Delayed hematopoietic recovery after auto-SCT in patients receiving arsenic trioxide-based therapy for acute promyelocytic leukemia: a multi-center analysis.

A potential link between arsenic (ATO)-based therapy and delayed hematopoietic recovery after autologous hematopoietic SCT (HSCT) for acute promyelocytic leukemia (APL) has previously been reported. We retrospectively reviewed the clinical histories of 58 patients undergoing autologous HSCT for APL at 21 institutions in the United States and Japan. Thirty-three (56%) of the patients received ATO-based therapy prior to stem cell collection. Delayed neutrophil engraftment occurred in 10 patients (17%): 9 of the 10 patients (90%) received prior ATO (representing 27% of all ATO-treated patients), compared with 1 of the 10 patients (10%) not previously treated with ATO (representing 4% of all ATO-naïve patients; P<0.001). Compared with ATO-naïve patients, ATO-treated patients experienced significantly longer times to ANC recovery (median 12 days vs 9 days, P<0.001). In multivariate analysis, the only significant independent predictor of delayed neutrophil engraftment was prior treatment with ATO (hazard ratio 4.87; P<0.001). Of the available stem cell aliquots from APL patients, the median viable post-thaw CD34+ cell recovery was significantly lower than that of cryopreserved autologous stem cell products from patients with non-APL AML. Our findings suggest that ATO exposure prior to CD34+ cell harvest has deleterious effects on hematopoietic recovery after autologous HSCT.

Auto-SCT for AML in second remission: CALGB study 9620.

We studied the feasibility and efficacy of a two-step approach to Auto-SCT for patients with AML in second remission. Step 1 consisted of consolidation chemotherapy using cytarabine 2000 mg/m(2) i.v. every 12 h for 4 days plus etoposide 40 mg/kg total dose by continuous i.v. infusion over the same 4 days. PBSC were collected after G-CSF stimulation during recovery from this chemotherapy. Step 2, auto-SCT, used a preparative regimen of oral BU 16 mg/kg over 4 days followed by etoposide 60 mg/kg i.v. Of the 50 patients entered on Step 1, two died from treatment complications, and seven failed to proceed to transplantation. A median CD34+ cell dose of 5.9 x 10(6)/kg was collected in a median of three collections. With a median follow-up of 8.2 years, 5-year disease-free survival (DFS) is 28%. The most important prognostic factor was cytogenetics, with acute promyelocytic leukemia (APL) patients having a 5-year DFS of 67% compared with 16% for others. We conclude that this two-step approach to autologous transplantation produces good CD34+ mobilization and that this approach has cured some patients. Results in patients with APL are especially promising.

Impact of intensive PBSC mobilization therapy on outcomes following auto-SCT for non-Hodgkin's lymphoma.

The best method to mobilize PBSCs in patients with non-Hodgkin's Lymphoma (NHL) is uncertain. We hypothesized that PBSC mobilization using an intensive chemotherapy regimen would improve outcomes after autologous hematopoietic stem cell transplantation (ASCT) in NHL patients at high risk for relapse. Fifty NHL patients were prospectively allocated to intense mobilization with high-dose etoposide plus either high-dose cytarabine or CY if they were 'high risk' for relapse, whereas 30 patients were allocated to nonintense mobilization with CY if they were 'standard risk' (all patients, +/-rituximab). All intensely mobilized patients were hospitalized compared with one-third of nonintensely mobilized patients. The EFS after ASCT was the same between the two groups, but overall survival (OS) was better for intensely mobilized patients (<0.01), including the diffuse large B-cell subgroup (P<0.04). We conclude that the intense mobilization of PBSCs in patients with NHL is more efficient than nonintense mobilization, but with greater toxicity. The equalization of EFS and superiority of OS in patients intensely mobilized to those nonintensely mobilized suggests that a treatment strategy using intensive chemotherapy for mobilization may be improving NHL outcomes after ASCT.

Autologous stem cell transplantation for advanced acute myeloid leukemia.

