scholarly journals Excellent long-term survival after allogeneic marrow transplantation in patients with severe aplastic anemia

1997 ◽  
Vol 19 (12) ◽  
pp. 1191-1196 ◽  
Author(s):  
E Reiter ◽  
F Keil ◽  
S Brugger ◽  
P Kalhs ◽  
W Rabitsch ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Marrow Transplantation ◽  
Severe Aplastic Anemia ◽  
Term Survival ◽  
Long Term Survival ◽  
Allogeneic Marrow Transplantation ◽  
Allogeneic Marrow

Antithymocyte Immunoglobulin in Severe Aplastic Anemia and Bone Marrow Transplantation

1996 ◽  
Vol 30 (10) ◽  
pp. 1164-1174 ◽  
Author(s):  
Christine Colby ◽  
Cheryl A. Stoukides ◽  
Thomas R. Spitzer
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Marrow Transplantation ◽  
Severe Aplastic Anemia ◽  
Term Survival ◽  
Long Term Survival ◽  
Intensive Immunosuppressive Therapy

OBJECTIVE: To review antithymocyte immunoglobulin (ATG) and its current role in the treatment of severe aplastic anemia (SAA), focusing on ATG in immunosuppressive therapy compared with bone marrow transplantation (BMT). DATA SOURCES: A MEDLINE search (1966 to 1996) of English-language literature and human subjects pertaining to ATG and BMT therapy in SAA was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: The hallmark of SAA is pancytopenia and bone marrow hypoplasia. Although the etiology in a majority of cases remains unknown, current data implicate an immune-mediated destruction of stem cells. ATG is a potent immunosuppressive agent and has emerged as an important therapy for patients with SAA. The exact mechanism of immunosuppressive action is not fully understood, although ATG appears to disrupt cell-mediated immune responses resulting in inhibition or altered T-cell function. Numerous trials have evaluated the use of ATG both as monotherapy and in combination with other immunosuppressive agents. Treatment with ATG in SAA has demonstrated a 40–70% response rate. Data suggest that intensive immunosuppressive therapy with ATG in combination with cyclosporine may provide the optimal immunosuppressive treatment. Questions still remain concerning complications and long-term survival of the patients. Although more than a 2-year follow-up shows a decline in mortality, a plateau in the survival curve was not achieved. BMT is a potential treatment for SAA. Although there is a high initial mortality due to treatment-related toxicities, successful marrow engraftment provides a cure for SAA. Many patients (75–90%) experience long-term survival after allogenic BMT. Age, donor availability, and severity of disease limit the number of eligible patients. CONCLUSIONS: Due to excellent results with BMT, it has become the therapy of choice for selected patients with SAA. For patients who are not eligible for BMT, intensive immunosuppressive therapy with ATG and cyclosporine is recommended. Further study to better understand the pathogenesis of SAA and prevent treatment-related complications is essential to provide the best care to all patients.

High-Dose Cyclophosphamide in the Treatment of Children with Acquired Severe Aplastic Anemia Refractory to Conventional Immunosuppression.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3715-3715
Author(s):  
Jeffrey D. Hord ◽  
James A. Whitlock ◽  
Benjamin Carcamo ◽  
Ray C. Pais ◽  
Julie Blatt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Response Rate ◽  
Complete Response ◽  
Severe Aplastic Anemia ◽  
High Dose ◽  
Term Survival ◽  
Long Term Survival ◽  
Conventional Immunosuppression

Abstract Severe aplastic anemia (SAA), an illness characterized by the depletion of hematopoietic precursors within bone marrow leading to pancytopenia, has an overall mortality rate of >75% if left untreated. For children with human leukocyte antigen (HLA)-identical sibling donors, the treatment of choice for acquired SAA is allogeneic bone marrow transplant (BMT) with long-term survival of 70%–85%. For the 80% of children who lack suitable bone marrow donors, the standard treatment is immunosuppression with anti-thymocyte globulin (ATG), cyclosporine A (CSA), and often hematopoietic growth factors. Large series utilizing this immunosuppressive therapy have demonstrated a complete response rate of 60%–80%. When a patient does not have an HLA-identical sibling and fails to respond to conventional immunosuppression, options for further treatment are limited. One option is to pursue a matched unrelated donor (MUD) BMT, but matched donors are not available for all patients and long-term survival ranges between 20%– 60%. Treatment with high-dose cyclophosphamide is another option for refractory SAA patients that appears promising but has not been extensively studied in children. In 1999, a group of pediatric hematology centers joined together to study the use of high-dose cyclophosphamide for the treatment of children with acquired SAA not eligible for BMT and refractory to immunosuppression (Pediatric Aplastic Anemia Cooperative Trial #2). The goals of this study were to determine the response rate and toxicity associated with high-dose cyclophosphamide in children with refractory SAA. Between 10/1/99 and 6/3/02, 6 patients from 6 different centers were enrolled and received 4 days of intravenous cyclophosphamide (45 mg/kg/day), MESNA, and GM-CSF (250 mcg/m2/day SC) post-cyclophosphamide. The patient population consisted of 4 males and 2 females ranging in age from 2 to 18 years. The interval between diagnosis of SAA and cyclophosphamide treatment ranged from 8 to 88 months. All had failed to respond to earlier treatment with ATG and CSA. Twelve months following cyclophosphamide, there was 1 complete response (transfusion independent and normal blood counts), 1 partial response (transfusion independent but with moderate pancytopenia), 2 infectious deaths without recovery of blood counts, and 1 failure to respond. One patient was removed from the study before response could be assessed. High-dose cyclophosphamide in this population was associated with significant toxicity as 2 patients developed disseminated fungal infections within 30 days of starting therapy leading to death at day 18 in one. Another patient experienced grade 3 gingivitis/stomatitis lasting about 30 days. In summary, high-dose cyclophosphamide can lead to marrow recovery in some children with refractory SAA but is associated with the potential for life-threatening infectious complications, especially with fungus.

