worsened by the expansion of BM in delta-cultures. The decrease in host hematopoietic proliferative potential associated with transplantation of limiting numbers of BM cells was not reversed over the 10 weeks of this study. The expansion of BM progenitor cells without loss of long-term proliferative potential may be of clinical importance in the fields of BM transplantation and gene therapy.

[Adjuvant parenteral nutrition in chemo- and radiotherapeutic measures in hematology]. / Adjuvante parenterale Ernährung bei chemo- und radiotherapeutischen Massnahmen in der Hämatologie.

The study investigates clinical nutrition of oncological patients as an essential adjuvant component in the whole therapeutical concept. The main subject of the study was the transfer of nutritional concepts which were developed in non-malignant diseases to oncological patients. We defined the homeostasis of patients by biochemical and biophysical parameters in blood (osmolality, Na, K, total protein, albumin, triglycerides, NEFA, glucose, lactate, creatinine, urea, total nitrogen, amino acids) and urine (volume, osmolality, Na, K, creatinine, urea, total nitrogen, and amino acids). Of special interest was the homeostasis of nitrogen, which was characterized by the loss of nitrogen and nitrogen balances. 10 patients with either transplantable panmyeolopathy or leukemia were investigated including a phase of immunsupressive treatment by total body radiation and cytostatic treatment. Parenteral nutrition was made with amino acids (1 g/kg/d), carbohydrates (6.5 g/kg/d) and fat (1 g/kg/d). During the preparatory phase nutrition was interrupted for two consecutive days because high amounts of electrolyte solution with up to 6 1/day were needed to protect the kidney. The period of investigation covered the complete period of treatment which endured up to three months. The essential result was the achievement of a constant body weight which decreased drastically under the conventional treatment without optimized nutrition. The homeostasis remained unchanged inspite of the fact that great changes occurred individually. Nitrogen balance and nitrogen loss demonstrate the strong influence of immun-suppresive treatment with N-losses of up to 20 g per day.(ABSTRACT TRUNCATED AT 250 WORDS)