We studied the efficacy of a two-step approach to autologous stem cell transplantation for patients with advanced acute myeloid leukemia. Step 1 consisted of consolidation chemotherapy using cytarabine 2000 mg/m(2) twice daily for 4 days plus etoposide 40 mg/kg by continuous infusion over the same 4 days. Peripheral blood stem cells were collected under granulocyte colony-stimulating factor (G-CSF) stimulation during recovery from this chemotherapy. Step 2, autologous stem cell transplantation, utilized the preparative regimen of oral busulfan 16 mg/kg followed by etoposide 60 mg/kg i.v. During step 1, there were no treatment-related deaths among 28 patients, but two patients did not proceed to transplantation because of failure of mobilization. A median CD34+ dose (x10(6)/kg) of 13.6 was collected. Of 26 patients undergoing autologous transplant, there was one treatment-related death and 12 relapses. With a median follow-up of 5.4 years, 5 year event-free survival (EFS) of all patients entered is 54%. The most important prognostic factor was cytogenetic changes. All seven patients with t(15,17) remained in long-term remission whereas EFS for other patients was 38%. We conclude that this two-step approach to autologous transplantation produces excellent stem cell yields, allows a high percentage of patients to receive the intended therapy, and provides effective treatment.

High-dose chemotherapy and hematopoietic stem cell rescue for breast cancer: experience in California.

The role of high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell rescue in breast cancer is still controversial. We analyzed the outcomes of 1111 consecutive patients with histologically proven breast cancer who underwent HDCT at 5 major California medical centers. The overall treatment-related mortality (TRM) was 2.3%. TRM was not influenced by disease stage or the HDCT regimen delivered, but it was influenced by hematopoietic graft source. The TRM was 6.1% when bone marrow with or without blood stem cells was used, but only 1.4% when blood stem cells alone were used (P < .001). With a median follow-up of 2.8 years (range, 0.1-8.2 years) after HDCT and autologous hematopoietic stem cell rescue, the estimated 5-year event-free survival (EFS) and overall survival (OS) for stage II/IIIA patients with > or =10 involved axillary lymph nodes were 67% and 76%, respectively. Patients with metastatic breast cancer (MBC) (median follow-up, 1.9 years [range, 0.03-8.3 years]) achieving a complete response (CR) to conventional-dose chemotherapy or rendered to a "no evidence of disease" status before HDCT had significantly better estimated 5-year EFS and OS (28% and 57%, respectively) than those achieving a partial response before HDCT (19% and 27%, respectively; P < or = .0001). Our data suggest that HDCT with hematopoietic stem cell rescue is safe and can be beneficial to patients with high-risk primary breast cancer and for those with MBC achieving CR/no evidence of disease.

High-dose chemotherapy (CTM) for breast cancer.

We designed and implemented a new mitoxantrone-based high-dose chemotherapy regimen to minimize pulmonary injury (seen in carmustine-based regimens) in patients with breast cancer. One hundred and ninety-one breast cancer patients (99 stage II/IIIA; 27 stage IIIB; 65 stage IV responsive to conventional-dose chemotherapy) were treated with high-dose chemotherapy (CTM) delivered over 4 days (cyclophosphamide (6 g/m2), thiotepa (600 mg/m2), and mitoxantrone (24-60 mg/m2)) followed by autologous hematopoietic stem cell rescue. Stage II/III patients received chest wall radiation and tamoxifen (if hormone-receptor positive) after CTM. The 5-year event-free survival (EFS) for stage II/IIIA patients with 10 or more involved axillary lymph nodes (n = 80) was 62 +/- 12%. Hormone receptor-positive patients with 10 or more nodes did significantly better than negative patients. The EFS for stage IIIB patients at 5 years was 44 +/- 19%; for stage IV patients at 5 years was 17 +/- 10%. Stage IV patients achieving complete response in viscera and/or soft tissue prior to CTM did significantly better than those achieving a partial response. There were six (3%) treatment-related deaths including two due to diffuse alveolar hemorrhage. There were no episodes of delayed interstitial pneumonitis. There were six severe cardiac events in 91 patients (6.6%) but none after instituting mitoxantrone dose-adjustment in the final 100 patients. We conclude that CTM is associated with a low treatment-related mortality and little pulmonary toxicity. CTM produces excellent outcomes in stage II/IIIA patients with 10 or more involved axillary lymph nodes.

Autologous stem cell transplantation for acute myeloid leukemia in first remission.