Marked Improvement in Short- and Long-Term Survival in Severe Aplastic Anemia Patients Treated with Immunosuppression in the Past 18 Years.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1698-1698
Author(s):  
Phillip Scheinberg ◽  
Colin O. Wu ◽  
Olga Nunez ◽  
Neal S. Young
Keyword(s):  
Supportive Care ◽  
Aplastic Anemia ◽  
Response Rate ◽  
Severe Aplastic Anemia ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Survival ◽  
Allogeneic Hsct ◽  
Short And Long Term

Abstract Forty years ago severe aplastic anemia (SAA) was almost universally fatal disease, but now most patients can be successfully treated with hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). Since the majority of patients are not suitable candidates for allogeneic HSCT from a histocompatible sibling, IST is usually the treatment of choice. From the introduction of the standard anti-thymocyte globulin (ATG) + cyclosporine (CsA) regimen in the 1980s, the hematologic response rate has been 60–70% despite efforts to improve on the ATG+CsA platform. Across many protocols, there is a strong link between response to IST and survival. We examined short and long term survival of patients who were treated with initial IST at the Clinical Center of the National Institutes of Health from 1989 to 2006; a total of 372 patients were analyzed in 3 separate cohorts: those who received IST from 1989–1995; 1996–2001 and 2002–2006. Thirty-two deaths occurred within the 6-months period of IST with 15 being attributed to a fungal infection. The distribution of early deaths (< 6 months) in relation to the different time periods were 15% (1989–1995); 9% (1996–2001); and 5% (2002–2006) (p = 0.003). Survival beyond 6 months also improved (1989–1995 and 2002–2006, 65% vs. 85%, respectively; p < 0.01). Surprisingly, the survival benefit was most striking among patients who did not respond to IST at 6 months. Among the total 116 non-responders, the number of patients who received a second course of IST was 0% (1989–1995), 37% (1996–2001) and 51% (2002–2006); those who underwent HSCT were 19% (1989–1995), 23% (1996–2001) and 18% (2002–2006); and those who did not receive a second course of IST or HSCT were 83% (1989–1995), 29% (1996–2001) and 11% (2002–2006). We draw two major conclusions from our data analysis. First, improvement in short term survival over the last two decades is most likely due to advances in supportive care, as the response rate to horse ATG + CsA has remained largely unchanged during the same time period. The marked decline in deaths due to invasive Aspergillosis infection suggests that the introduction of effective and relatively nontoxic antifungal drugs is of prime importance (e.g., voriconazole in 2002 and caspofungin in 2004). Second, the utilization of secondary therapies--a repeat course of IST and allogeneic HSCT for older adults and matched unrelated transplants for younger individuals--have salvaged patients who are primary ATG-failures. The advances in supportive care also impact long term survival in those who receive salvage therapies and in those who fail repeated courses of IST and are not suitable candidates for HSCT, who now can be adequately maintained on growth factor and transfusion support, often for years. Current survival rates in SAA should be weighed when in considering treatment algorithms for patients who fail initial IST.

scholarly journals Aplastic anemia treated by allogeneic bone marrow transplantation: a report on 49 new cases from Seattle

Blood ◽  
1976 ◽  
Vol 48 (6) ◽  
pp. 817-841 ◽  
Author(s):  
R Storb ◽  
ED Thomas ◽  
PL Weiden ◽  
CD Buckner ◽  
RA Clift ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Graft Rejection ◽  
Marrow Transplantation ◽  
Fungal Infections ◽  
Allogeneic Bone Marrow Transplantation ◽  
Severe Aplastic Anemia ◽  
Allogeneic Bone ◽  
Marrow Graft ◽  
Term Survival ◽  
Total Body

