| Key Question | Study Design | Risk of Bias | Consistency | Directness | Precision | Strength of Association | Overall Grade/Conclusion |
|---|---|---|---|---|---|---|---|
| What is the comparative effectiveness and harms of HSCT in the treatment of Farber's disease compared to symptom management and the natural history of the disease? Key outcomes are overall survival for the rapidly progressive form and neurocognitive and neurodevelopmental outcomes for the slowly progressive form. | Rapid progression: Type 1: 1 case report and 1 case series Slow progression: Type 2/3: 2 case series | Rapid progression: High Slow progression: High | Rapid progression: The evidence is inconsistent Slow progression: The evidence is consistent. | The outcomes reported are direct. | Rapid progression: The evidence is imprecise. Slow progression: Precise | Rapid progression: Not applicable for Type I Farber's disease. Slow progression: The strength of association is strong for Type 2/3 Farber's disease. | The body of evidence on overall survival with single HSCT compared to symptom management or natural history of the Type 1 form of Farber's disease is insufficient to draw conclusions. High strength evidence on number of subcutaneous nodules and number of joints with limited range of motion suggests a benefit with single HSCT compared to symptom management and the natural history of the Type 2/3 form of Farber's disease. 1 pt with Type 1 alive at 2.3 yrs followup with neurocognitive and neurodevelopmental decline. 1 pt with Type 1 dead at 6 mos post-HSCT from disease progression. All 5 pts with Type 2/3 alive at 0.7-1.3 yrs followup, with reduction in number of subcutaneous nodules and number of joints with limited range of motion. |
| What is the comparative effectiveness and harms of HSCT in the treatment of GM1 gangliosidosis compared to symptom management and natural history of the disease? Key outcomes are overall survival for the rapidly progressive form and neurocognitive and neurodevelopmental outcomes for the slowly progressive form. | Rapid progression: infantile form: 0 studies found Slow progression: juvenile form: 1 case report | Rapid progression: Not applicable Slow progression: High | Rapid progression: Not applicable Slow progression: Not applicable | The outcomes reported are direct. | Rapid progression: Not applicable Slow progression: Not applicable | Rapid progression: Not applicable Slow progression: Not applicable | Insufficient evidence for the infantile form of this disease. Insufficient evidence for the juvenile form of this disease. 1 pt alive at 7 yrs followup. Pt is wheelchair bound and has lost all language skills. |
| What is the comparative effectiveness and harms of HSCT in the treatment of Tay-Sachs disease compared to symptom management, substrate reduction therapy, and the natural history of the disease? Key outcomes are overall survival for the rapidly progressive form and neurocognitive and neurodevelopmental outcomes for the slowly progressive form. | Rapid progression: infantile form: 0 studies found Slow progression: juvenile form: 1 case report Unspecified progression: 1 case report and 1 case series | Rapid progression: Not applicable Slow progression: High Unspecified progression: High | Rapid progression: Not applicable Slow progression: Not applicable Unspecified progression: Not applicable | The comparisons are indirect as the evidence base utilizes two or more bodies of evidence to make comparisons. | Rapid progression: Not applicable Slow progression: Not applicable Unspecified progression: Not applicable | Rapid progression: Not applicable Slow progression: Not applicable Unspecified progression: Not applicable | Insufficient evidence for the infantile form of this disease. Insufficient evidence for the juvenile form of this disease. Insufficient evidence for the unspecified progression form of this disease. 1 pt with the juvenile form is alive at 2 yrs followup. Neurocognitive and neurodevelopmental decline is similar to untreated sibling. 2 pts with the juvenile form received substrate reduction therapy and were alive at 2 yrs followup. Both have declined neurocognitively and neurodevelopmentally. 1 pt with unspecified progression died 4.6 yrs post-HSCT of disease progression and the 2nd pt with unspecified progression was alive at 1.7 yrs post-transplant, but had regressed to a vegetative state. |
| What is the comparative effectiveness and harms of HSCT in the treatment of ceroid lipofuscinosis compared to symptom management and the natural history of the disease? Key outcomes are overall survival for the rapidly progressive form and neurocognitive and neurodevelopmental outcomes for the slowly progressive form. | Rapid progression: infantile form: 1 case series Slow progression: juvenile form: 0 studies found | Rapid progression: High Slow progression: Not applicable | Rapid progression: Consistent Slow progression: Not applicable | The outcomes reported are direct. | Rapid progression: The evidence is precise. Slow progression: Not applicable | Rapid progression (infantile): Not applicable due to lack of obvious effect size. Slow progression: Not applicable | Low strength evidence on neurocognitive outcomes suggests no benefit with single HSCT compared to symptom management and the natural history of the disease for the infantile form of ceroid lipofuscinosis. Insufficient evidence for the juvenile form of this disease. All 3 pts in case series are alive at 2-4 yrs followup. All 3 pts have neurocognitive decline, and are hypotonic and spastic. |
| What is the comparative effectiveness and harms of HSCT in the treatment of galactosialidosis compared to symptom management and the natural history of the disease? Key outcomes are overall survival for the rapidly progressive form and neurocognitive and neurodevelopmental outcomes for the slowly progressive form. | Unspecified progression: 1 case report | High | Not applicable | The outcomes reported are direct. | The evidence is imprecise. | Not applicable | The body of evidence on overall survival, neurocognitive and neurodevelopmental outcomes with HSCT compared to symptom management for galactosialidosis is insufficient to draw conclusions. This single case was part of a case series with several different diseases. Results were cumulative across all diseases and no data was available for the single galactosialidosis case 525 |
| What is the comparative effectiveness and harms of HSCT in the treatment of Sandhoff's disease compared to symptom management, substrate reduction therapy, and the natural history of the disease? Key outcomes are overall survival for the rapidly progressive form and neurocognitive and neurodevelopmental outcomes for the slowly progressive form. | Unspecified progression: 1 case report | High | Not applicable | The comparisons are indirect as the evidence base utilizes two or more bodies of evidence to make comparisons. | The evidence is imprecise. | Not applicable | The body of evidence on overall survival, neurocognitive and neurodevelopmental outcomes with HSCT compared to symptom management, substrate reduction therapy, and the natural history of the disease for Sandhoff's disease is insufficient to draw conclusions. The single case report was part of a case series with several diseases. The form of the disease was not specified and there were no neurocognitive or neurodevelopmental outcomes reported. 3 pts with the juvenile form received substrate reduction therapy and were alive at 2 yrs followup. They were stable neurocognitively, but 2 developed gait disturbance and 1 is wheelchair bound. |
From: Systematic Reviews
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