We studied the feasibility, toxicity, and efficacy of a 2-step approach to autologous stem cell transplantation for patients with acute myeloid leukemia in first remission. Step 1 consisted of consolidation chemotherapy including cytarabine 2000 mg/m2 twice daily for 4 days concurrent with etoposide 40 mg/kg by continuous infusion over 4 days. During the recovery from this chemotherapy, peripheral blood stem cells were collected under granulocyte colony-stimulating factor stimulation. Step 2, autologous stem cell transplantation, involved the preparative regimen of busulfan 16 mg/kg followed by etoposide 60 mg/kg and reinfusion of unpurged peripheral blood stem cells. A total of 128 patients were treated. During step 1, there was 1 treatment-related death. A median CD34+ cell dose of 14 (x10(6)/kg) was collected in 3 aphereses. Ten patients suffered relapse before transplantation, and 117 patients (91%) proceeded to transplantation. During step 2, there were 2 treatment-related deaths, and 35 patients subsequently suffered relapse. With median follow-up of 30 months, 5-year disease-free survival for all patients entered in the study is projected to be 55%. By cytogenetic risk group, 5-year disease-free survival is 73% for favorable-risk patients, 51% for intermediate-risk patients, and 0% for poor-risk patients. We conclude that this 2-step approach to autologous transplantation produces excellent stem cell yields and allows a high percentage of patients to receive the intended therapy. Preliminary efficacy analysis is very encouraging, with outcomes that appear superior to those of conventional chemotherapy.

Autologous bone marrow transplantation for acute myeloid leukemia using 4-hydroperoxycyclophosphamide-purged bone marrow and the busulfan/etoposide preparative regimen: a follow-up report.

We studied the use of autologous bone marrow transplantation (ABMT) as treatment for acute myeloid leukemia (AML) in adults up to age 60. We used a preparative regimen of busulfan 16 mg/kg plus etoposide 60 mg/kg and bone marrow purged with 100 microg/ml of 4-hydroperoxycyclophosphamide (4HC). We treated 50 first remission patients; there were two treatment-related deaths and 13 relapses. With median follow-up of 6.8 years (minimum 4.5) disease-free survival (DFS) is 70%, relapse rate 27% and overall survival 72%. Patients with favorable cytogenetics had DFS 78% and relapse 18% whereas unfavorable patients had DFS 63% and relapse rate 35%. For 25 patients in second or third remission there were five treatment-related deaths and seven relapses. DFS is 52% and relapse rate 35%. None of six patients with primary refractory AML had long-term disease control. These data support the use of ABMT with an intensive preparative regimen and purged bone marrow as a highly effective treatment for adults with AML.

Successful immunomodulation with intravenous gamma globulin and cyclophosphamide in an alloimmunized heart transplant recipient.

A highly human leukocyte antigen-sensitized heart transplant candidate underwent immunomodulation with intravenous gamma globulin and cyclophosphamide. His panel reactive antibody screen fell from 64% to 14%. He underwent successful orthotopic heart transplantation with a histoincompatible, T-cell cross-match-negative heart without the development of hyperacute rejection. The combination of intravenous gamma globulin and cyclophosphamide may be a simple and effective means to overcome the human leukocyte antigen-barrier in sensitized heart transplant candidates.

High-dose cytarabine dose modification reduces the incidence of neurotoxicity in patients with renal insufficiency.