Forty-nine patients with severe aplastic anemia, 33 due to unknown cause, 11 drug or chemical related, 2 associated with hepatitis, 1 with paroxysmal nocturnal hemoglobinuria, and 2 possibly associated with Fanconi syndrome did not show recovery after 0.5–96 (median 2) mo of conventional therapy. Twenty-two were infected and 21 were refractory to random platelet transfusions at the time of admission. All were given marrow grafts from HLA-identical siblings. Forty-five were conditioned for grafting by cyclophosphamide (CY), 50 mg/kg on each of 4 successive days, and four by 1000 rad total body irradiation. All were given intermittent methotrexate therapy within the first 100 days of grafting to modify graft-versus-host disease (GVHD). Three patients died from infection too early to evaluate (days 1–8). Forty-six had marrow engraftment. Of these, 20 are surviving with good peripheral blood counts between 186 and 999 days, and 18 have returned to normal activities. Chronic GCHD is a problem in five. Twelve patients died of infection following rejection of the marrow graft. Twelve patients died with bacterial or fungal infections or interstitial pneumonia and active GVHD or soon following resolution of GVHD. Two patients died with marrow engraftment and no GVHD, one with an interstitial, and the other with a bacterial pneumonia. Thirty-six patients who had received random donor blood transfusions were randomly assigned to receive either CY or procarbazine-antithymocyte globulin-CY as conditioning regimens to test whether the incidence of graft rejection could be decreased. There was no difference in the incidence of graft rejection between the two regimens. In 13 patients with rejection, second transplants were attempted either with the original marrow donor (9 patients) or another HLA-identical sibling (4 patients). Three of these transplants were not evaluable, seven were unsuccessful and three were successful with only one of the three surviving for more than 468 days. In conclusion, the long-term survival of 41% of the patients in the present study is similar to that achieved in our first 24 patients, and confirms the importance of marrow transplantation for the treatment of severe aplastic anemia. Marrow graft rejection, GVHD, and infections continue to be the major causes of failure.

scholarly journals Severe aplastic anemia: allogeneic bone marrow transplantation as first-line treatment

2018 ◽  
Vol 2 (15) ◽  
pp. 2020-2028 ◽  
Author(s):  
George E. Georges ◽  
Kris Doney ◽  
Rainer Storb
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Marrow Transplantation ◽  
Severe Aplastic Anemia ◽  
Unrelated Donor ◽  
Line Treatment ◽  
First Line ◽  
Matched Unrelated Donor ◽  
First Line Treatment

Abstract Treatment of severe aplastic anemia has improved significantly over the past 4 decades. This review will summarize the key areas of progress in the use of allogeneic hematopoietic cell transplantation and nontransplant immunosuppressive therapy (IST) for the treatment of aplastic anemia and then summarize the recommendations for first-line treatment. Based on recent data, we argue that guidelines for the initial treatment of patients with newly diagnosed severe aplastic anemia require revision. At the time of diagnosis, before beginning treatment, HLA typing should be done to identify a marrow donor among family members or in the unrelated donor registries, and a marrow transplant should be considered first-line therapy. The priority order of donor source for bone marrow transplantation is: (1) HLA-identical sibling, (2) HLA-matched unrelated donor, and (3) HLA-haploidentical donor if an HLA-matched unrelated donor is not rapidly available. Each of these donor marrow sources may be preferable to nontransplant IST. We make this recommendation because of the long-term persistent risk for disease relapse and secondary myelodysplastic syndrome or acute myeloid leukemia with the use of nontransplant IST for patients with aplastic anemia. In contrast, marrow transplantation is associated with high cure rates of aplastic anemia and a relatively low risk for graft-versus-host disease, with many patients now living for decades without the risk for disease recurrence or the development of clonal disorders. Implementation of this first-line treatment strategy will provide patients with severe aplastic anemia the best chance of long-term disease-free survival.

scholarly journals Hematopoiesis in Long-Term Survival Following Supralethal Irradiation and Bone Marrow Transplantation in Dogs

Blood ◽  
1968 ◽  
Vol 32 (6) ◽  
pp. 895-907 ◽  
Author(s):  
J. L. CHERTKOV ◽  
M. N. NOVIKOVA ◽  
N. M. NEMENOVA ◽  
V. N. MALANINA
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Term Survival ◽  
Long Term Survival

scholarly journals Allogeneic marrow grafting for treatment of aplastic anemia: a follow- up on long-term survivors

Blood ◽  
1976 ◽  
Vol 48 (4) ◽  
pp. 485-490 ◽  
Author(s):  
R Storb ◽  
ED Thomas ◽  
CD Buckner ◽  
RA Clift ◽  
A Fefer ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Well Being ◽  
Severe Aplastic Anemia ◽  
Full Time ◽  
Graft Versus Host ◽  
Full Time Employment ◽  
Long Term Survivors ◽  
Allogeneic Marrow

Abstract Eleven of twenty-four patients with severe aplastic anemia given marrow grafts from HLA-identical siblings between October 1970 and March 1973 are alive with normal marrow function and continued evidence of engraftment 3–5 yr later. Ten have been leading normal lives with no immunosuppressive or other drug therapy since day 100 postgrafting. One has had chronic graft-versus-host disease of the skin which is now slowly improving with no therapy. He returned to full-time employment in the summer of 1975. The long-term well-being of almost half of our initial patients emphasizes the importance of marrow transplantation for the treatment of severe aplastic anemia.

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