PURPOSE: To determine the impact of high-dose cytarabine (ARA-C) (HDAC) dose modification, based on renal function, on the incidence of neurotoxicity (NT). PATIENTS AND METHODS: We retrospectively analyzed the records of 256 patients treated with HDAC (> or = 2.0 g/m2 per dose) for acute myelogenous leukemia (AML) at the University of California, San Francisco (UCSF). From 1985 to 1994, a total of 358 cycles of HDAC were administered, using either a twice-daily schedule (n = 208) or a once-daily regimen (n = 48). In 1989, a dose-modification algorithm was initiated at our institution, which reduced ARA-C doses in the setting of renal insufficiency (RI). For patients with a serum creatinine (Cr) level of 1.5 to 1.9 mg/dL during treatment, or an increase in Cr during treatment (deltaCr) of 0.5 to 1.2 mg/dL, ARA-C was decreased to 1 g/m2 per dose. For patients with a Cr > or = 2.0 mg/dL or a deltaCr greater 1.2 mg/dL, the dose was reduced to 0.1 g/m2/d. RESULTS: Overall, the incidence of NT was 16% (34 of 208) for patients treated with twice-daily HDAC and 0% (none of 48) for patients treated with daily HDAC (P = .003). NT occurred more often in patients treated on a twice-daily schedule with 3 g/m2 per dose compared with 2 g/m2 per dose (25% v 8%; P = .009). NT occurred in 55% of the twice-daily-treated patients with RI, compared with 7% of those with normal renal function (P = .00001). In patients with RI, NT occurred in none of 11 dose-modified cycles versus five of 11 (45%) total unmodified cycles (P = .01). None of 14 patients treated with once-daily HDAC given during RI developed NT, compared to 55% of patients (23 of 42) receiving twice-daily HDAC during RI (P = .009). By univariate analysis, NT was not associated with patient age or serum alkaline phosphatase, but NT was significantly increased in patients treated with twice-daily HDAC when the serum bilirubin was > or = 2.0 mg/dL compared with twice-daily HDAC given when the total bilirubin was less than 2.0 mg/dL (33% v 14%; P = .017). Multivariate analysis confirmed that RI was the most significant risk factor associated with the development of NT. CONCLUSION: HDAC NT is strongly associated with RI. The risk of HDAC NT can be reduced by the following: (1) routinely reducing the ARA-C dose from 3 to 2 g/m2 per dose; (2) modifying the ARA-C dose based on daily Cr values; and (3) administering HDAC on a once-daily rather than twice-daily schedule.

The role of endoscopic evaluation in patients with suspected intestinal graft-versus-host disease after allogeneic bone-marrow transplantation.

BACKGROUND AND STUDY AIMS: Previous reports have suggested that endoscopic evaluation, with histological and microbiological examination of biopsied tissue, is required to diagnose gastrointestinal disease accurately in patients after allogeneic bone-marrow transplantation. We sought to further define the usefulness, yield, and sensitivity of endoscopic tissue biopsy in this patient population. PATIENTS AND METHODS: A retrospective review of the clinical, endoscopic, histological, and microbiological data was obtained during the evaluation and treatment of 61 distinct episodes of unexplained gastrointestinal complaints in 37 adult allogeneic bone-marrow transplant recipients over six years at our institution. RESULTS: Acute gastrointestinal graft-versus-host disease was found in 12 of the 61 episodes (20%). Gastrointestinal infections were found in 14 of the 61 episodes (23%); there were Herpesvirus infections (n = 8) and fungal infections (n = 9). Patients with and without graft-versus-host disease were similar in terms of their age, sex, underlying illness, clinical symptoms and signs, physical examination, laboratory values, and endoscopic findings. Small-bowel biopsy had a sensitivity of 90% for detecting the pathological changes of acute intestinal graft-versus-host disease in this series. CONCLUSION: A high percentage of patients with gastrointestinal complaints after allogeneic bone-marrow transplantation have acute gastrointestinal graft-versus-host disease, or an opportunistic infection. Gastrointestinal graft-versus-host disease cannot be accurately diagnosed from its clinical presentation. Endoscopic small-bowel biopsy is an essential tool in evaluating this patient population.

Delayed engraftment of 4-hydroperoxycyclophosphamide-purged autologous bone marrow after induction treatment containing mitoxantrone for acute myelogenous leukemia.

We have previously documented that adults with de novo acute myelogenous leukemia (AML) who are induced into first complete remission with mitoxantrone and high-dose cytarabine are more likely than those induced with daunorubicin and high-dose cytarabine to develop a bone marrow injury pattern with delayed cytopenias after achieving initial complete remission, a phenomenon we have termed post-remission cytopenia syndrome. We therefore retrospectively compared the engraftment kinetics of mitoxantrone and daunorubicin patients following 4-hydroperoxycyclophosphamide (4HC) purged autologous bone marrow transplant (ABMT) with busulfan-etoposide conditioning. Despite equivalent graft colony forming units granulocyte macrophage (CFU-GM), mitoxantrone patients (n = 13) took a median 7 weeks longer to achieve 1.0 x 10(9)/l granulocytes, 5 weeks longer to achieve platelet transfusion independence, and 10 weeks longer to achieve red blood cell transfusion independence, and required more platelet transfusions (P = 0.008), than daunorubicin patients (n = 13). Patients experiencing the post-remission cytopenia syndrome (n = 11) had significantly slower engraftment than those not experiencing the syndrome (n = 15; P < or = 0.04). Two mitoxantrone and five daunorubicin patients have relapsed after ABMT (P = 0.38). We conclude that the type of induction chemotherapy used in untreated adults with de novo AML can influence subsequent engraftment after 4HC-purged ABMT. We believe that mitoxantrone combined with high-dose cytarabine should be avoided as induction chemotherapy in patients for whom 4HC-purged ABMT is planned.

Post-remission cytopenias following intense induction chemotherapy for acute myeloid leukemia.

Forty-five patients with untreated, de novo acute myeloid leukemia (AML) were treated with high-dose cytosine arabinoside (Ara-C) plus mitoxantrone or daunorubicin. Forty-two patients entered complete remission with recovery of normal blood counts. Seven of these patients were excluded from further analysis (two, early consolidation chemotherapy; four, early relapse; one, hypersplenism). Of the remaining 35 patients, 20 (57%) developed thrombocytopenia and anemia (with or without neutropenia) a median of 3 weeks after entering complete remission. Post-remission cytopenias were more common in patients receiving mitoxantrone (81%) compared to those receiving daunorubicin (37%; p < 0.003). The cytopenias lasted a median of 54 days. Four of five patients in whom the cytopenias did not recover received mitoxantrone. Leukemia relapse or myelodysplasia did not explain these cytopenias. Post-remission cytopenias resulted in a greater than 90-day delay or prevention of planned autologous bone marrow transplantation in 13 of 17 otherwise eligible patients. We conclude that post-remission cytopenias are common following blood count recovery in AML patients entering complete remission with high-dose Ara-C and mitoxantrone or daunorubicin. Post-remission cytopenias do not necessarily imply leukemia relapse.

Busulfan plus etoposide as a preparative regimen for autologous bone marrow transplantation for acute myelogenous leukemia: an update.

We have used a new preparative regimen prior to autologous bone marrow transplantation in patients in remission of acute myelogenous leukemia (AML). Sixty-two patients were treated with preparative chemotherapy consisting of 1 mg/kg of busulfan every 6 hours for 4 days (total dose 16 mg/kg) on days -7 to -4 followed by an intravenous infusion of 60 mg/kg of etoposide on day -3. Autologous bone marrow that had been purged with 4-hydroperoxycyclophosphamide was infused on day 0. Thirty-five of the treated patients were in first remission, 21 were in second or third remission, and six had primary refractory AML and required aggressive salvage regimens to achieve remission. Among patients in first remission, one treatment-related death and five relapses have occurred. With a median follow-up of 25 months, the actuarial relapse rate is 19% +/- 8% and the disease-free survival rate is 79% +/- 8% at 3 years. The 16 patients with favorable FAB subtypes (M3 or M4E0) showed an excellent response to this treatment protocol, with no relapses after median follow-up of 35 months. Among patients in second or third remission, there were five treatment-related deaths and five relapses. With a median follow-up of 41 months, the actuarial relapse rate is 30% +/- 11% and the disease-free survival rate is 52% +/- 11% at 3 years. Four of six primary refractory patients died during treatment and one remains in remission with short follow-up. These preliminary data indicate that aggressive preparative regimens followed by the infusion of purged autologous bone marrow may be a promising approach to improving the clinical outcome of adult patients with AML.

Gallium-avid thymic hyperplasia in an adult after chemotherapy for Hodgkin disease.

This article presents the case of a 22-year-old patient with treated Hodgkin disease (HD) who had mediastinal widening on computed tomography scan after chemotherapy. This mass was gallium avid. These findings were explained by histologically documented benign thymic hyperplasia, the first such case reported in an adult with HD, to the knowledge of the authors. The literature on thymic hyperplasia after chemotherapy is reviewed.

Cyclosporine-induced hemolytic uremic syndrome in a heart transplant recipient.

We report a case of hemolytic uremic syndrome associated with the use of cyclosporine in a heart transplant recipient. The patient manifested many classic signs and symptoms of hemolytic uremic syndrome, and a diagnosis was confirmed by kidney biopsy. Treatment with plasma exchange was effective in halting the hemolysis, but renal function failed to improve. Rechallenge with cyclosporine caused recurrence of microangiopathic hemolysis. Because of concerns regarding allograft rejection, an experimental immunosuppressive agent, RS-61443, was used that was effective in controlling rejection and was not associated with recurrence of hemolytic uremic syndrome.

Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen.

We have studied the use of a new preparative regimen for the treatment of patients in remission of acute myeloid leukemia (AML) with autologous bone marrow transplantation. Chemotherapy consisted of busulfan 1 mg/kg every 6 hours for 4 days (total dose, 16 mg/kg) on days -7 through -4 followed by an intravenous infusion over 6 to 10 hours of etoposide 60 mg/kg on day -3. Autologous bone marrow, treated in vitro with 100 micrograms/mL of 4-hydroperoxycyclophosphamide, was infused on day 0. We have treated 58 patients up to the age of 60 years, 32 in first remission, 21 in second or third remission, and 5 with primary refractory AML unresponsive to high-dose Ara-C, but achieving remission with aggressive salvage regimens. Of the first remission patients, there has been 1 treatment related death and 5 relapses. With median follow-up of 22 months, the actuarial relapse rate is 22% +/- 9% and disease-free survival is 76% +/- 9% at 3 years. Patients with favorable French-American-British (FAB) subtypes (M3 or M4 EO) did especially well, with no relapses seen in 15 patients observed for a median of 30 months. Actuarial relapse rate at 3 years was 48% for first remission patients with less favorable FAB subtypes. Of patients in second or third remission, there were 5 treatment related deaths and 4 relapses. With median follow-up of 22 months, the actuarial relapse rate is 25% +/- 11% and disease-free survival is 56% +/- 11% at 3 years. Four of five primary refractory patients died during treatment and 1 remains in remission with short follow-up. These preliminary data are very encouraging and, if confirmed, support the use of autologous purged bone marrow transplantation using aggressive preparative regimens as one approach to improve the outcome of adults with AML.

Thrombotic microangiopathies in the 1980s: clinical features, response to treatment, and the impact of the human immunodeficiency virus epidemic.

We reviewed the medical records of 44 adults with 50 consecutive episodes of thrombotic thrombocytopenia purpura (TTP) or hemolytic uremic syndrome (HUS) seen at the University of California, San Francisco affiliated hospitals during the past decade. Patients were treated according to a uniform plan in which initial therapy included daily large volume plasmapheresis using fresh frozen plasma. Patients not responding completely to initial therapy were treated with a salvage regimen including splenectomy, dextran, and corticosteroids. At the time of diagnosis, the lactate dehydrogenase (LDH) was elevated in 98% of cases, with a median value of 1,208 U/L. Other clinical features were present inconsistently, and only 34% of "TTP" episodes involved the classic pentad of hemolytic anemia, thrombocytopenia, neurologic disorders, noninfectious fever, and renal impairment. Primary treatment with plasma exchange produced complete remission in 56% (27 of 48) of the episodes. Previously splenectomized patients uniformly responded to plasma therapy (12 of 12). In patients not responding completely to primary therapy, salvage splenectomy produced complete responses in 81% (13 of 16) of the cases. The pattern of clinical response to therapy was consistent, with initial resolution of neurologic dysfunction (median, 3 days) followed by normalization of LDH levels (5 days) and platelet count (7 days). Normalization of renal function occurred significantly later (15 days). Although short-term responses to plasma therapy in human immunodeficiency virus (HIV)-seropositive patients did not differ from other patients, no HIV-positive patient survived more than 2 years from diagnosis of thrombotic microangiopathy (TMA). We conclude that the diagnosis of TMA requires a high degree of clinical suspicion and that the diagnostic criteria should consist of microangiopathic hemolytic anemia, thrombocytopenia, and an elevated LDH. Initial therapy with plasma exchange leads to disease control in the majority of cases, but an optimal treatment strategy requires the use of alternative methods if initial remission is transient or not achieved. Salvage therapy with splenectomy, steroids, and dextran is highly effective in this setting.

Anemias of chronic disease in the aged: diagnosis and treatment.

The classic anemia of chronic disease is sideropenic and is the result of subacute or chronic inflammatory illness, including malignancy. Nonsideropenic anemias, by contrast, are the result of failure of vital organs or endocrine glands. The pathophysiology of these anemias is multifactorial, but underlying all of them is absolute or relative hypoerythropoietinemia. Therapy consists of treating the underlying illness and, if necessary, providing packed red blood cell transfusions. Some patients will respond to recombinant erythropoietin injections, which have been shown to result in improved hemoglobins and hematocrits and an enhanced quality of life.